nlmpubs.nlm.nih.gov/2014.05.nlmpubs.nlm.nih.gov.tar/nlmpubs.nlm.nih.gov/aids/adatabases/trials.txt

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PROG:

1
UNIQUE IDENTIFIER         NIH/00992
PROTOCOL ID NUMBERS       CC 97 C-0040
PROTOCOL TITLE            EPOCH (Etoposide, Prednisone, Vincristine,
                          Cyclophosphamide, and Doxorubicin)
                          Chemotherapy +/- IL-12 for Previously
                          Untreated and EPOCH Plus Rituximub for
                          Previously Treated Patients with
                          AIDS-Associated Lymphoma.
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Richard Little
GENERAL DESCRIPTION       PURPOSE: To investigate the toxicity and
                          activity of interleukin-12 (IL-12) following
                          chemotherapy with EPOCH (i.e., etoposide
                          [VP-16], prednisone, vincristine [VCR],
                          cyclophosphamide [CPM], and doxorubicin
                          [DOX]) or other chemotherapy in patients with
                          AIDS-associated non-Hodgkin's lymphoma that
                          is either untreated and newly diagnosed or
                          previously treated and recurrent, following 1
                          prior chemotherapy regimen. To examine the
                          effect of EPOCH and/or IL-12 on HIV-1 load,
                          CD4+ cell number, and TH1 and TH2 functional
                          CD4+ subtypes. To evaluate the toxicity and
                          activity of EPOCH in these patients. To
                          assess the molecular markers of drug
                          resistance (i.e., p53, p16, bcl-2, and MIB-1)
                          and lymphomagenesis (i.e., c-myc, EBV, and
                          HHV-8) in tumor tissue.
GENERAL DESCRIPTION       RATIONALE: It has been shown that infusional
                          chemotherapy with EPOCH is well tolerated and
                          active in the treatment of non-AIDS lymphoma.
                          Investigational studies suggest that the
                          three drugs found in EPOCH (VP-16, DOX, and
                          VCR) may be more effective and less toxic in
                          the treatment of non-Hodgkin's lymphoma when
                          administered as an infusion over 4 days than
                          when given by standard delivery methods.
                          Studies in lab animals suggest that IL-12 may
                          improve the immune function of T-cells,
                          helping them fight HIV infection, and may
                          also shrink certain tumors.
GENERAL DESCRIPTION       METHODOLOGY: Previously untreated patients
                          initially receive EPOCH chemotherapy, as
                          follows: Days 1-4: VP-16 plus DOX plus VCR as
                          a 96-hour continuous infusion. Days 1-5:
                          Prednisone daily. Day 5: CPM for Course 1
                          only. Days 6-19 (or until post nadir absolute
                          neutrophil count greater than 5,000
                          cells/mm3): G-CSF daily. Courses repeat every
                          3 weeks for a total of 6 courses. Patients
                          who achieve a complete response are
                          randomized to receive IL-12 biweekly for 12
                          weeks or no further therapy. Patients who
                          exhibit residual or progressive disease
                          following 6 courses of chemotherapy receive
                          IL-12 biweekly for 24 weeks. Previously
                          treated patients receive IL-12 biweekly,
                          beginning at least 21 days following the last
                          course of chemotherapy.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy, Immunotherapy, Drug toxicity, Viral
                          load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 43 patients. 18 previously
                          untreated patients (9 per arm). 25 previously
                          treated patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: Lymphoma, Non-Hodgkin.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: 97 C-0040C. T96-0036N
PROTOCOL DETAILS          STUDY DESIGN: Random Allocation
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Aggressive non-Hodgkin's lymphoma
                          (NHL) of any stage that has been
                          pathologically confirmed by the National
                          Cancer Institute (NCI). 2. HIV infection that
                          has been confirmed by NCI. 3. Measurable
                          disease. 4. A CD4 cell count greater than 100
                          cells/mm3 [AS PER AMENDMENT 2/27/98: Prior to
                          cytotoxic chemotherapy].
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3 Unless due to
                          tumor involvement in patients to be treated
                          with chemotherapy. Platelets >= 30,000 in
                          patients with idiopathic thrombocytopenic
                          purpura.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 100 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 Total bilirubin <= 3.7 mg/dL.
                          (direct bilirubin <= 0.2 mg/dL; indirect
                          bilirubin <= 3.5 mg/dL) if due to protease
                          inhibitor therapy.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2 x ULN ULN (Upper Limit of
                          Normal). <= 3 X ULN in patients to be treated
                          with ch
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2 x ULN <=3xULN in patients to
                          be treated with chemotherapy. <=6xULN in
                          patients on hyperalimentation.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 All patients required to
                          meet study criteria for either creatinine OR
                          creatinine clearance.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Concurrent
                          antiretroviral therapy at the discretion of
                          the principal investigator.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Approved antiretroviral
                          therapy required of all patients, beginning
                          at least 3 weeks prior to the start of IL-12.
                          (AS PER AMENDMENT 2/27/98: It is not
                          necessary to already be on antiretroviral
                          medications to enroll.).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of clinical heart failure. 2. History
                          of inflammatory bowel disease.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: IL-12.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Primary CNS lymphoma. 2. Leptomeningeal
                          metastases if patient is to receive IL-12. 3.
                          Symptomatic ischemic heart disease. 4. Active
                          gastrointestinal bleeding. 5. Uncontrolled
                          peptic ulcer disease. 6. Serious, underlying
                          medical condition or infection (other than
                          HIV) that precludes participation in study.
                          7. Clinically significant autoimmune disease.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0081  Etoposide
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0227  Prednisone
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0046  Vincristine sulfate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0048  Cyclophosphamide
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0047  Doxorubicin hydrochloride
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0259  Interleukin-12
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0086  Filgrastim
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 50 mg/m2 qd over 4
                          days (96h infusion). Drug 2: 60 mg/m2 qd for
                          5 days. Drug 3: 0.4 mg/m2 qd over 4 days (96h
                          infusion). Drug 4: Course 1: 375 mg/m2 on Day
                          5. Drug 5: 10 mg/m2 qd over 4 days (96h
                          infusion). Drug 6: Patients in complete
                          response: 300 ng/kg sq biw for 12 Patients
                          with disease: 300 ng/kg sq biw for 24 weeks.
                          Drug 7: 5 micrograms/kg/day SC Days 6-19 or
                          until the post nadiis > 5,000, whichever is
                          sooner
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 50 mg. Drug 2: 60 mg.
                          Drug 3: 0.4 mg/m2. Drug 5: 10 mg. Drug 7: 5
                          micrograms/kg/day
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Intravenous. Drug 4: Intravenous.
                          Drug 5: Intravenous. Drug 6: Subcutaneous
                          injection. Drug 7: Subcutaneous
OTHER TREATMENT INFO.     END POINT: Toxicity and efficacy of IL-12
                          following EPOCH or other chemotherapy, effect
                          of EPOCH and/or IL-12 on HIV parameters,
                          molecular markers of drug resistance.
SUPPORTING AGENCY         Natl Cancer Institute.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 991130.

2
UNIQUE IDENTIFIER         NIH/00989
PROTOCOL ID NUMBERS       NIAID ACTG 317
PROTOCOL TITLE            The Effect of Oral and Injectable
                          Contraceptives (Norethindrone/Ethinyl
                          Estradiol, Medroxyprogesterone Acetate) and
                          Gender on Plasma and Intracellular Zidovudine
                          Pharmacokinetics.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Francesca Aweeka
GENERAL DESCRIPTION       PURPOSE: [AS PER AMENDMENT 11/13/00: To
                          investigate differences in zidovudine (ZDV)
                          metabolism and intracellular pharmacokinetics
                          between male and female patients.] To
                          evaluate the potential effects of concomitant
                          oral contraceptives and intramuscularly
                          administered medroxyprogesterone acetate on
                          ZDV metabolism and intracellular
                          pharmacokinetics in women.
GENERAL DESCRIPTION       RATIONALE: Oral contraceptives have been
                          shown to substantially enhance the
                          glucuronidation of several compounds. One
                          study reported enhanced glucuronidation of
                          oxazepam, a compound that is conjugated via
                          the same UDP-glucuronyl transferase isozyme
                          responsible for ADV glucuronidation,
                          suggesting that ZDV metabolism may be altered
                          by concomitant oral contraceptive use. This
                          potential enhancement of ZDV metabolism by
                          oral contraceptives is expected to result in
                          decreased plasma levels of the parent
                          compound which may lead to diminished
                          clinical efficacy in women using these drugs.
                          It remains unclear whether the progesterone
                          and/or estrogen component of oral
                          contraceptives results in the observed
                          glucuronidation changes.
GENERAL DESCRIPTION       METHODOLOGY: This open-label, pharmacokinetic
                          trial is conducted in 2 steps. [AS PER
                          AMENDMENT 6/12/01: The Depo-Provera IM group
                          in Step 2 is filled. Female patients who
                          choose to participate in Step 2 may enroll
                          only in the Ortho-Novum 1/35 PO group.] [AS
                          PER AMENDMENT 11/13/00: Female patients may
                          choose to participate in Step 1 alone or both
                          Steps 1 and 2.] Male patients may participate
                          in Step 1 only as the control arm of the
                          study. In Step 1, patients are stratified by
                          sex; in Step 2, female patients are
                          stratified by their choice of contraception
                          (i.e., oral norethindrone/ethinyl estradiol
                          [Ortho-Novum 1/35] or injectable
                          medroxyprogesterone acetate [Depo-Provera]).
                          Step 1 (males and females): At entry, all
                          patients are randomized to receive ZDV either
                          orally or orally and intravenously (IV) on
                          Days 7 and 8. Female patients begin the study
                          (Day 0) between days 10-18 after the first
                          day of their last menstrual period (LMP)
                          (Cycle 1). At time of enrollment, female
                          patients [AS PER AMENDMENT 11/13/00: who plan
                          to participate in Step 2] choose the form of
                          birth control instituted in Step 2:
                          Depo-Provera or Ortho-Novum 1/35. Male
                          patients may enter Step 1 at any time.
                          Patients continue taking their other
                          pre-study antiretroviral drugs during Step 1.
                          [AS PER AMENDMENT 6/3/99: Patients taking
                          nelfinavir may participate only in the
                          Depo-Provera arm.] Days 0-6: All patients
                          receive oral ZDV. Day 7: Patients are
                          randomized to receive: Arm 1 (females): oral
                          ZDV for a total of 3 doses. Arm 2 (females):
                          ZDV IV, then ZDV orally for a total of 2 oral
                          doses. Arm 3 (males): control arm. Half of
                          the male patients receive ZDV as in Arm 1 and
                          the other male patients receive ZDV as in Arm
                          2. Day 8: Patients on all 3 arms receive the
                          alternate form of ZDV to that received on Day
                          7. Day 9: Female patients resume their
                          pre-study method of administration of ZDV.
                          Male patients conclude their participation in
                          the study on Day 8. Step 2 (females [AS PER
                          AMENDMENT 11/13/00: opting to participate in
                          Step 2]): At the onset of their second
                          menstrual period (Cycle 2) since starting
                          study, female patients start their choice of
                          Ortho-Novum 1/35 or intramuscularly
                          administered Depo-Provera [AS PER AMENDMENT
                          6/12/01: Enrollment for Depo-Provera is
                          closed]. Contraceptive therapy continues
                          throughout Step 2. Step 2 Days 0-6: Between
                          days 7-11 [AS PER AMENDMENT 6/3/99: Between
                          days 7-18] of the third menstrual cycle
                          (Cycle 3) since starting study, female
                          patients continue their pre-study
                          antiretroviral therapy (as done in Step 1)
                          and begin another course of ZDV standard
                          therapy 3 times daily. Days 7-8: Patients
                          receive the original method of administration
                          of ZDV (as randomized at study entry). Female
                          patients return for a final safety visit
                          within 1 week of completing study Day 8 of
                          Step 2.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Administration route
                          comparison, Combination drug therapy, Drug
                          interactions, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 42 patients. (Arm 1: 12
                          females) (Arm 2: 12 females) (Arm 3: 18
                          males).
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Males: 8 days.
                          Females: Approximately 3 months. [AS PER
                          AMENDMENT 11/13/00: Females participating in
                          Step 1 alone: 8 days. Females participating
                          in Steps 1 and 2: Approximately 3 months.].
PROTOCOL DETAILS          ACTUAL ACCRUAL: 37/42 010712.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6
PROTOCOL DETAILS          VERSION NUMBER & DATE: 4 (010612)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG 317
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Male and female
                          patients must have: HIV infection documented
                          by a licensed ELISA confirmed by a second
                          FDA-approved confirmatory test (e.g., Western
                          blot). Female patients must have: 1. Regular
                          menstrual cycles, defined as 25- to 35-day
                          intervals with usual amounts of bleeding.
                          NOTE: Postpartum patients are required to
                          have at least 1 menstrual period postpartum.
                          2. Normal gynecologic examination status
                          (includes Pap smear and age-indicated
                          mammography). [AS PER AMENDMENT 6/3/99:
                          Normal gynecologic examination as defined by
                          a normal age-indicated mammogram (i.e., for
                          women age 40 and above) and a normal pap
                          smear or a pap smear with low-grade changes
                          (human papilloma virus changes/CIN I or a
                          low-grade cervical dysplasia [SIL]) within 6
                          months prior to study entry.] [AS PER
                          AMENDMENT 11/13/00: Normal age-indicated
                          mammogram is required within 2 years prior to
                          study entry.] 3. Enter study between 10-18
                          days since the first day of patient's last
                          menstrual period (LMP). 4. Willing to begin
                          contraceptive use with either oral
                          contraceptives or Depo-Provera.
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 30 %.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min [AS PER
                          AMENDMENT 11/13/00].
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study Negative
                          pregnancy test within 14 days of study entry
                          Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: History of at
                          least 60 days or more cumulative ZDV therapy
                          alone or in a combination regimen of one of
                          the following: ZDV + 3TC, ZDV + ddI, ZDV +
                          ddC or ZDV + 3TC + indinavir, up to seven
                          days prior to study entry. [AS PER AMENDMENT
                          6/3/99: History of at least 60 days on stable
                          ZDV combination therapy comprising 1 of the
                          following: ZDV + 3TC (or Combivir); ZDV +
                          ddI; ZDV + ddC; ZDV + indinavir, or ZDV +
                          nelfinavir.].
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: [Allowed: AS PER
                          AMENDMENT 6/12/01: Trizivir. Patients
                          receiving Trizivir (fixed dose combination of
                          abacavir [ABC], 3TC, and ZDV) will be
                          required to have a prescription for ABC and
                          3TC during the ZDV pharmacokinetics portion
                          of the study (i.e., Days 0-8 for both Step 1
                          and Step 2).].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 45 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Male and female
                          patients with any of the following prior
                          conditions are excluded: 1. Intolerance to
                          600 mg/day ZDV, defined as any grade toxicity
                          which resulted in a permanent dose reduction
                          or termination of ZDV. 2. History of [AS PER
                          AMENDMENT 11/13/00: chronic] hypertension
                          (blood pressure above 140/90 mm Hg) ) [AS PER
                          AMENDMENT 11/13/00: is not an exclusion for
                          female patients participating in Step 1 alone
                          or male patients]. 3. History of
                          thrombophlebitis or pulmonary emboli [AS PER
                          AMENDMENT 11/13/00: is not an exclusion for
                          female patients participating in Step 1 alone
                          or male patients]. Female patients with any
                          of the following prior conditions are
                          excluded: 1. History of intolerance to oral
                          contraceptives for patients in the
                          Ortho-Novum 1/35 arm. 2. History of
                          intolerance to Depo-Provera for patients in
                          the Depo-Provera arm. [3. AS PER AMENDMENT
                          11/13/00: History of chronic hypertension
                          (blood pressure above 140/90 mm Hg) if
                          participating in Step 2. 4. History of
                          thrombophlebitis or pulmonary emboli if
                          participating in Step 2.].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Nonnucleoside
                          reverse transcriptase inhibitors. 2. Within 7
                          days prior to study entry [AS PER AMENDMENT
                          11/13/00: Within 7 days prior to or on
                          pharmacokinetic evaluation days]:
                          clarithromycin, ketoconazole, fluconazole,
                          trimethoprim, probenecid, rifampin, and
                          rifabutin. [3. AS PER AMENDMENT 6/12/2001:
                          Nelfinavir, for women enrolling in Step 2.]
                          Women: Oral contraceptives for 3 months or
                          Depo-Provera within 3 months [AS PER
                          AMENDMENT 11/13/00: 6 months] of study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Nonnucleoside reverse transcriptase
                          inhibitors [AS PER AMENDMENT 6/3/99: or other
                          antiretroviral drugs not specifically
                          permitted in this protocol]. 2. Drugs that
                          alter ZDV pharmacokinetics [AS PER AMENDMENT
                          11/13/00: are prohibited for 7 days prior to
                          and on pharmacokinetic evaluation days]:
                          clarithromycin, ketoconazole, fluconazole,
                          trimethoprim, probenecid, rifampin, and
                          rifabutin. [3. AS PER AMENDMENT 6/12/01:
                          Stavudine.].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with any of the
                          following symptoms and conditions are
                          excluded: Malignancy including Kaposi's
                          sarcoma.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Steps 1 and 2: Days
                          0 to 6: 200 mg po q 8 h. Days 7 to 8: 200 mg
                          po q 8 h for 3 doses or 200 mg IV over 1
                          hothen 200 mg po q 8h for 2 po doses
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Steps 1 and 2: Days 0
                          to 6: 600 mg. Days 7 to 8: 600 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral or IV
OTHER TREATMENT INFO.     TREATMENT DURATION: Males: 8 days. Females:
                          Approximately 3 months. [AS PER AMENDMENT
                          11/13/00: Females participating in Step 1
                          alone: 8 days. Females participating in Steps
                          1 and 2: Approximately 3 months.].
OTHER TREATMENT INFO.     END POINT: Pharmacokinetics.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patient or legal
                          guardian refuses further treatment and/or
                          follow-up evaluations. 2. Investigator
                          determines that further participation would
                          be detrimental to the patient's health or
                          well-being. 3. Patient fails to comply with
                          study requirements so as to cause harm to
                          self or seriously interfere with the validity
                          of the study results. 4. Patient requires
                          treatment with medications that are
                          disallowed while on the study. 5. Patient
                          requires ZDV dose modification during either
                          of the ZDV steady state periods. 6.
                          Pregnancy.
OTHER TREATMENT INFO.     MODIFICATION: Patients who require any dose
                          modification of ZDV during each of the steady
                          state periods will be removed from the study
                          and replaced by another patient. Toxicity
                          management and dose modification will be
                          completed per the approved drug labels for
                          both Ortho-Novum 1/35 and Depo-Provera.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                San Francisco AIDS Clinic / San Francisco Gen
                          Hosp 995 Potrero Ave / Building 80 / Ward 84
                          San Francisco, CA 941102859 Marc Gould
                          [phone] Recruiting 980121.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          010517.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Barbara
                          Longmire [phone] No longer recruiting
                          010627.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 001006.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Ross Hewitt
                          [phone] Recruiting 981028.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 990924.

3
UNIQUE IDENTIFIER         NIH/00967
PROTOCOL ID NUMBERS       NIAID ACTG 382
PROTOCOL TITLE            A Phase I/II, Open-Label, AUC-Controlled
                          Study to Determine the Pharmacokinetics,
                          Safety, Tolerability, and Antiviral Activity
                          of DMP 266 (Efavirenz) in Combination With
                          Nelfinavir in Children.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Courtney Fletcher
PROTOCOL CHAIRS           CO-CHAIR  Stuart Starr
GENERAL DESCRIPTION       PURPOSE: [AS PER AMENDMENT 5/26/98: Cohort
                          I:] To determine the dosing regimen and
                          safety profile of efavirenz (DMP 266, EFV) in
                          combination with nelfinavir (NFV) in
                          children. [AS PER AMENDMENT 5/26/98: Cohort
                          II: To define the pharmacokinetics and safety
                          of a liquid preparation of DMP 266 in
                          combination with NFV in infants and young
                          children.]
GENERAL DESCRIPTION       RATIONALE: The demonstrated antiviral
                          activity, tolerability, and pharmacokinetic
                          properties of DMP 266 and its utility in
                          combination with other agents make DMP 266 an
                          attractive agent for use in HIV-infected
                          pediatric patients. However, the tolerability
                          of DMP 266 in the pediatric population must
                          be evaluated, and appropriate dosing
                          instructions need to be developed. By
                          following the patients over time, the
                          antiviral activity of DMP 266-containing
                          regimens will be documented. Dosage
                          guidelines for children can then be developed
                          following analysis of the results.
GENERAL DESCRIPTION       METHODOLOGY: This is a 48-week [AS PER
                          AMENDMENT (APA) 12/21/98:104-week] [APA
                          5/8/00: 208-week] study. It is designed to
                          minimize the chance that ineffective therapy
                          is provided (short dose-escalation phase) and
                          utilizes an area under the concentration time
                          curve (AUC) to establish plasma levels of DMP
                          266 and nelfinavir in the pediatric
                          population that are both tolerable and
                          efficacious. [APA 5/26/98: Patients are
                          stratified by age into Cohorts I and II] and
                          receive EFV concurrently with NFV. [APA
                          5/26/98: The initial starting dose of DMP 266
                          for patients in Cohort II is higher than the
                          initial starting dose for patients in Cohort
                          I.] [APA 12/21/98: The initial starting dose
                          for patients in Stratum 1 of Cohort II is
                          higher than the initial starting dose for
                          patients in Cohort I and Stratum 2 of Cohort
                          II.] The initial target AUC for DMP 266 is
                          between 190 and 380 micromoles/h (uM/h). The
                          initial starting dose (based on a 70 kg
                          patient and adjusted for each patient's
                          weight) for the first 6 patients is adjusted
                          on the basis of tolerability and plasma
                          concentrations of DMP 266 after 2 weeks of
                          daily doses. If at least 4 of the first 6
                          patients attain a tolerable dose (dose at
                          which no more than 2 of 6 patients experience
                          Grade 3 or worse toxicity) and target AUC,
                          additional patients may continue to be
                          accrued. However, if any of the initial 6
                          patients experience life-threatening
                          toxicity, further accrual is suspended. [APA
                          5/26/98: An assessment of the tolerability
                          and plasma concentrations of EFV is not
                          required in an initial group of Cohort II
                          patients. Individual dose is based on
                          pharmacokinetic sampling.] Patients receive a
                          given starting dose of DMP 266 and continue
                          on that dose until individual dose
                          adjustments are needed. If a patient's
                          starting dose is tolerated but the target AUC
                          is not achieved, the dose is increased. If
                          the starting dose is well tolerated and
                          target AUC achieved, no adjustment in
                          starting dose is given to future patients. If
                          no tolerated dose achieving at least an AUC
                          of 150 micromoles/h is reached in 4 of 6
                          patients, the study is suspended and
                          alternative dosing regimens, e.g.,
                          twice-daily dosing, are considered. A
                          patient's current dose of DMP 266 is adjusted
                          based on how the dose is tolerated and
                          whether the target AUC is achieved. If a
                          patient does not achieve an AUC of greater
                          than 110 micromoles/h and experiences Grade 3
                          or worse toxicity, the patient is
                          discontinued from the study. [APA 12/21/98:
                          The dose of NFV is the same for patients in
                          Cohort I and Stratum 2 of Cohort II; the dose
                          for patients in Stratum 1 of Cohort II is
                          higher.] The minimum target AUC for NFV is 10
                          mg x h/L. Doses are adjusted for an
                          individual child if AUC falls below threshold
                          at Week 2 or 6. Children with weight no
                          greater than 30 kg receive a lower dose than
                          children with weight greater than 30 kg or
                          Tanner Stage IV. [APA 5/8/00: The first group
                          of 6 patients receives the initial dose of
                          NFV. If none of the 6 patients falls below
                          the target AUC, the remainder of the sample
                          is accrued and treated at this dose. If more
                          than 1 of the 6 patients fall below the
                          target AUC, then another group of 6 patients
                          is accrued and treated at the next higher
                          dose. If exactly 1 of the 6 patients falls
                          below the target AUC, 2 more patients are
                          accrued and treated at the same dose. If 1 of
                          these 2 patients falls below the target AUC,
                          another group of 6 patients is tested on the
                          next higher dose. If neither of these 2
                          patients falls below the target AUC, then the
                          remainder of the sample is accrued and
                          treated at this dose. The dose is escalated
                          until a dose that meets the above criteria is
                          achieved or further dose escalation is
                          prohibited due to toxicity.] The duration of
                          therapy is 48 [APA 12/21/98:104] [APA 5/8/00:
                          208] weeks.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          dosing schedule, Drug efficacy, Drug safety,
                          Drug tolerance, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 105 patients. [AS PER
                          AMENDMENT 5/26/98: Plus 32 in Cohort II ] [AS
                          PER AMENDMENT 5/8/00: Cohort I and Stratum 2
                          of Cohort II closed to further accrual
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks. [AS
                          PER AMENDMENT 12/21/98:104 weeks.] [AS PER
                          AMENDMENT 5/8/00: 208 weeks.].
PROTOCOL DETAILS          ACTUAL ACCRUAL: 90/105 010606.
PROTOCOL DETAILS          STUDY DURATION: 48 weeks. [AS PER AMENDMENT
                          12/21/98:104 weeks.] [AS PER AMENDME
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 26
PROTOCOL DETAILS          VERSION NUMBER & DATE: 5 (000821)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 382
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Confirmed diagnosis of HIV infection
                          as defined by positive culture or PCR on at
                          least 2 occasions or, for patients older than
                          18 months, a positive ELISA and a
                          confirmatory Western blot. 2. Plasma HIV RNA
                          levels above the lower limit of
                          quantification of the Amplicor Assay (greater
                          than 400 copies/ml) at screening. 3. Ability
                          to take oral medication and to comply with
                          protocol requirements. 4. Signed, informed
                          consent from parent or legal guardian.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   OTHER: Plasma HIV RNA levels above the lower
                          limit of quantification of the Amplicor assay
                          (> 400 copies/ml).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study Negative
                          pregnancy test.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Concomitant
                          receipt of 1 or more nucleoside reverse
                          transcriptase inhibitors (NRTIs). Note: These
                          drugs will not be supplied through this
                          protocol. [AS PER AMENDMENT 5/26/98: For
                          Cohort II patients: Patients who are naive to
                          antiretrovirals must initiate therapy with 2
                          NRTIs in addition to the study drugs.
                          Patients who are currently receiving NRTIs
                          must continue them throughout the study.].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 03
                          months less than or equal to 16 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: More
                          than 2 episodes of moderate to severe
                          diarrhea or vomiting lasting more than 4 days
                          within 3 months prior to dosing.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Experimental
                          drugs for any indication within 30 days of
                          initiation of study treatment. 2. NNRTIs or
                          protease inhibitors.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Terfenadine,
                          astemizole, cisapride, clarithromycin,
                          ketoconazole, itraconazole, midazolam,
                          rifabutin, rifampin, triazolam, ergot
                          derivatives, amiodarone, quinidine, or any
                          medications contraindicated for concomitant
                          use with NRTIs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Life
                          expectancy of less than 12 months. 2.
                          Hypersensitivity to any component of the
                          formulation of DMP 266 or NFV. 3. Any
                          toxicity greater than Grade 1 (entry of
                          patients with a Grade 1 clinical laboratory
                          toxicity is permitted at the discretion of
                          the investigator). 4. Acute hepatitis due to
                          any cause. 5. Any clinically significant
                          disease (other than HIV infection) or
                          clinically significant findings during the
                          screening medical history or physical
                          examination that, in the investigator's
                          opinion, would compromise the outcome of this
                          study. 6. A malignancy that requires systemic
                          therapy. 7. An active, AIDS-defining
                          opportunistic infection or disease. (Note:
                          For the purpose of this study, a CD4 count of
                          200 or fewer cells/mm3 in the absence of any
                          other AIDS-defining indicator condition is
                          not considered an AIDS-defining event.).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0269  Efavirenz
RESULTS                   AIDS/20711663. Brundage RC, Fletcher CV,
                          Fiske WD, Kornhauser DM, McNamara J, Mofenson
                          L, Starr SE. Conf Retroviruses Opportunistic
                          Infect. 1999 Jan 31-Feb 4;6th:147 (abstract
                          no. 424).
RESULTS                   AIDS/20711606. Fletcher CV, Brundage RC,
                          Fenton T, Fiske WD, Kornhauser D, McNamara J,
                          Mofenson L, Starr SE. Conf Retroviruses
                          Opportunistic Infect. 1999 Jan 31-Feb
                          4;6th:136 (abstract no. 366).
RESULTS                   MED/20046566. Starr SE, Fletcher CV, Spector
                          SA, Yong FH, Fenton T, Brundage RC, Manion D,
                          Ruiz N, Gersten M, Becker M, McNamara J,
                          Mofenson LM, Purdue L, Siminski S, Graham B,
                          Kornhauser DM, Fiske W, Vincent C, Lischner
                          HW, Dankner WM, Flynn PM. N Engl J Med. 1999
                          Dec 16;341(25):1874-81.
RESULTS                   Fletcher CV, Fenton T, Powell C, Anderson PL,
                          Brundage RC, Spector SA, Starr SE. 8th Conf
                          Retro and Opportun Infect. 2001 Feb 4-8
                          (abstract no. 259).
RESULTS                   Saitoh A, Hsia K, Fenton T, Powell C,
                          Christopherson C, Fletcher CV, Starr SE,
                          Spector SA. 8th Conf Retro and Opportun
                          Infect. 2001 Feb 4-8 (abstract no. 685B).
RESULTS                   MED/20521809. Spector SA, Yong FH, Cabral S,
                          Fenton T, Fletcher CV, McNamara J, Mofenson
                          LM, Starr SE. J Infect Dis 2000
                          Dec;182(6):1769-73.
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks. [AS PER
                          AMENDMENT 12/21/98:104 weeks.] [AS PER
                          AMENDMENT 5/8/00: 208 weeks.].
OTHER TREATMENT INFO.     END POINT: Development of Grade 3 or 4
                          unacceptable toxicity, attributed to the
                          study treatment, achievement of
                          pharmacokinetic targets defined in terms of
                          Area Under the Curve, and the effect of DMP
                          266 and NFV on viral load and CD4 count.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patient has 1 of
                          the following treatment failure criteria: 1)
                          less than 1 log10 drop in plasma HIV RNA
                          level at Week 12, confirmed by a second
                          plasma HIV RNA level obtained within 30 days;
                          2) a plasma HIV RNA level greater than 1000
                          copies/ml on 2 successive determinations in a
                          patient who had previously achieved a plasma
                          HIV RNA level of 400 or fewer copies/ml; or
                          3) a sustained increase in plasma HIV RNA
                          level greater than or equal to 0.75 log10
                          from nadir on 2 consecutive determinations in
                          a patient whose nadir was greater than 400
                          copies/ml. 2. Investigator determines, for
                          any reason, including disease progression,
                          that it is not in the best interest of the
                          patient to continue. 3. Patient entered in
                          violation of the protocol. 4. Use of
                          long-term, unacceptable, concomitant
                          medication. 5. Grade 4 or repeated Grade 3
                          AEs (an intolerable dose). [AS PER AMENDMENT
                          8/21/00: toxicity.] 6. Informed consent is
                          withdrawn. 7. Two consecutive study visits
                          are missed or less than 80% of study
                          medication is consumed over the course of 1
                          month.
OTHER TREATMENT INFO.     MODIFICATION: Doses will be modified or
                          reduced for specific toxicities.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233 No
                          longer recruiting 010116.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Recruiting 000907.
CALIFORNIA                Olive View Med Ctr / Pediatric 14445 Olive
                          View Dr Sylmair, CA 900951752 Recruiting
                          000907.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Recruiting 000907.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 No longer
                          recruiting 001213.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Recruiting 000907.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Recruiting 000907.
LOUISIANA                 Tulane Univ School of Medicine 1430 Tulane
                          Ave New Orleans, LA 70112 Russell Strada
                          [phone] Recruiting 000907.
LOUISIANA                 Earl K Long Early Intervention Clinic 1430
                          Tulane Ave TB-8 New Orleans, LA 70112 Kim
                          Anglin [phone] No longer recruiting
                          000912.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724
                          Recruiting 000907.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Recruiting
                          000907.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Recruiting 010723.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 000907.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Recruiting 000907.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 Recruiting 000907.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714
                          Recruiting 000907.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 010702.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Recruiting 000907.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Recruiting 000907.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Recruiting
                          000907.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Recruiting 000907.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Recruiting 000907.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Recruiting 000907.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Recruiting 000907.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Recruiting 000907.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Recruiting 000907.

4
UNIQUE IDENTIFIER         NIH/00941
PROTOCOL ID NUMBERS       NIAID ACTG 358
PROTOCOL TITLE            A Phase I Trial of the Safety, Tolerance, and
                          Pharmacokinetics of Oral Indinavir
                          Co-Administered with Lamivudine (3TC) and
                          Zidovudine (ZDV) in HIV-1-Infected Pregnant
                          Women During Gestation and Post Partum, and
                          in Their Infants Post Maternal Dosing.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Pregnancy
PROTOCOL CHAIRS           CHAIR  Diana Wara
PROTOCOL CHAIRS           CO-CHAIR  Yvonne Bryson
GENERAL DESCRIPTION       PURPOSE: To assess the pharmacokinetics,
                          safety, tolerance, and efficacy of indinavir
                          when given in combination with lamivudine
                          (3TC) and zidovudine (ZDV) to HIV-1-infected
                          pregnant women. To assess the
                          pharmacokinetics of indinavir in cord and
                          neonatal samples following maternal dosing
                          and the safety and tolerance of prior
                          maternal dosing in the newborn. To assess the
                          antiviral effect and durability of the
                          combination of indinavir, 3TC, and ZDV in
                          reducing maternal plasma HIV RNA levels.
GENERAL DESCRIPTION       RATIONALE: Despite the dramatic reduction of
                          perinatal HIV transmission following the
                          administration of ZDV to mothers and infants,
                          new, more effective strategies are needed. An
                          increasing number of women may require
                          combination antiretroviral therapy for their
                          own disease because they may be resistant to
                          ZDV, may have high viral loads, or may have
                          previously transmitted HIV to an infant while
                          on ZDV monotherapy. The initiation of triple
                          combination therapy, including a protease
                          inhibitor indinavir, during gestation may be
                          the most effective in reducing maternal virus
                          load prior to delivery, thereby potentially
                          benefitting both mother and child.
GENERAL DESCRIPTION       METHODOLOGY: Women: Antepartum (until active
                          labor): Indinavir plus 3TC plus ZDV.
                          Intrapartum (active labor until cord
                          clamping): 3TC plus ZDV. Postpartum (after
                          cord clamped to 12 weeks): Indinavir plus 3TC
                          plus ZDV. Infants: 3TC plus ZDV as soon as
                          oral intake is tolerated (preferably within
                          12 hours of birth) and continuing for 6
                          weeks. [AS PER AMENDMENT 1/27/99: For
                          maternal dosing, one Combivir tablet bid can
                          be substituted for the individual formulation
                          of 3TC and ZDV. For mothers who receive
                          Combivir during the antepartum period,
                          Combivir is held during labor and delivery,
                          and the separate formulations of ZDV and 3TC
                          are used. Patiens who prematurely discontinue
                          study treatment should continue to be
                          followed on study for the duration of the
                          study.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy,
                          Combination pharmacokinetics, Drug efficacy,
                          Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients. (At least 10
                          mother/infant pairs).
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Women: 24-38
                          weeks (12-26 weeks antepartum, 12 weeks
                          postpartum). Infants: 24 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 28/24 010508.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 14
PROTOCOL DETAILS          VERSION NUMBER & DATE: (990809)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 358
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection documented by ELISA
                          and confirmed by a Western blot or other
                          appropriate confirmatory test. 2. Confirmed
                          gestational age of 14 to 28 weeks based upon
                          menstrual history and confirmed by an early
                          ultrasound or by serial sonographic
                          determinations. NOTE: Gestational age given
                          by the date of the last menstrual period and
                          that given by the last ultrasound must be
                          within 14 days of each other. 3. Normal Level
                          II targeted ultrasound at screening. 4.
                          Willingness and ability to maintain vigorous
                          daily hydration (6 8-ounce glasses of water)
                          throughout the study. 5. Signed, informed
                          consent from parent or legal guardian for
                          patients less than age 18.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5.
PATIENT INCLUSION CRIT.   OTHER: ANC >= 1,000 cells/mm3. Amylase <= 1.5
                          X ULN with normal lipase.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Women in the first or
                          second trimester of pregnancy.
PATIENT INCLUSION CRIT.   WEIGHT: Required: Infants: 2 kg or more.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: ddI, ddC, d4T, or
                          ZDV. [AS PER AMENDMENT 1/27/99: Prior
                          treatment with non-nucleoside reverse
                          transcriptase inhibitors is allowed, as is
                          less than 3 weeks of prior therapy with 3TC.
                          Women currently receiving 3TC in combination
                          with any of the drugs listed above and who
                          have received 3TC for more than 3 weeks are
                          eligible only if, over the past 3 months,
                          they have had a stable or increasing CD4
                          count and their HIV RNA level has been less
                          than 400 copies/ml (Roche).] [AS PER
                          AMENDMENT 8/9/99: Less than 3 weeks of
                          indinavir in combination with ZDV and 3TC is
                          allowed. Women currently on indinavir, 3TC,
                          and ZDV for longer than 3 weeks are eligible
                          only if, in the 3 mont
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of chronic liver or renal disease
                          including kidney stones or Gilbert's
                          syndrome.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current substance or
                          alcohol abuse [AS PER AMENDMENT 1/27/99:
                          Methadone is allowed].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior protease
                          inhibitor therapy. [AS PER AMENDMENT 8/9/99:
                          Less than 3 weeks of indinavir in combination
                          with ZDV and 3TC is allowed. Women currently
                          on indinavir, 3TC, and ZDV for longer than 3
                          weeks are eligible only if, in the 3 months
                          prior to enrollment, CD4 counts are stable or
                          increasing and HIV RNA PCR is less than 400
                          copies/ml. Women switching from 1 protease
                          inhibitor to indinavir are also eligible as
                          long as it is within the 3-week time frame.]
                          2. 3TC prior to pregnancy or for more than 3
                          weeks during this pregnancy [AS PER AMENDMENT
                          01/27/99: See exceptions noted above]. 3.
                          Non-nucleoside reverse transcriptase
                          inhibitors within 3 weeks prior to study
                          entry. Excluded (within 1 week of protocol
                          therapy): 4. Astemizole, cisapride,
                          clarithromycin, erythromycin, itraconazole,
                          ketoconazole, miconazole, midazolam,
                          terfenadine, and triazolam. Excluded (within
                          4 weeks of protocol therapy): 5.
                          Barbiturates, carbamazepine, dexamethasone,
                          phenytoin, rif
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded:
                          Barbiturates, astemizole, carbamazepine,
                          clarithromycin, cisapride, dexamethasone,
                          erythromycin, itraconazole, ketoconazole,
                          midazolam, miconazole, terfenadine,
                          phenytoin, rifabutin, rifampin, and
                          triazolam.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions or symptoms are excluded: Women:
                          1. Intolerance to ZDV or 3TC. 2. Active
                          opportunistic infection and/or serious
                          bacterial infection at the time of study
                          entry. 3. Chronic malabsorption or chronic
                          diarrhea. 4. Medical complications whose
                          treatment would include the use of disallowed
                          medications, including epilepsy and
                          malignancy. 5. Multiple fetal pregnancy
                          (twins or more births). 6. Intrauterine
                          growth restriction below the third percentile
                          for gestational age (by ultrasound) [AS PER
                          AMENDMENT 01/27/99: below the 10th percentile
                          for gestational age]. 7. Abnormal amniotic
                          fluid volume on entry. 8. Enrollment in other
                          therapeutic/vaccine clinical trials. Infants:
                          9. Major fetal anomaly by pre-entry
                          ultrasound, hydrops or abruptio placenta that
                          is incompatible with life or that would
                          interfere with the conduct of the study. 10.
                          Unable to tolerate oral medications for more
                          than 72 hours (infant will receive IV ZDV if
                          NPO more than 12 hours until
                          discontinuation). 11. Severe anemia,
                          hypovolemia, or hyperbilirubinemia requiring
                          volume replacement and/or blood products. 12.
                          Documented or suspected serious infection,
                          cardiac, respiratory, or metabolic illness,
                          or other immediate life-threatening
                          conditions. [AS PER AMENDMENT 1/27/99: The
                          following additional criteria are added to
                          exclude women with risk factors for premature
                          birth or poor infant outcomes: 11. Poor
                          obstetrical history, including: spontaneous
                          abortions (3 or more), prior preterm or
                          low-birth-weight infant (less than 2,500 g),
                          major congenital anomalies, unexplained
                          stillbirth, or unexplained neonatal loss. 12.
                          Obstetrical complications in this pregnancy,
                          including: presence of major congenital
                          anomalies, multiple gestation, placenta
                          previa or abruption, pre-eclampsia,
                          eclampsia, preterm premature rupture of
                          membrane resulting in tocolysis. 13. Medical
                          complications or conditions, including:
                          gestational diabetes prior to enrollment,
                          pre-gestational diabetes
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0233  Indinavir sulfate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Women: Antepartum
                          and postpartum: 200 mg tid. Intrapartum: 2
                          mg/kg over 1h, then 1 mg/kg/h. Infants: 2.6
                          mg/kg tid (or 2 mg/kg IV q 8h). Drug 2:
                          Women: 150 mg bid. Infants: 2 mg/kg bid. Drug
                          3: Women: Antepartum and postpartum: 800 mg q
                          8h
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Women: Antepartum and
                          postpartum: 600 mg. Infants: 7.8 mg/kg (or 6
                          mg/kg IV). Drug 2: Women: 300 mg. Infants: 4
                          mg/kg. Drug 3: Women: Antepartum and
                          postpartum: 2400 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Women: 24-38 weeks (12-26
                          weeks antepartum, 12 weeks postpartum).
                          Infants: 6 weeks.
OTHER TREATMENT INFO.     END POINT: Pharmacokinetics, safety,
                          toxicity, and efficacy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patient or legal
                          guardian refuses further treatment and/or
                          follow-up evaluations. 2. Further
                          participation would be detrimental to the
                          patient's health or well-being. 3.
                          Unacceptable toxicity. Women: 4. Failure to
                          comply with the study requirements so as to
                          cause harm to self or seriously interfere
                          with the validity of the study results.
                          Infants: 5. Mother is discontinued prior to
                          birth.
OTHER TREATMENT INFO.     MODIFICATION: Doses will be modified or
                          reduced for specific toxicities.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 980420.
CALIFORNIA                San Francisco Gen Hosp 1001 Potrero Ave /
                          Ward 6 / D-4 San Francisco, CA 94110 Kelly
                          Slaven [phone] Recruiting 980420.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 970918.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          000509.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] No longer
                          recruiting 000127.
MASSACHUSETTS             Brigham and Women's Hosp 75 Francis St /
                          Children's Hosp AIDS Program Boston, MA 02115
                          Arlene Buck [phone] Recruiting 980408.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 980527.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          990915.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 990915.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] No longer recruiting 991006.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone] No longer
                          recruiting 010410.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 980408.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] No longer
                          recruiting 980730.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 980204.

5
UNIQUE IDENTIFIER         NIH/00932
PROTOCOL ID NUMBERS       NIAID ACTG 247
PROTOCOL TITLE            A Randomized, Double-Blind, Controlled Study
                          of an Increased Caloric Density Infant
                          Formula and Its Effect on Growth and
                          Nutritional Status in HIV-Infected Infants.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
PROTOCOL CHAIRS           CHAIR  Harland S Winter
PROTOCOL CHAIRS           CO-CHAIR  James Oleske
GENERAL DESCRIPTION       PURPOSE: To determine whether caloric
                          supplementation with 25.7 kcal/oz study
                          formula as compared with standard study
                          formula (20 kcal/oz), started within the
                          first 14 days of life in HIV-infected
                          infants, results in improved growth as
                          measured by weight and length at 28 weeks. To
                          determine the effect of nutritional
                          supplementation on head circumference as an
                          indicator of cerebral growth at 28 weeks. To
                          evaluate both short-term (8 weeks) and
                          long-term (28 weeks) tolerability of a
                          concentrated formula as compared to standard
                          formula in HIV-exposed infants. To determine
                          the effect of nutritional supplementation on
                          immunologic status as measured by CD3+CD4+
                          and CD3+CD8+ lymphocyte count, the occurrence
                          of opportunistic infections, and on
                          parent/guardian reported quality of life.
GENERAL DESCRIPTION       RATIONALE: In order to meet the optimal
                          nutritional needs of HIV-infected infants, it
                          is critical that nutritional intervention
                          begin early. Early nutritional intervention
                          may help reduce the susceptibility to or
                          severity of primary HIV and/or opportunistic
                          infections and add to the quality of life for
                          children perinatally infected with HIV.
GENERAL DESCRIPTION       METHODOLOGY: In this double-blind, controlled
                          study perinatally HIV-exposed infants less
                          than 15 days old at time of study entry are
                          randomized to one of two arms to receive
                          either concentrated formula or standard
                          formula for 8 weeks after being stratified by
                          gestational age: less than 37 versus greater
                          than 37 completed weeks. At the 8-week visit
                          using a previously determined 8:1 random
                          allocation, 89% of singleton infants with
                          negative HIV-specific tests are discontinued
                          from study treatment and further follow-up.
                          The other 11% of these singleton infants with
                          negative HIV-specific tests continue study
                          treatment with open-label standard formula
                          until Week 28 (control group). Singleton
                          infants with positive HIV-specific tests
                          continue on the blinded portion of study and
                          receive formula as initially assigned until
                          Week 28. For a given multiple birth, if any
                          of the infants at the 8-week study visit are
                          determined to be infected, all the infants
                          from that birth continue their initial
                          blinded treatment assignment until Week 28;
                          if none of the infants are determined to be
                          infected at this time, all the infants from
                          that birth continue study treatment with
                          open-label standard formula until Week 28.
                          All infants assigned to receive study
                          treatment through Week 28 continue study
                          follow-up until 12 months of age.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 2000 patients. 1900 x 56
                          days; 380 x 12 months.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 28 weeks
                          of treatment and 12 months of follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1661/2000 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 72
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (970402)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 247
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Parallel Designs;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Infants must
                          have: 1. HIV-infected mothers, as proven by
                          two positive tests for HIV antibody performed
                          with a federally licensed antibody test, each
                          including a repeated positive ELISA test and
                          a confirmatory Western blot. Note: An effort
                          will be made to enroll mothers prior to
                          randomization of infants at delivery. 2.
                          Exact birth-weight documentation. 3. A
                          caregiver willing to comply with study
                          requirements, i.e., keep dietary intake
                          records. 4. A life expectancy greater than 28
                          weeks. Note: Multiple births are eligible
                          provided study criteria are met.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding.
PATIENT INCLUSION CRIT.   WEIGHT: Greater than or equal to 1.8 kg.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: Nonstudy formula
                          for first 14 days after birth.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 01 days
                          less than or equal to 14 days.s.

PATIENT EXCLUSION CRIT.   WEIGHT: Less than 1.8 kg.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Agents that
                          alter growth, e.g., Megace, corticosteroids,
                          IGF-1, or growth hormone.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Evidence of congenital anomalies or
                          conditions that may result in infant
                          mortality within 28 weeks (e.g., anencephaly,
                          renal agenesis, pulmonary hypoplasia, etc.)
                          and/or unable to sustain growth by commencing
                          oral feedings by 14 days of age
                          (gastroschisis, omphalocele, esophageal
                          atresia, diaphragmatic hernia, etc.). 2.
                          Metabolic disorder or transport defect
                          resulting in malabsorption.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0274  Infant Formula
RESULTS                   ICA12/98404342. Kaiser M, Hagopian J,
                          Ernestine J, Moye J, Fowler M, Nesel C. Int
                          Conf AIDS. 1998;12:845-6 (abstract no.
                          42358).
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Infants are fed the
                          assigned study formulas; standard, kcal/oz or
                          concentrated, 25.7 kcal/oz, as needed, for 28
                          weeks
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 20 or 25.7
                          kcal/fluid oz formula
OTHER TREATMENT INFO.     TREATMENT DURATION: All HIV-infected and 11%
                          of exposed, uninfected children are treated
                          for 28 weeks.
OTHER TREATMENT INFO.     END POINT: Weight, length, weight for length,
                          head circumference, and body composition at
                          28 weeks; tolerability; immunologic status;
                          occurrence of opportunistic infections; and
                          quality of life.
OTHER TREATMENT INFO.     DISCONTINUE: Treatment is discontinued for
                          the following: 1. Infant unable to receive
                          nutrition by mouth for greater than 7 days.
                          2. Infant fails to grow. 3. Investigator
                          decides continuing in study would be harmful
                          to the child. 4. Child needs a treatment not
                          allowed while on study. 5. Unable to keep
                          appointments or take study drugs as
                          instructed. 6. Intolerance to 25.7 kcal/oz
                          study formula. 7. Study is cancelled by
                          sponsoring agency.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          970924.
ALABAMA                   Univ of South Alabama 1504 Springhill Avenue
                          Mobile, AL 36604 Julie Bebawy [phone]
                          Recruiting 970919.
ARIZONA                   Phoenix Childrens Hosp 909 East Brill Street
                          Phoenix, AZ 85006 Judith O'Haver
                          [phone] Recruiting 970919.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 970919.
CALIFORNIA                Cedars Sinai / UCLA Med Ctr 8700 Beverly
                          Boulevard Los Angeles, CA 900481804 Zane
                          O'Keefe [phone] Recruiting 991102.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 970919.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 970919.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] Recruiting 970919.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] Recruiting 970919.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 971121.
CONNECTICUT               Connecticut Children's Med Ctr 263 Farmington
                          Ave Farmington, CT 060303805 Gail Karas
                          [phone] No longer recruiting 010123.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] Recruiting 970919.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 970919.
FLORIDA                   Sacred Heart Children's Hosp / CMS of Florida
                          5192 Bayou Blvd Pensacola, FL 32503 Susan
                          Wilson [phone] Recruiting 001024.
FLORIDA                   Arnold Palmer Hosp for Children & Women 92
                          West Miller St Orlando, FL 32806 Kerry Mullen
                          [phone] Recruiting 970919.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Brenda Haliburton-Jones [phone]
                          Recruiting 980108.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 971106.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 970919.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 970919.
FLORIDA                   Univ of South Florida One Davis Med Building
                          / Suite 502 Tampa, FL 33606 Jennifer Lane
                          [phone] Recruiting 970919.
FLORIDA                   Univ of Miami / Jackson Memorial Hosp 1500
                          Northwest 12th Ave / 8th Floor Miami, FL
                          33136 Patricia Bryan [phone] Recruiting
                          980108.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          970919.
GEORGIA                   The Med Ctr Inc 710 Center St Columbus, GA
                          31901 Dawn Barnes [phone] Recruiting
                          990915.
GEORGIA                   Med College of Georgia 1120 15th St / Dept of
                          Pediatrics / HF 1135 Augusta, GA 30912 Teresa
                          Horne [phone] Recruiting 970919.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 970919.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 990119.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] Recruiting
                          970919.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 970919.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 971008.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 971003.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Sue Lovelace [phone]
                          Recruiting 971003.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 970919.
MISSOURI                  Washington Univ School of Medicine One
                          Childrens Place St Louis, MO 63110 Phyllis
                          Ballard [phone] Recruiting 980217.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 970919.
NORTH CAROLINA            Univ of North Carolina at Chapel Hill / Duke
                          Univ Med Ctr PO Box 3499 Durham, NC 27710
                          John Swetnam [phone] Recruiting 991227.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 970919.
NEW JERSEY                St Peter's Med Ctr 254 Easton Ave New
                          Brunswick, NJ 08903 Marian Lake [phone]
                          Recruiting 000824.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 981203.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Silvia Callejas
                          [phone] Recruiting 980116.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 970919.
NEW JERSEY                Cooper Hosp - Univ Med Ctr / UMDNJ - New
                          Jersey Med Schl One Cooper Plaza Camden, NJ
                          08103 Mary Jo Hoyt [phone] Recruiting
                          000621.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 970919.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Denise Swindell
                          [phone] Recruiting 980624.
NEW YORK                  Cornell Univ Med College 1300 York Ave / PO
                          Box 296 New York, NY 10021 Kathleen O'Keefe
                          [phone] Recruiting 970919.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 971014.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 970919.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 971003.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          970919.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 970919.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 980504.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 971124.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 971021.
OHIO                      Columbus Children's Hosp 700 Children's Dr
                          Columbus, OH 432052696 Jane Hunkler
                          [phone] Recruiting 980403.
OTHER                     Federal University of Minas Dept.
OTHER                     Hosp Univ Clementino Fraga Filho Lab de AIDS
                          / Av BrigadeiroTrompowski s/n / 4o andar Ilha
                          do FuRio de Janeiro RJ, Susie Nogueira
                          (552)159-05252 Recruiting 010411.
OTHER                     Princess Margaret Hosp Shirley St / PO Box
                          N1784 Nassau, Marva Jervis [phone]
                          Recruiting 010318.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          970923.
OTHER                     Ponce Univ Hosp Immunology Clinic / Area
                          Vieja / Carretera #14 Bo Machuelo Ponce, PR
                          00731 Betsy Ruiz [phone] Recruiting
                          970919.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 970919.
OTHER                     Mayguez Med Ctr / Regional Immunology Clinic
                          410 Hostos Ave Mayguez, PR 00680 Carmen
                          Montalvo [phone] Recruiting 980925.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 970919.
OTHER                     Caguas Regional Hosp PO Box 5729 Caguas, PR
                          00726 Wanda Rivera [phone] No longer
                          recruiting 001121.
SOUTH CAROLINA            Univ of South Carolina School of Med 4
                          Richland Med Park / Suite 203 Columbia, SC
                          29203 Alisa Lucas [phone] Recruiting
                          970919.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone] No
                          longer recruiting 010222.
TEXAS                     Univ of Texas Health Sciences Ctr 7703 Floyd
                          Curl Dr San Antonio, TX 78284 Rachel Davis
                          [phone] Recruiting 970919.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 971009.
TEXAS                     Children's Med Ctr of Dallas 1935 Motor St
                          Dallas, TX 75235 Diane Ramirez [phone]
                          Recruiting 980923.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 970919.
WASHINGTON                Hosp dos Servidores do Estado Servico de D
                          Infecciosas (DIP HSE) / Anexo IV 5 / Rua
                          Sacadura Cabral 178 Rio de Janeiro,
                          Jacqueline Menezes (552)151-81594 Recruiting
                          001019.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 990615.

6
UNIQUE IDENTIFIER         NIH/00905
PROTOCOL ID NUMBERS       NIAID ACTG 326
PROTOCOL TITLE            A Phase I/II Study to Evaluate the Safety and
                          Immunogenicity of ALVAC HIV Vaccines Alone
                          and with AIDSVAX B/B in Children Born to
                          HIV-Infected Mothers.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Preventative HIV Vaccine
TRIAL CATEGORY            Therapeutic AIDS Vaccine
PROTOCOL CHAIRS           CHAIR  John Lambert
PROTOCOL CHAIRS           CO-CHAIR  Daniel Johnson
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          immunogenicity of live recombinant Canarypox
                          HIV ALVAC vaccine alone or in combination
                          with a subunit vaccine in infants who are of
                          indeterminate status born to HIV-infected
                          women. [AS PER AMENDMENT 11/5/97: To
                          determine the safety and immunogenicity of
                          live recombinant Canarypox HIV ALVAC vaccine
                          (vCP205) in infants who are of indeterminate
                          status born to HIV-infected women.] [AS PER
                          AMENDMENT 9/9/99: To determine the safety and
                          immunogenicity of live recombinant Canarypox
                          ALVAC HIV vaccines (vCP205 and vCP1452) alone
                          and in combination with AIDSVAX B/E gp120 in
                          infants who are of indeterminate status born
                          to HIV-infected women. To evaluate humoral
                          and cell-mediated responses, including
                          cytotoxic T cell and lymphoproliferative
                          responses to HIV-specific antigens and
                          non-HIV antigens in immunized infants.] [AS
                          PER AMENDMENT 1/24/00: AIDSVAX B/E has been
                          replaced with AIDSVAX B/B.]
GENERAL DESCRIPTION       RATIONALE: Transmission of HIV from an
                          untreated infected mother to her offspring is
                          thought to occur to some infants perinatally
                          and others at parturition. It is possible
                          that administration of an immunogenic vaccine
                          can reduce the vertical transmission of HIV-1
                          or moderate its course in infected infants.
                          Successful early sensitization to HIV
                          epitopes might succeed in preventing HIV
                          infection. Alternately, the enhancement of
                          HIV-specific immune function might also
                          succeed in modifying HIV replication and
                          affecting disease progression.
GENERAL DESCRIPTION       METHODOLOGY: Sixty infants are treated in
                          this randomized, double-blind study; 45
                          infants receive recombinant Canarypox virus,
                          ALVAC-HIV vCP205, and 15 receive placebo.
                          Mothers serve as proxy for their infants. All
                          infants receive a minimum of four
                          immunizations, at Weeks 0 (within 72 hours of
                          birth), 4, 8, and 12. Initially, 24 patients
                          are randomized to receive one of two doses of
                          vCP205 or a saline placebo. When a suitable
                          subunit vaccine is available, the protocol
                          will be amended and 36 additional infants
                          will be randomized to receive vCP205 alone or
                          with a subunit vaccine at Weeks 4 and 8 (or
                          vaccine placebo with or without subunit
                          placebo). [AS PER AMENDMENT 11/5/97: 18
                          infants receive ALVAC-HIV vCP205 at one of
                          two doses and 6 receive placebo.] [AS PER
                          AMENDMENT 9/9/99: Cohort 1 received vCP205.
                          Cohort 2 received a higher dose of vCP205.
                          Cohort A received vCP205 placebo (saline).
                          Cohorts 1, 2, and A were double-blinded and
                          closed to accrual in March 1999. As of
                          September 1999, infants are randomized to one
                          of four new cohorts. Cohort 3 receives
                          vCP1452 at Weeks 0, 4, 8, and 12. Cohort 4
                          receives vCP1452 at Weeks 0 and 4, then
                          receives vCP1452 plus AIDSVAX B/E gp120 at
                          Weeks 8 and 12. Cohort B receives vCP1452
                          placebo at Weeks 0, 4, 8, and 12. Cohort C
                          receives vCP1452 placebo at Weeks 0 and 4,
                          then receives vCP1452 placebo plus AIDSVAX
                          B/E placebo at Weeks 8 and 12. All infants
                          are followed every 2 weeks for the first 14
                          weeks of life, and then every 6 months until
                          age 2. Cord blood is used to establish
                          autologous B cell lines, and CTL assays are
                          performed to characterize the immune response
                          to HIV. In addition, CD4 count, viral load,
                          and mucosal antibody responses are measured.
                          Immunized infants who are not infected with
                          HIV serve as controls for the immunogenicity
                          of the vaccines in the infected infants.] [AS
                          PER AMENDMENT 1/24/00: AIDSVAX B/E has been
                          replaced with AIDSVAX B/B.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Immunology, Vaccine prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 48 patients. 45 in the
                          vaccine cohort; 15 in the placebo cohort. [AS
                          PER AMENDMENT 11/5/97: 18 in the vaccine
                          cohort and 6 in the placebo cohort.] [AS
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 104 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 91/48 010717.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 27
PROTOCOL DETAILS          VERSION NUMBER & DATE: 4 (000124)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 326
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Women must have:
                          1. HIV infection. 2. Ability to provide
                          written informed consent and willingness to
                          comply with study requirements. Infants must
                          have: 1. Been born to HIV-infected women at
                          37 weeks gestational age or later. 2. Written
                          informed consent of a parent or legal
                          guardian.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 12 g/dl Infants.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 100000 /mm3 Infants.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified for infants
                          or women.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN ULN (Upper Limit of
                          Normal). Infants.
PATIENT INCLUSION CRIT.   CREATININE: < 1.3 Infants.
PATIENT INCLUSION CRIT.   OTHER: Infants: BUN <= 20 mg/dl.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed for women:
                          Antiretroviral therapy. Antiretroviral
                          therapy must be offered to all women
                          participating in the study. Allowed for
                          infants: 1. Antiretroviral therapy in a
                          regimen similar to ACTG 076. 2. Immunizations
                          according to current standards. Routine
                          immunizations should be 2 weeks before or 2
                          weeks after the study vaccine. Study vaccine
                          can be given 36 hours or more after a
                          hepatitis B vaccine received in the first 24
                          hours of life.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 00 days
                          less than or equal to 03 days.s.

PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded for women: 1.
                          Investigational agents during pregnancy. 2.
                          Passive or active immunotherapy during
                          pregnancy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded for infants:
                          1. Passive or active HIV-specific
                          immunotherapy other than the study candidate
                          vaccines. 2. Investigational agents. 3.
                          Immune modulators and IVIG until 30 days
                          after the Week 12 vaccine dose.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Women with the following
                          conditions or symptoms are excluded:
                          Seropositivity for hepatitis B antigen.
                          Infants with the following conditions or
                          symptoms are excluded: 1. Serious bacterial
                          infection, metabolic illness, or other
                          immediate life-threatening conditions. 2.
                          Breast-feeding.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0230  ALVAC-HIV MN120TMG (vCP205)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0295  MN rgp120/HIV-1 and GNE8
                          rgp120/HIV-1
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Cohort 1: vCP205
                          (10^5.8) at Weeks 0, 4, 8, and 12. Cohort 2:
                          vCP205 (10^6.3) at Weeks 0, 4, 8, and 12.
                          Drug 2: [AS PER AMENDMENT 1/24/00: Cohort 4:
                          0.33 ml (300 microat Weeks 8 and 12.] Drug 3:
                          [AS PER AMENDMENT 9/9/99: Cohort 3: 1 ml at
                          Weeks 0, 4,and 12. Cohort 4: 1 ml at Weeks 0,
                          4, 8, and 12.]
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular
                          injection. Drug 2: Intramuscular injection.
                          Drug 3: Intramuscular injection
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 weeks.
OTHER TREATMENT INFO.     END POINT: The development of Grade 3 or 4
                          adverse events that are attributed to the
                          study treatment; immunologic decline as
                          evidenced by a CD4 percentage of less than
                          20%.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Unacceptable
                          toxicity. 2. Progression of HIV disease
                          status, as indicated by development of an
                          AIDS-defining opportunistic infection,
                          development of wasting disease or failure to
                          thrive, development of HIV-associated
                          malignancy, or 2 or more episodes of
                          bacterial septicemia and/or meningitis. 3.
                          Immunological decline, defined as less than
                          20% CD4, regardless of HIV infection status.
                          4. Noncompliance with study requirements. 5.
                          By request of the Food and Drug
                          Administration, pharmaceutical companies, IND
                          sponsor (DAIDS), or parent or legal guardian.
OTHER TREATMENT INFO.     MODIFICATION: Doses will be modified or
                          reduced for specific toxicities. Vaccination
                          may be delayed for active intercurrent
                          infection, fever above 101 F, disease of the
                          immune system, tuberculosis,
                          immunosuppressive therapy, or receipt of any
                          other vaccine, as per protocol guidelines.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 000817.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 000817.
CALIFORNIA                San Francisco Gen Hosp 1001 Potrero Ave /
                          Ward 6 / D-4 San Francisco, CA 94110 Kelly
                          Slaven [phone] Recruiting 000817.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 000817.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] No longer recruiting
                          010130.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] No longer recruiting 010115.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 000817.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 001013.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          000817.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 000817.
ILLINOIS                  Mt Sinai Hosp Med Ctr / Dept of Pediatrics
                          Women's and Children's HIV Program / 15th
                          Street and CaliforniaChicago, IL 60608 Brenda
                          Wolfe [phone] Recruiting 000824.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          000817.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 000817.
LOUISIANA                 Univ Hosp 2021 Perdido St New Orleans, LA
                          70112 Kim Anglin [phone] Recruiting
                          000817.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000817.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 000817.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 000817.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 000817.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Sue Lovelace [phone]
                          Recruiting 000817.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 000817.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010424.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 000817.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 000817.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 000817.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          000817.
PENNSYLVANIA              Hosp of the Univ of Pennsylvania 3400 Spruce
                          St / Maloney Building / 2nd Floor
                          Philadelphia, PA 19104 Kathy Mooney
                          [phone] Recruiting 000817.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 000817.

7
UNIQUE IDENTIFIER         NIH/00897
PROTOCOL ID NUMBERS       NIAID ACTG 351
PROTOCOL TITLE            Phase I/II Trial of CD4-IgG2 in HIV-Infected
                          Children.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  William Shearer
PROTOCOL CHAIRS           CO-CHAIR  Stuart Starr
GENERAL DESCRIPTION       PURPOSE: Part 1: To determine the safety,
                          toxicity, and pharmacokinetics of single-dose
                          CD4-IgG2 in HIV-infected children. To
                          determine the anti-HIV effects of single-dose
                          CD4-IgG2 in HIV-infected children. Part 2: To
                          determine the safety, toxicity, and
                          pharmacokinetics of multiple doses of
                          CD4-IgG2 in HIV-infected children. To
                          determine the anti-HIV effects of multiple
                          doses of CD4-IgG2 in HIV-infected children.
GENERAL DESCRIPTION       RATIONALE: Since CD4 is the high-affinity
                          receptor for HIV-1, molecules such as
                          CD4-IgG2, which incorporate the gp120 binding
                          region of CD4, have the potential to bind and
                          neutralize all strains of the virus. [AS PER
                          AMENDMENT 4/25/00: Study results have
                          demonstrated that the product is safe in
                          children, well tolerated, and may have
                          antiviral properties. With these encouraging
                          results in hand, an extra cohort has been
                          added using twice the dose of rCD4-IgG2 as in
                          Cohort I.]
GENERAL DESCRIPTION       METHODOLOGY: The study is conducted in two
                          parts. In Part 1 patients receive a single
                          dose of CD4-IgG2 intravenously at 1 of 4 dose
                          levels. A minimum of 3 patients are treated
                          at a given dose level. If none of these 3
                          patients experience Grade 3 or 4 toxicity,
                          patients are escalated to the next dose
                          level. If any of these 3 patients have
                          life-threatening toxicities or if more than 1
                          of these 3 patients experience
                          non-life-threatening Grade 3 or 4 toxicities,
                          escalation stops and the prior dose (if any)
                          is considered the maximum tolerated dose
                          (MTD). If 1 of these 3 patients experiences
                          non-life-threatening Grade 3 or 4 toxicities,
                          3 additional patients are treated at this
                          dose level. If 1 or more of these 3
                          additional patients has Grade 3 or 4
                          toxicity, escalation stops. If none of these
                          3 additional patients has Grade 3 or 4
                          toxicity, patients are escalated to the next
                          dose level. Part 2 provides additional data
                          on the safety, toxicity and pharmacokinetics
                          of CD4-IgG2 when given in multiple doses.
                          Patients receive the highest safe dose (MTD)
                          as established in Part 1. Treatment is given
                          intravenously once weekly at Weeks 0, 1, 2,
                          and 3. If insufficient activity is seen at
                          this dose level, 6 additional patients will
                          be enrolled at a higher dose level. Patients
                          who participate in Part 1 may enroll in Part
                          2 provided they are followed for at least 3
                          months and meet inclusion criteria for Part
                          2. If any patient experiences a
                          life-threatening condition due to CD4-IgG2,
                          the study will stop. [AS PER AMENDMENT
                          4/25/00: Cohort II receives twice the dose of
                          Cohort I intravenously once weekly at Weeks
                          0, 1, 2 and 3. Pharmacokinetic samples are
                          obtained at pre-dose and 1 hour after the
                          doses are administered at Weeks 0, 1, and 2;
                          and pre-dose, 1 hour, 24 hours, and Days 3,
                          7, and 14 after the dose are administered at
                          Week 3. An overnight stay in the hospital is
                          recommended for the first 24 hours. At Weeks
                          0, 1, 2, and 3, virology testing including
                          HIV-1 RNA is performed with each infusion of
                          CD4-IgG. Follow-up monitoring of patients is
                          done once a month for 4 months for patients
                          in Cohort II.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug dosing schedule, Drug
                          efficacy, Drug safety, Maximum tolerated dose
                          (MTD), Pharmacokinetics, Drug toxicity.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients. Part 1:
                          Minimum of 12 (at least 3 per dose level);
                          maximum of 24. Part 2: Minimum of 6 or 12 (if
                          a higher dose is considered); maximum of
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Part 1:
                          Single-dose administration with 14-day
                          follow-up per dose level. After highest safe
                          dose level (MTD) is achieved, follow-up
                          monitoring will be done once a month for 4
                          months. Part 2: Doses will be administered
                          once weekly at Weeks 0, 1,
PROTOCOL DETAILS          ACTUAL ACCRUAL: 21/24 010703.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 9
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (000425)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 351
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Previously documented HIV infection
                          as defined by positive ELISA and a
                          confirmatory Western blot. 2. Evidence of CDC
                          Category 3 immunologic suppression: For ages
                          2-5, a CD4 cell count less than 500
                          cells/mm3. For ages 6-12, a CD4 cell count
                          less than 200 cells/mm3. [AS PER AMENDMENT
                          12/31/97: CD4 requirements were deleted.] 3.
                          Evidence of CDC Category N, A, or B clinical
                          disease. [AS PER AMENDMENT 12/31/97: The CDC
                          clinical disease criterion was deleted.] 4.
                          Signed, informed consent from parent or legal
                          guardian for patients under age 18. Patients
                          in Part 2 must have: Detectable and stable
                          RNA HIV of 10,000 copies per/ml or more (2
                          values 30 days apart).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 500 cells/mm3 (2-5
                          year olds) ( 0 - 100 - 200 - 300 - 400 - 499
                          ), < 200 (6-12 year olds) ( 0 - 100 - 199 ).
                          [AS PER AMENDMENT 12/31/97: CD4 requirements
                          deleted.].
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN ULN (Upper Limit of age
                          adjusted Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.2 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant Pubertal
                          females should be screened for pregnancy.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable unchanged
                          antiretroviral therapy for three months prior
                          to entry.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 02
                          years less than or equal to 12 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [AS PER AMENDMENT
                          4/25/00: Patients with the following prior
                          conditions are excluded from Part 2 - Cohort
                          II: Previous enrollment in Part 2 - Cohort I.
                          (Previous enrollment in Part 1 is allowed.)].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Routine pediatric
                          vaccinations within 30 days prior to entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Steroids
                          or other immunosuppressive therapy. 2.
                          Prophylactic administration of intravenous
                          immunoglobulin (IVIG). 3. Current
                          participation in a vaccine trial.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Active opportunistic infection. [2. AS PER
                          AMENDMENT 4/25/00: Uncompensated heart
                          failure or fluid overload.].
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0076  CD4-IgG
RESULTS                   MED/20521810. Shearer WT, Israel RJ, Starr S,
                          Fletcher CV, Wara D, Rathore M, Church J,
                          DeVille J, Fenton T, Graham B, Samson P,
                          Staprans S, McNamara J, Moye J, Maddon PJ,
                          Olson WC. J Infect Dis 2000
                          Dec;182(6):1774-9.
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Part 1: Single-dose
                          administration at 1 of 4 levels: 0.mg/kg, 1
                          mg/kg, 5 mg/kg, or 10 mg/kg. Part 2 [AS PER
                          AMENDMENT 4/25/00: Cohort I]: Doses
                          (estimated amg/kg) will be administered once
                          weekly at Weeks 0, 1, 2, and 3[AS PER
                          AMENDMENT 4/25/00: Part 2 - Cohort II:
                          20mg/kg once weeat Weeks 0, 1, 2, and 3.]
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intravenously
OTHER TREATMENT INFO.     TREATMENT DURATION: Part 1: Single-dose
                          administration with 14-day follow-up per dose
                          level. Part 2: Doses will be administered
                          once weekly at Weeks 0, 1, 2, and 3.
OTHER TREATMENT INFO.     END POINT: Maximum tolerated dose, toxicity,
                          pharmacokinetics, and efficacy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Specific Grade 3/4
                          toxicities. 2. Investigator determines that
                          further participation would be detrimental to
                          the patient's health or well-being. 3. Parent
                          or legal guardian refuses further treatment
                          and/or follow-up evaluations, or fails to
                          comply with the study requirements so as to
                          cause harm to the patient or seriously
                          interfere with the validity of the study
                          results. 4. Patient requires treatment with
                          medications that are disallowed on this
                          study. 5. Pregnancy.
OTHER TREATMENT INFO.     MODIFICATION: For Grade 1/2 toxicity, therapy
                          is continued as per protocol. For Grade 3
                          toxicity for single dosing (Part 1), infusion
                          is discontinued immediately. If toxicity
                          resolves within 60 minutes, infusion is
                          restarted at a 50% slower rate. If Grade 2 or
                          higher toxicity occurs at the same infusion,
                          therapy is permanently discontinued. For
                          multiple dosing (Part 2), if Grade 3 toxicity
                          resolves by the time of the next infusion,
                          the next infusion is started at full dose.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Children's Hosp of Los Angeles/UCLA Med Ctr
                          4650 Sunset Blvd Los Angeles, CA 900276016
                          Zane O'Keefe [phone] Recruiting 990915.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] No longer recruiting 001121.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 970909.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] Recruiting 990629.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          980821.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 990915.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 001006.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] No longer
                          recruiting 000829.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 971119.

8
UNIQUE IDENTIFIER         NIH/00875
PROTOCOL ID NUMBERS       NIAID ACTG 345
PROTOCOL TITLE            A Phase I/II Study of Ritonavir Therapy in
                          HIV-1 Infected Infants and Children.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Ram Yogev
PROTOCOL CHAIRS           CO-CHAIR  Ellen Chadwick
GENERAL DESCRIPTION       PURPOSE: To assess the pharmacokinetics,
                          safety, and tolerance of single and multiple
                          oral doses of ritonavir monotherapy, and in
                          combination with lamivudine (3TC) and
                          zidovudine (ZDV) in HIV-1 infected infants
                          and children; and any age-related differences
                          thereof. To ascertain a dose of ritonavir
                          which may be suitable for the Phase II/III
                          evaluation of ritonavir in combination with
                          3TC and ZDV in HIV-1 infected infants and
                          children younger than age 2. To evaluate the
                          antiretroviral activity and the immunological
                          effect of multiple doses of ritonavir
                          administered in combination therapy.
GENERAL DESCRIPTION       RATIONALE: As a group, vertically infected
                          children experience more rapid disease
                          progression than children infected at an
                          older age or adults. The early administration
                          of potent antiretroviral regimens might
                          significantly impact the course of vertical
                          HIV-1 infection.
GENERAL DESCRIPTION       METHODOLOGY: Infants and children are
                          stratified by age, representative of the
                          developmental differences related to drug
                          metabolism (Group I: at least 6 months - 2
                          years, Group II: 3-6 months, Group IIIA: 1
                          month - 10 weeks, IIIB: 1 month - less than 3
                          months). Within each age group there will be
                          two possible dosage cohorts. All age groups
                          will be enrolled simultaneously into dosage
                          Cohort I, at the initial drug dosage.
                          Progression to Cohort II (at a higher or
                          lower drug dosage) will be decided according
                          to safety, tolerance or viral load in Cohort
                          I. All therapy for Group I/II, whether in
                          Cohort I or II, will be introduced as
                          follows: single dose of ritonavir on Day 0,
                          ritonavir monotherapy through Day 7 AM and
                          combination therapy from Day 7 PM through
                          Week 104. All therapy for Group IIIA & IIIB,
                          whether in Cohort I or II, will be introduced
                          as follows: single dose of ritonavir on Day 0
                          AM and transition to combination therapy Day
                          0 PM through Week 104. NOTE: Progression to
                          combination therapy for Group IIIA infants is
                          dependent upon the results of the single-dose
                          ritonavir pharmacokinetics (PK). If the
                          patient is no longer at least presumed to be
                          HIV-infected, he/she will be discontinued
                          from the study. Replacement infants, who will
                          not receive the single dose of ritonavir,
                          will be acquired from Group IIIB infants; new
                          infants that are either presumed HIV infected
                          or have already been shown to be
                          HIV-infected. Clinical evaluations are
                          conducted and blood and urine samples
                          collected regularly during the treatment
                          period in order to quantify HIV-1 levels and
                          determine body chemistries. Pharmacokinetic
                          studies require additional blood sampling up
                          to Week 16. [AS PER AMENDMENT 6/30/98:
                          Pharmacokinetics data from Cohort I showed
                          that the proposed Cohort II starting dose was
                          too low. The dose for Cohort II is now
                          increased. All subjects in Groups I, II, and
                          III will begin combination therapy on Day 0
                          at the increased dose.] [AS PER AMENDMENT
                          3/13/00: The study has been extended for an
                          additional 104 weeks, provided the patient's
                          viral load is undetectable (below 400
                          copies/ml) at the end of the initial study
                          period. While on the treatment extension,
                          patients must continue their current schedule
                          for study drug administration and completion
                          of study visits.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination and single
                          pharmacokinetics, Combination and single drug
                          therapy, Drug safety, Drug tolerance,
                          Immunology, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients. 18-24 per
                          dose cohort. [AS PER AMENDMENT 3/13/00: The
                          enrollment of up to 12 additional patients
                          into Cohort II, Group III (infants 1-3 mo
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 104 weeks. [AS
                          PER AMENDMENT 3/13/00: This study has been
                          extended for an additional 104 weeks,
                          provided the patient's HIV RNA is
                          undetectable, below 400 copies/ml, at the end
                          of the initial 104-week study period.].
PROTOCOL DETAILS          ACTUAL ACCRUAL: 51/60 010321.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 33
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (000313)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 345
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Evidence of HIV infection for
                          patients 18 months or less, as demonstrated
                          by the following: Two positive viral tests
                          (culture, PCR, p24 antigen, ICDp24 antigen)
                          on two different blood specimens, one of
                          which must be a culture and one of the tests
                          must have been done at an ACTG-certified
                          laboratory. Patients older than 18 months
                          must have 2 or more separate specimens
                          positive for HIV-1 antibody by a
                          federally-licensed ELISA. At least one HIV-1
                          antibody test must be confirmed by IFA or
                          Western blot. Group III infants receiving
                          combination therapy: One positive HIV-1 DNA
                          PCR or culture, provided that a second blood
                          sample is sent at the entry visit for HIV-1
                          DNA PCR and culture. [AS PER AMENDMENT
                          3/13/00: Infants in Cohort II, Group III must
                          have two positive HIV-1 DNA PCRs or viral
                          cultures from two different blood specimens.]
                          2. CDC Category N, A, B, or C with [AS PER
                          AMENDMENT 3/13/00: or C and] Immunologic
                          Category 1 or 2 clinical infection. 3. Signed
                          informed consent from parent or legal
                          guardian.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 750 cells/mm3 (< 12
                          months) ( 750 - 800 - plus ), >= 500 (>= 1
                          year) ( 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x Norm NFA (Normal for Age).
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x Norm.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x Norm.
PATIENT INCLUSION CRIT.   CREATININE: < .8.
PATIENT INCLUSION CRIT.   OTHER: Sodium < 150 and > 130 mEq/L.
                          Potassium < 5.9 and > 3 mEq/L. Calcium < 11.3
                          and > 7.8 mEq/L. Blood glucose < 160 and > 55
                          mg/dl. Urine < 1+ protein and < 25 rbc.
PATIENT INCLUSION CRIT.   WEIGHT: Required: 3.5 kg or more.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: 1. Antiretroviral
                          monotherapy (excluding 3TC or protease
                          inhibitors) lasting less than 6 weeks,
                          regardless of RNA level at screening. 2.
                          Monotherapy (excluding 3TC or protease
                          inhibitors), or combination ZDV/d4T, ZDV/ddI,
                          or ZDV/ddC lasting 3 months or more, if
                          plasma RNA is above 10,000 copies/ml. [3. AS
                          PER AMENDMENT 3/13/00: Nevirapine, 1 week or
                          less for infants enrolling into Cohort II,
                          Group III.].
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. IVIG (in
                          infants at least 6 months old) and
                          corticosteroids for the treatment of
                          lymphocytic interstitial pneumonitis or an
                          autoimmune process. 2. Prophylaxis for PCP
                          and Mycobacterium avium complex. 3.
                          Antifungal medications for the treatment of
                          HIV-related conditions, such as mucosal
                          candidiasis or acyclovir for herpes simplex
                          or varicella zoster. 4. Blood products as
                          necessary. 5. Therapy from co-enrollment in
                          other protocols, but all Protocol Chairs must
                          be consulted. 6. Acetaminophen, aspirin, beta
                          blockers, diphenhydramine, heparin,
                          hydroxyzine, hydralazine, hydrocodone,
                          ibuprofen, lorazepam, morphine, and
                          procainamide. Allowed after Day 28 of the
                          study: 1. Alfentanil, calcium channel
                          blockers, carbamazepine, cimetidine,
                          dexamethasone, fentanyl, itraconazole,
                          ketoconazole, methadone, miconazole IV,
                          phenobarbital, phenytoin, rifampin,
                          theophylline, and valproate. The Protocol
                          Chair must consulted. Results from monitoring
                          or serum concentrations (if available) must
                          be recorded on the CRFs. 2. Routine pediatric
                          vaccines.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 01
                          months less than or equal to 02 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Known toxicity or intolerance to 3TC and/or
                          ZDV at the proposed dosages.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Antiretroviral
                          treatment for 6 to 12 weeks. Infants who have
                          received less than 6 weeks of antiretroviral
                          monotherapy (excluding 3TC or protease
                          inhibitors), regardless of plasma RNA at
                          screening, are allowed.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Routine
                          pediatric vaccines in the first 28 days of
                          the study. 2. Other investigational agents.
                          3. HIV-1 vaccines. 4. Antiretroviral therapy,
                          except as permitted for study inclusion. 4.
                          IVIG for infants less than 6 months of age.
                          5. Medications incompatible with ritonavir,
                          including, alprazolam, amiodarone, anticancer
                          agents, astemizole, bepridil, bupropion,
                          cisapride, clorazepate, clozapine,
                          cyclosporine, diazepam, disopyramide
                          phosphate, encainide hydrochloride,
                          ergotamine tartrate/dihydroergotamine
                          mesylate, estazolam, flecainide acetate,
                          flurazepam hydrochloride, indinavir,
                          meperidine hydrochloride, metronidazole,
                          midazolam hydrochloride, pimozide, piroxicam,
                          propafenone, propoxyphene, quinidine
                          sulphate, quinidine gluconate, quinidine
                          polygalacturonate, quinine sulphate,
                          rapamycin, rifabutin, saquinavir, tacrolimus,
                          terfenadine, triazolam, warfarin, and
                          zolpidem. 6. Alfentanil, calcium channel
                          blockers, carbamazepine, cimetidine,
                          dexamethasone, f
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions and symptoms are excluded: 1. Any
                          significant acute or chronic infections
                          requiring treatment during the study period.
                          2. Infants with clinical assessments of Grade
                          1 or higher, as defined in Appendix II of the
                          protocol. 3. AIDS-defining opportunistic
                          infection within 2 months prior to study
                          entry. 4. Wasting or failure to thrive, as
                          defined in the protocol. 5. Progressive
                          encephalopathy attributable to HIV as defined
                          in Appendix VI of the protocol. 6.
                          Malignancy. 7. Hypogammaglobulinemia. 8.
                          Nasogastric or gastric tubes. 9. Inability to
                          be followed by an ACTG center for the study
                          duration.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0244  Ritonavir
RESULTS                   Zhao Y, Vetterick T, Lewis D, Yu M, Chadwick
                          E, Yogev R, Coberly SK, Palumbo P. 8th Conf
                          Retro and Opportun Infect. 2001 Feb 4-8
                          (abstract no. 467).
RESULTS                   Scott ZA, Chadwick EG, Catalina MD, McManus
                          M, Yogev R, Palumbo P, Britto P, Sullivan JL,
                          Luzuriaga K. 8th Conf Retro and Opportun
                          Infect. 2001 Feb 4-8 (abstract no. 169).
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Day 7 (noon, 8 PM):
                          160 mg/mm2 q 8h. Day 8 - Week 104: 160 mg/mm2
                          q 8h. Drug 2: Day 7 PM: 4 mg/kg. Day 8 AM -
                          Week 104: 4 mg/kg q 12h. Drug 3: 350
                          mg/mm2/dose q 12h (Cohort I). [AS PER
                          AMENDMENT 6/3dose for Cohort II is now 450
                          mg/mm2/dose q 12h.]
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Day 7: 320 mg/mm2. Day
                          8 - Week 104: 480 mg/mm2. Drug 2: Day 7: 4
                          mg/kg. Day 8 - Week 104: 8 mg/kg. Drug 3: 700
                          mg/mm2 (Cohort I). [AS PER AMENDMENT 6/30/98:
                          Dailydosage for Cohort II is now 900 mg/mm2.]
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 104 weeks. [AS PER
                          AMENDMENT 3/13/00: This study has been
                          extended for an additional 104 weeks,
                          provided the patient's HIV RNA is
                          undetectable, below 400 copies/ml, at the end
                          of the initial 104-week study period. If the
                          patient's viral load is at least 400
                          copies/ml at the end of the initial 104-week
                          study period the child is not eligible to
                          continue on the study extension.].
OTHER TREATMENT INFO.     END POINT: Toxicity, virology, resistance.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Recurrent or
                          persistent (more than 7 days) [AS PER
                          AMENDMENT 3/13/00: (more than 14 days)] Grade
                          III toxicity or any Grade IV toxicity. 2.
                          Immunological deterioration as evidenced by a
                          drop in CD4 percentage of 50% or more of the
                          baseline value confirmed on at least two
                          measurements that are taken 1 week apart. 3.
                          There has not been a 1 log reduction or more
                          in viral load, confirmed by sequential
                          measurement within 2 weeks, after 1 month of
                          combination therapy. 4. There has been a 2
                          log reduction or more from the original viral
                          load, confirmed by sequential measurement
                          within 2 weeks and results obtained within 1
                          month, after 3 months of combination therapy.
                          5. One log rebound from virologic nadir,
                          confirmed by sequential measurement. 6.
                          Parent or legal guardian chooses to withdraw
                          patient, or is found to be repeatedly
                          noncompliant with protocol requirements. [7.
                          AS PER AMENDMENT 3/13/00: A viral load of 400
                          copies/ml or higher at the end of the initial
                          104-week study period will cause patients to
                          be ineligible for the 104-week study
                          extension.].
OTHER TREATMENT INFO.     MODIFICATION: Doses are modified for the
                          following reason: Specific toxicities. Within
                          each age group, the progression of the study
                          to Cohort II is decided according to
                          patients' tolerance (at any time) or viral
                          load (at 12 weeks of therapy), in Cohort I as
                          follows: 1. Unacceptable safety/tolerance at
                          any time, will close Cohort I completely.
                          Subsequent patients enrolled to this age
                          group will be in Cohort II, where there will
                          be a 20% decrease in ritonavir dose (3TC and
                          ZDV will remain at initial doses). 2. If
                          viral load is detectable in 2 patients,
                          confirmed by sequential measurement within 2
                          weeks, in a given age group of Cohort I at or
                          after 3 months of compliant combination
                          therapy, and toxicity is not an issue, Cohort
                          II will be opened for new enrollees, in this
                          age group, with a 20% increased ritonavir
                          dose.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 990915.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 990915.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 970912.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] Recruiting 990629.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 970806.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 970806.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] No longer
                          recruiting 000424.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] No longer recruiting 010123.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 970717.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          970725.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] No longer
                          recruiting 010130.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 980204.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 990915.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 990915.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Sue Lovelace [phone] No longer
                          recruiting 000829.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] No longer recruiting 010627.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 970619.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 970617.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 980930.
NEW YORK                  Cornell Univ Med College 1300 York Ave / PO
                          Box 296 New York, NY 10021 Kathleen O'Keefe
                          [phone] No longer recruiting 990203.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 970724.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 971003.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          990915.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010418.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 990719.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] No longer recruiting
                          010612.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone] No longer
                          recruiting 010717.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          990915.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone] No
                          longer recruiting 000817.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          970630.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 990723.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone] No
                          longer recruiting 000203.

9
UNIQUE IDENTIFIER         NIH/00867
PROTOCOL ID NUMBERS       CC 97 I-082
PROTOCOL TITLE            Use of Combination Antiviral Therapy to
                          Delineate the Identity and Longevity of
                          Persistent Reservoirs of HIV-1 Infection.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To define the reservoirs (sites in
                          the body) of persistent HIV-1 infection in
                          the setting of antiviral therapy and the
                          ability of the virus to infect new target
                          cells. To determine if any of these potential
                          reservoirs contribute to persistent HIV-1
                          infection, and whether antiviral therapy can
                          reverse the effects of HIV infection on CD4+
                          cell responses, lymph node structure, and
                          skin testing. To determine the rates of HIV-1
                          virus load and CD4+ cell turnover in patients
                          with more than 500 and in patients with less
                          than 300 CD4+ cells. [AS PER AMENDMENT
                          2/4/98: To define reservoirs of persistent
                          HIV-1 infection in the setting of antiviral
                          therapy and the ability of the virus to
                          infect new target cells. Define the longevity
                          of persistent reservoirs of HIV-1 infection.
                          Determine whether the turnover of potential
                          persistent reservoirs of infection can be
                          accelerated through administration of an
                          intravenous steroid preparation with potent
                          antiviral medication. Determine the rates of
                          HIV-1 virus load and CD4+ cell turnover.
                          Determine whether important aspects of
                          HIV-1-induced proliferative responses and T
                          cell antigen receptor repertoire and the
                          disruption of lymphoid tissue architecture
                          can be reversed by active suppression of
                          HIV-1 replication by a potent combination of
                          antiviral medications.]
GENERAL DESCRIPTION       RATIONALE: Recent treatment with combination
                          antiretroviral therapy has been shown to
                          bring levels of HIV-1 to undetectable levels
                          in the bloodstream, but the reservoirs of
                          persistent HIV-1 infection in other locations
                          in the body are currently unknown.
GENERAL DESCRIPTION       METHODOLOGY: Two groups of patients [AS PER
                          AMENDMENT 2/4/98: three groups stratified by
                          CD4 count (less than 300 cells/mm3, 300-500
                          cells/mm3, and greater than 500 cells/mm3)]
                          receive zidovudine (AZT), lamivudine (3TC),
                          indinavir, and nevirapine therapy for at
                          least 12 months. Five patients with a CD4
                          count greater than 500 receive a steroid
                          intravenously for five days in an attempt to
                          mobilize HIV-1 trapped within lymphoid tissue
                          to hasten the depletion of total body viral
                          load.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 1
                          year.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (980204)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Parallel Designs
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection, as documented by
                          ELISA and confirmed by Western blot. 2. Two
                          CD4+ cell counts of 500 cells/mm3 or more, or
                          two CD4+ cell counts of 300 cells/mm3 or
                          less. [AS PER AMENDMENT 2/4/98: Patients with
                          CD4+ cell counts of greater than 500, between
                          300 and 500, and less than 300 cells/mm3 are
                          eligible.] 3. Three or more palpable lymph
                          nodes. 4. No significant cardiac, pulmonary,
                          kidney, rheumatologic, gastrointestinal,
                          psychiatric, or neurological diseases. 5. No
                          known underlying bleeding disorder. 6. Plasma
                          HIV RNA levels greater than 8,000 copies/ml.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 100000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Three groups based on
                          CD4+ cell count (<300, 300-500, and >500).
PATIENT INCLUSION CRIT.   CREATININE: < 2.
PATIENT INCLUSION CRIT.   OTHER: Plasma HIV-RNA > 8,000. Liver function
                          tests < 1.5 X normal values. PT or PTT not
                          prolonged by more than 2 seconds.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with CD4
                          cell counts of 500 cells/mm3 or more with the
                          following symptoms or conditions are
                          excluded: 1. History of adverse reactions to
                          systemic corticosteroid administration. 2.
                          History of glaucoma. 3. Symptoms of
                          significant HIV-related illnesses [AS PER
                          AMENDMENT 2/4/98: Patients with CD4 cell
                          counts greater than 300 are excluded].
                          Patients with CD4 cell counts of 300
                          cells/mm3 or less with the following symptoms
                          or conditions are excluded: Active
                          opportunistic infections.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current or past
                          substance abuse that might interfere with
                          protocol compliance or compromise patient
                          safety.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: For those with
                          CD4 counts of 500 cells/mm3 or more: 1. Prior
                          antiretroviral therapy [AS PER AMENDMENT
                          2/4/98: Patients with CD4 cell counts greater
                          than 300 cells/mm3 are excluded]. 2. Therapy
                          with systemic corticosteroids, experimental
                          medication, or chemotherapy within previous 6
                          months. For patients with CD4 counts of 300
                          cells/mm3 or less: 3TC, nevirapine, or
                          protease inhibitors.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Medical contraindication to lymph node
                          biopsy. 2. Psychiatric illness that might
                          interfere with study compliance or be
                          exacerbated by corticosteroid treatment.
                          Patients with CD4+ cells greater than 500
                          cells/mm3 who have any of the following
                          symptoms or conditions are excluded: 1.
                          Active peptic ulcer disease. 2. Diabetes.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0004  Zidovudine
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 1 year.
OTHER TREATMENT INFO.     END POINT: Definition and longevity of the
                          reservoirs (sites in body) of persistent
                          HIV-1 infection, effect of antiviral therapy
                          in reversing the effects of HIV-1 infection,
                          and the rates of HIV-1 virus load and CD4+
                          cell turnover in patients with more than 500
                          and those with less than 300 CD4+ cells. [AS
                          PER AMENDMENT 2/4/98: Definition and
                          longevity of the reservoirs of persistent
                          HIV-1 infection, effect of steroid/antiviral
                          therapy on acceleration of potential disease
                          reservoir turnover, rate of HIV-1 virus load
                          and CD4+ cell turnover, and the effect of
                          antiviral therapy on HIV-1-induced
                          proliferative response, T cell antigen
                          receptor repertoire, and disruption of
                          lymphoid tissue architecture.].
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 970805.

10
UNIQUE IDENTIFIER         NIH/00863
PROTOCOL ID NUMBERS       CC 96 C-0113
PROTOCOL TITLE            A Pilot Study of IL-12 as an
                          Anti-Angiogenesis Agent and Immunostimulator
                          in Patients with Kaposi's Sarcoma.
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: This protocol's purpose is to test
                          the possible utility of the cytokine
                          interleukin-12 (IL-12) in the treatment of
                          Kaposi's sarcoma (KS).
GENERAL DESCRIPTION       RATIONALE: IL-12 is a cytokine that plays an
                          important role in T cell development in the
                          body. It particularly enhances the
                          development of TH1 (cellular) immune
                          responses. HIV-infected patients are usually
                          deficient in IL-12 production and have a
                          particular defect in TH1 immune responses.
                          IL-12 has also been shown to block
                          angiogenesis (new blood vessel formation) and
                          for this reason is being tested for possible
                          use in the treatment of KS.
GENERAL DESCRIPTION       METHODOLOGY: This clinical trial involves the
                          administration of IL-12 to patients for 12
                          weeks or (if they appear to be responding)
                          for up to 1 year. The drug will be given by
                          needle subcutaneously twice weekly. Patients
                          will be observed for an effect of the IL-12
                          on their KS and for improvement in their
                          immune function.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 weeks to 1
                          year.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: Sarcoma, Kaposi.
PROTOCOL DETAILS          STUDY DESIGN: Open Label
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Non-life threatening KS.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Patients
                          must be taking at least 2 anti-retroviral
                          drugs.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Patients must be
                          off all other therapies for KS for at least 3
                          weeks prior to entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Other KS
                          therapy within 3 weeks of study entry and
                          during study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with any of the
                          following symptoms or conditions are
                          excluded: 1. Pulmonary KS. 2. Other
                          life-threatening KS.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0259  Interleukin-12
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Patients will be
                          treated twice weekly
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneously
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 weeks to 1 year.
OTHER TREATMENT INFO.     END POINT: Efficacy and improvement in immune
                          functions.
SUPPORTING AGENCY         Natl Cancer Institute.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 010111.

11
UNIQUE IDENTIFIER         NIH/00828
PROTOCOL ID NUMBERS       NIAID ACTG 321
PROTOCOL TITLE            Phase I Study of Safety, Tolerance, and
                          Pharmacokinetics of Abacavir (1592U89, ABC)
                          With Standard Zidovudine (ZDV) Therapy In
                          Neonates Born to HIV-1 Infected Women.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  George Johnson
PROTOCOL CHAIRS           CO-CHAIR  Andrew Wiznia
GENERAL DESCRIPTION       PURPOSE: For single-dose arms: To evaluate
                          the single oral dose pharmacokinetic profile
                          of abacavir (ABC, 1592U89) and to determine
                          the acute toxicity of single-dose
                          administration of ABC in HIV-1 exposed
                          infants. For multiple-dose arm: To evaluate
                          6-week pharmacokinetics, safety, and
                          tolerance of multiple oral doses of ABC in
                          combination with zidovudine (ZDV) in HIV-1
                          exposed infants receiving standard postnatal
                          ZDV treatment. To determine potential within
                          patient of age-related differences in the
                          pharmacokinetics, safety, and tolerance of
                          multiple oral doses of ABC in combination
                          with ZDV in HIV-1-exposed infants receiving
                          standard postnatal ZDV treatment. To
                          determine dosages of ABC that may be suitable
                          for Phase II/III evaluation of ABC in
                          combination with ZDV as early therapy in
                          HIV-infected infants and for postnatal dosing
                          in perinatal studies.
GENERAL DESCRIPTION       RATIONALE: The rationale for investigation of
                          this agent is to define the safety and
                          pharmacokinetics in young infants to allow
                          for investigation of the efficacy of this
                          agent in combination with ZDV as potential
                          early therapy in newborn and young infants.
                          The rationale for early aggressive therapy is
                          that this may be the best chance to
                          significantly reduce the long-term
                          progression and subsequent impact of HIV-1
                          infection in vertically infected infants.
                          Early ablation or enhanced suppression of
                          HIV-1 replication may significantly reduce
                          total viral load and may allow maturation,
                          preservation, or reconstruction of immune
                          function at a stage early in infection
                          providing improved control of HIV-1 infection
                          and reduced disease progression.
GENERAL DESCRIPTION       METHODOLOGY: This study is divided into 3
                          sections, as follows: Part 1A is a
                          single-dose study in neonates 0 to 72 hours
                          of age. If four of four patients reach the
                          minimal therapeutic level with less than
                          Grade 3 toxicity, the ABC dose is escalated.
                          Part 1B is also a single-dose study in
                          infants 21 to 28 days of age, starting with
                          the dose identified in Part 1A. If four of
                          four patients reach the minimal therapeutic
                          level with less than Grade 3 toxicity, the
                          dose is escalated again. Finally, Part 2 is a
                          multi-dose study to examine a dosing regimen
                          for ABC and ZDV for neonates 0 to 72 hours of
                          age. The dosing regimen for ABC is the dose
                          defined in Part 1A for the first 3 weeks (0
                          to 3 weeks of age) followed by the dose
                          defined in Part 1B for the second 3 weeks (3
                          to 6 weeks of age). All patients receive 6
                          weeks of standard ZDV therapy. [AS PER
                          AMENDMENT 9/24/97: This study is divided into
                          sections, as follows: Part 1A is a
                          single-dose study in neonates 0 to 48 hours
                          of age. ABC dose escalations are made until a
                          dose is identified that meets toxicity
                          guidelines and demonstrates a minimal target
                          area under the concentration curve (AUC) of
                          2,000 ng-hr/ml. Part 1B is a similar
                          single-dose study in infants 3 to 7 days of
                          age with escalation as per part 1A. Part 1C
                          is an identical single-dose study in infants
                          21 to 28 days of age but starting at the dose
                          identified in Part 1B. Part 2 is a multi-dose
                          study to examine a 6-week dosing regimen for
                          ABC and ZDV for infants 0 to 48 hours of age.
                          The dosing regimen for ABC is defined in Part
                          1A for the first 48 hours of life, the dose
                          defined in Part 1B for Days 3 through 20 of
                          life, and the dose defined in Part 1C for
                          Days 21 through 42 of life.] [AS PER
                          AMENDMENT 7/29/98: Enrollment to Parts 1A and
                          1B will remain open; Part 1A will enroll a
                          minimum of 4 patients as planned, and Part 1B
                          will enroll 3 additional patients.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Pharmacokinetics, Drug toxicity.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients. [Accrual
                          amended AS PER AMENDMENT 9/24/97.].
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 weeks plus
                          follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 20/60 010116.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 14
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (980729)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 321
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Mothers must: 1.
                          Be HIV-infected. 2. Have estimated
                          gestational age of 37 weeks or more. 3. Have
                          ability to provide written informed consent
                          for infant and willingness to comply with
                          study requirements. Infants must have: 1. For
                          Parts 1A and 2: Age between birth and 72
                          hours old. For Part 1B: Age between 21 and 28
                          days old. [AS PER AMENDMENT 9/24/97: For
                          Parts 1A and C: Age between birth and 48
                          hours old. For Part 1B: Age between 3 and 7
                          days old. For Part 1C: Age between 21 and 28
                          days old.] 2. Absence at entry of any serious
                          infections requiring treatment during the
                          study period. 3. Neonatal dosing of ZDV.
                          Maternal administration of an antenatal and
                          intrapartum regimen is encouraged but not
                          required. 4. For Part 1B [AS PER AMENDMENT
                          9/24/97: Parts 1B and 1C]: Stable ZDV
                          therapy. 5. Ability to tolerate oral feeding.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: For infant:
                          Routine antibiotic management of common
                          infant infections. Other medications must be
                          approved by the protocol chair. Required: 1.
                          Neonatal dosing of ZDV. 2. Stable ZDV therapy
                          during Part 1B [AS PER AMENDMENT 9/24/97: and
                          Part 1C].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 01 days
                          less than or equal to 28 days.s.

PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: For mothers:
                          Antiretroviral agents (other than nucleoside
                          analogues) such as protease inhibitors and
                          nonnucleoside reverse transcriptase
                          inhibitors (NNRTIs). [AS PER AMENDMENT
                          7/29/98: NNRTIs may preclude enrollment but
                          generally are allowed and are not an absolute
                          exclusion. Eligibility is determined on a
                          case-by-case basis when an infant has been
                          exposed in utero to antiretroviral agents
                          other than nucleoside analogues.] For
                          infants: Exposure in utero to antiviral
                          agents (other than nucleoside analogues) such
                          as protease inhibitors and NNRTIs. [AS PER
                          AMENDMENT 7/29/98: NNRTIs may preclude
                          enrollment but generally are allowed and are
                          not an absolute exclusion. Eligibility is
                          determined on a case-by-case basis when an
                          infant has been exposed in utero to
                          antiretroviral agents other than nucleoside
                          analogues.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: For infants:
                          1. Antiretroviral agents other than those
                          administered through this protocol, other
                          investigational agents, immunomodulators,
                          HIV-1 vaccines, glucocorticoids, drugs with
                          theoretical or known adverse interaction with
                          ZDV or ABC in vivo or ABC in serum or plasma.
                          2. Biological response modifier. 3. Human
                          growth hormone. 4. Probenecid and IV
                          pentamidine.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: For
                          infants: 1. Major congenital anomalies. 2.
                          Grade 2 or higher laboratory or clinical
                          toxicity at screening. 3. Inability to
                          receive follow-up at an ACTG center for the
                          duration of this trial.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
RESULTS                   AIDS/96920632. McKinney RE Jr. Conf
                          Retroviruses Opportunistic Infect. 1996 Jan
                          28-Feb 1;3rd:173.
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Part 1A: Single dose
                          of 1592U89 2 mg/kg po, subject to escalation.
                          Part 1B: Single dose of 1592U89 as defined in
                          Part Part 2: Dose as defined by Parts 1A and
                          1B po q12h until 42 dayage. AS PER AMENDMENT
                          9/24/97: Part 1C: Single dose of 1592U89
                          defined in Part 1B. Part 2: Dose as defined
                          by Part 1A for firshours, Part 1B for Days 3
                          through 20, and Part 1C for Days 21 through
                          42. Drug 2: 2 mg/kg po q6h until 42 days of
                          age
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Not applicable. Drug 2:
                          8 mg/kg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 2 weeks.
OTHER TREATMENT INFO.     END POINT: Pharmacokinetics, safety and
                          tolerance.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. The patient's legal
                          guardian refuses further treatment and/or
                          follow-up evaluations. 2. The investigator
                          determines that further participation would
                          be detrimental to the patient's health or
                          well-being. 3. The patient requires treatment
                          with medications which are disallowed while
                          on this study. 4. Unacceptable toxicity.
OTHER TREATMENT INFO.     MODIFICATION: Doses will be modified or
                          reduced for specific toxicities.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] No longer
                          recruiting 991210.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 980116.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          No longer recruiting 001213.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] Recruiting 980116.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          980116.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] No longer recruiting 010123.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] Recruiting
                          980116.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] No longer recruiting
                          000127.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone] No
                          longer recruiting 001121.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          980116.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 990716.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          980116.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 980116.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone]
                          Recruiting 980116.

12
UNIQUE IDENTIFIER         NIH/00783
PROTOCOL ID NUMBERS       CC 96 HG-51
PROTOCOL TITLE            Gene Therapy for AIDS Using Retroviral
                          Mediated Gene Transfer to Deliver HIV-1
                          Anti-Sense TAR and Transdominant Rev Protein
                          Genes to Syngeneic Lymphocytes in HIV-1
                          Infected Identical Twins.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety, cell
                          survival, and potential anti-HIV activity of
                          CD4+ lymphocytes (T4 cells) that have been
                          obtained from the uninfected, healthy
                          identical twin of an HIV-infected patient,
                          then culture-expanded and genetically
                          engineered with anti-HIV-1 genes (antisense
                          trans-activation-responsive [TAR] region and
                          transdominant Rev) before transfusion into
                          the HIV-infected twin. Methodology: Healthy
                          CD4+ lymphocytes are obtained from the
                          uninfected identical twin of an HIV-infected
                          patient. Cells are expanded in culture for
                          approximately 10 days, activated to increase
                          their function, and genetically altered with
                          both a marker gene (Neomycin resistance gene)
                          and anti-HIV-1 genes (antisense TAR and
                          transdominant Rev) that are theoretically
                          designed to provide intracellular protection
                          against HIV-1. HIV-infected recipients
                          receive the genetically-engineered cells via
                          intravenous infusion. The relative survival
                          of the engineered T cells is monitored by
                          vector-specific PCR, and the timing of the
                          second infusion is determined by when the
                          signal becomes undetectable, which varies
                          from patient to patient. The recipients'
                          functional immune status is monitored by
                          standard in vitro and in vivo testing
                          protocols. Patients receive a total of four
                          infusions at 8-week intervals, with weekly
                          clinic visits.
GENERAL DESCRIPTION       METHODOLOGY: Healthy CD4+ lymphocytes are
                          obtained from the uninfected identical twin
                          of an HIV-infected patient. Cells are
                          expanded in culture for approximately 10
                          days, activated to increase their function,
                          and genetically altered with both a marker
                          gene (Neomycin resistance gene) and
                          anti-HIV-1 genes (antisense TAR and
                          transdominant Rev) that are theoretically
                          designed to provide intracellular protection
                          against HIV-1. HIV-infected recipients
                          receive the genetically-engineered cells via
                          intravenous infusion. The relative survival
                          of the engineered T cells is monitored by
                          vector-specific PCR, and the timing of the
                          second infusion is determined by when the
                          signal becomes undetectable, which varies
                          from patient to patient. The recipients'
                          functional immune status is monitored by
                          standard in vitro and in vivo testing
                          protocols. Patients receive a total of four
                          infusions at 8-week intervals, with weekly
                          clinic visits.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Immunotherapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          STUDY DURATION: 12 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (960412)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Twin Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Recipients must
                          have: 1. HIV seropositivity. 2. CD4 cell
                          count greater than 50 cells/mm3. 3. A
                          healthy, HIV-seronegative identical twin
                          donor who is available for apheresis
                          throughout the study. 4. Life expectancy of
                          greater than 3 months. 5. Willingness to
                          comply with current NIH Clinical Center
                          guidelines concerning appropriate
                          notification of all current sexual partners
                          of an individual regarding his/her HIV-1
                          positive serostatus and the risk of
                          transmission of HIV-1 infection. 6. Strong
                          relationship with a private physician or
                          health-care provider at home who has
                          demonstrated close involvement in the
                          patient's care to date and who would be
                          willing to help supervise a patient's care
                          during each home subcutaneous interleukin-2
                          (scIL-2) cycle. 7. Reasonable access at home
                          to emergency medical services and a nearby
                          medical facility in the event of a medical
                          crisis. 8. Demonstrated reliability and
                          consistency in sterile technique, the
                          reconstitution of IL-2 vials, and the
                          administration of scIL-2 injections. 9.
                          Access to a reliable home weight scale and be
                          able to weigh themselves accurately on a
                          daily basis for the purposes of safety
                          monitoring. 10. Easy access to a telephone.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 50 cells/mm3 ( 51 -
                          100 - 200 - 300 - 400 - 500 - 600 - 700 - 800
                          - plus ).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required for recipient
                          twin: Enrollment and good standing on a
                          current NIAID protocol involving the use of
                          IL-2 therapy. The patient must already have
                          undergone at least one year of treatment on
                          the protocol during which IL-2 therapy has
                          been given, including at least two
                          well-tolerated outpatient cycles of scIL-2 at
                          a stable dose. The patient also must have a
                          history of generally tolerable side effects
                          while receiving IL-2 (i.e., did not require
                          frequent medical interventions, intravenous
                          fluid replacement, and/or IL-2 dose
                          reductions) and must not have experienced any
                          serious (Grade 3 or higher) clinical or
                          laboratory abnormalities of medical
                          significance during Days 0 to
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required for recipient
                          twin: 1. Treatment with FDA-approved and/or
                          expanded access antiretroviral agent(s) for
                          patients with baseline CD4 counts below 500
                          cells/mm3. Patients with baseline CD4 counts
                          above 500 cells/mm3 are eligible to receive
                          cell therapy on this protocol, but must be
                          treated with antiretroviral therapy if
                          evidence of significant and persistent viral
                          activation occurs in association with a cell
                          infusion. Significant and persistent viral
                          activation is defined as a 50% or greater
                          increase above baseline in any virologic
                          parameter for at least 2 consecutive weeks.
                          2. Receiving outpatient scIL-2 cycles at
                          least once every 6 months as part of their
                          normal protocol participation, except at the
                          discretion of the study team.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Recipients with
                          the following prior condition are excluded:
                          History of lymphoma.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Recent history of
                          substance abuse unless evidence is provided
                          of an ongoing therapeutic intervention (i.e.,
                          medical therapy or counseling) to control
                          such abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded in recipient twin:
                          Systemic therapy for biopsy-proven Kaposi's
                          sarcoma within 4 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Recipients with the following
                          symptoms or conditions are excluded: 1. Acute
                          or acutely progressing disease processes. 2.
                          Serious psychological or emotional illness.
                          3. Lymphoma. Donor twins with the following
                          symptoms or conditions are excluded: 1.
                          Untreated or inadequately treated medical
                          condition (e.g., cardiopulmonary disease,
                          acute infection) that, in the judgment of the
                          principal investigator, precludes apheresis.
                          2. Seropositivity for Epstein-Barr virus,
                          cytomegalovirus, hepatitis B, or hepatitis C,
                          if and only if the recipient twin tests
                          seronegative for the corresponding virus.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0146  Lymphocytes, Activated
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Four infusions at
                          8-week intervals
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intravenous (IV)
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 970805.

13
UNIQUE IDENTIFIER         FDA/00766
PROTOCOL ID NUMBERS       FDA 253B
PROTOCOL TITLE            Open-Label Compassionate Use of Nitazoxanide
                          for the Treatment of Cryptosporidiosis in
                          AIDS Patients.
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To provide a means by which AIDS
                          patients with cryptosporidiosis who cannot
                          participate in the ongoing, controlled
                          studies can be treated with nitazoxanide. To
                          collect data on the safety and effectiveness
                          of this drug. Methodology: Patients receive
                          oral nitazoxanide daily for 14 days, after
                          which those with complete clinical and
                          parasitologic response discontinue treatment.
                          Non-responders and partial responders may
                          continue therapy for an additional 14 days at
                          the discretion of the physician.
                          Non-responders who show signs of improvement
                          or who have partial response after 28 days
                          and those who relapse following complete
                          response may continue therapy for an
                          additional month, up to 60 days total. [AS
                          PER AMENDMENT 10/30/96: Patients receive a
                          daily treatment for 4 weeks, with subsequent
                          dose escalation in the absence of
                          drug-related toxicity. Patients who exhibit
                          complete response after 2 months may continue
                          at a maintenance dose. Patients enrolled
                          after October 15, 1996 are randomized to 1 of
                          2 doses, with subsequent escalations made in
                          the absence of toxicity. Complete responders
                          may continue therapy at a maintenance dose
                          and duration determined by the investigator.
                          Non-responders after 6 months of therapy have
                          treatment discontinued.] [AS PER AMENDMENT
                          8/5/97: All patients are evaluated at Weeks
                          1, 2, 4, and monthly thereafter.] [AS PER
                          AMENDMENT 8/17/99: New patients start therapy
                          on a different dosage of nitazoxanide. Those
                          who do not respond after 4 weeks of therapy
                          will escalate to a higher dosage. Patients
                          who show a complete response at 2 consecutive
                          visits (2 weeks apart) discontinue
                          nitazoxanide therapy and go to follow-up.]
                          [AS PER AMENDMENT 2/3/00: The Week 1 clinical
                          evaluation is deleted from the study
                          procedures.].
GENERAL DESCRIPTION       METHODOLOGY: Patients receive oral
                          nitazoxanide daily for 14 days, after which
                          those with complete clinical and
                          parasitologic response discontinue treatment.
                          Non-responders and partial responders may
                          continue therapy for an additional 14 days at
                          the discretion of the physician.
                          Non-responders who show signs of improvement
                          or who have partial response after 28 days
                          and those who relapse following complete
                          response may continue therapy for an
                          additional month, up to 60 days total. [AS
                          PER AMENDMENT 10/30/96: Patients receive a
                          daily treatment for 4 weeks, with subsequent
                          dose escalation in the absence of
                          drug-related toxicity. Patients who exhibit
                          complete response after 2 months may continue
                          at a maintenance dose. Patients enrolled
                          after October 15, 1996 are randomized to 1 of
                          2 doses, with subsequent escalations made in
                          the absence of toxicity. Complete responders
                          may continue therapy at a maintenance dose
                          and duration determined by the investigator.
                          Non-responders after 6 months of therapy have
                          treatment discontinued.] [AS PER AMENDMENT
                          8/5/97: All patients are evaluated at Weeks
                          1, 2, 4, and monthly thereafter.] [AS PER
                          AMENDMENT 8/17/99: New patients start therapy
                          on a different dosage of nitazoxanide. Those
                          who do not respond after 4 weeks of therapy
                          will escalate to a higher dosage. Patients
                          who show a complete response at 2 consecutive
                          visits (2 weeks apart) discontinue
                          nitazoxanide therapy and go to follow-up.]
                          [AS PER AMENDMENT 2/3/00: The Week 1 clinical
                          evaluation is deleted from the study
                          procedures.].
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010605)
PROTOCOL DETAILS          STUDY INTENT: Compassionate use.
PROTOCOL DETAILS          PROJECTED ACCRUAL: UNLIMITED patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At discretion
                          of investigator for complete responders (up
                          to 6 months for non-responders).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (000203)
PROTOCOL DETAILS          DISEASE STUDIED: Cryptosporidiosis.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: UMD-95-009
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. Refractory cryptosporidial
                          diarrhea. 3. No history of intestinal
                          Mycobacterium avium-intracellulare infection
                          or intestinal Kaposi's sarcoma.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 200 cells/mm3 ( 0 -
                          100 - 200 ). > 200 cells/mm3 is allowed ONLY
                          IF patient has had symptomatic
                          cryptosporidiosis for at least 4 weeks. ( 201
                          - 300 - 400 - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test within 14 days of study entry Abstinence
                          or effective method of birth control /
                          contraception including oral contraceptives
                          during the study Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Prophylaxis
                          or maintenance for opportunistic infections,
                          provided dosage regimen has been stable for
                          at least 2 weeks prior to study entry.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 03
                          years less than or equal to 65 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of Cytomegalovirus colitis unless 28
                          days of therapy with ganciclovir or foscarnet
                          were completed prior to diagnosis of
                          cryptosporidiosis.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Investigational
                          drug therapy within 14 days prior to study
                          entry, unless available under FDA-authorized
                          expanded access program.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Drugs
                          with possible anti-cryptosporidial activity,
                          such as paromomycin, spiramycin,
                          azithromycin, clarithromycin, hyperimmune
                          bovine colostrum. 2. Experimental agents used
                          to treat microsporidiosis, such as
                          albendazole.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded:
                          Salmonella, Shigella, Campylobacter,
                          Yersinia, Giardia lamblia, Entamoeba
                          histolytica, Isospora, Cyclospora, or
                          Clostridium difficile toxin in stool.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0242  Nitazoxanide
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 500 mg bid (7.5
                          mg/kg bid in children) for at least 14 [AS
                          PER AMENDMENT 10/15/96: 1000 or 2000 mg (15
                          or 30 mg/kg fochildren).] [AS PER AMENDMENT
                          8/5/97: 500 or 1000 or 1500 mg (7.5, 15, 22.5
                          mg/kg, bid for children).] [AS PER AMENDMENT
                          8/11000 or 1500 mg bid (15 or 22.5 mg/kg, bid
                          for children).]
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 1000 mg (15 mg/kg in
                          children). [AS PER AMENDMENT 10/11000 or 2000
                          mg (15 or 30 mg/kg for children).] [AS PER
                          AMENDM8/5/97: 1000 or 2000 or 3000 mg (15 or
                          30 or 45 mg/kg for children).] [AS PER
                          AMENDMENT 8/17/99: 2000 or 3000 mg (30 or
                          4mg/kg for children).]
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 500-mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: At discretion of
                          investigator for complete responders (up to 6
                          months for non-responders).
SUPPORTING AGENCY         Romark Laboratories LC.
LAST REVISION DATE        20010605
FLORIDA                   Romark Laboratories LC 6200 Courtney Campbell
                          Causeway Tampa, FL 33607 Julie Ryner
                          [phone] Recruiting 990805.

14
UNIQUE IDENTIFIER         NIH/00755
PROTOCOL ID NUMBERS       NIAID ACTG 265
PROTOCOL TITLE            Phase I/II Study of the Safety and
                          Immunogenicity of Live-Attenuated Varicella
                          Vaccine (Varivax) in HIV-Infected Children.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety [AS PER
                          AMENDMENT 9/9/99: the following text has been
                          deleted: and immunogenicity] of
                          live-attenuated varicella vaccine in 3 groups
                          of VZV-naive, HIV-infected children] of
                          live-attenuated varicella vaccine in
                          VZV-naive, asymptomatic or mildly symptomatic
                          HIV-infected children ages 12 to 48 months
                          [AS PER AMENDMENT 7/2/96: children 1 to 8
                          years of age] [AS PER AMENDMENT 5/21/01: (1)
                          asymptomatic or mildly symptomatic cohort:
                          Group I (accrual complete); (2) symptomatic
                          cohort: Group II: patients classified at
                          stage B1, A2, N2, or B2 at study entry; (3)
                          symptomatic cohort: Group III patients
                          previously classified at immunologic stage 3,
                          but are at Category A1 or N1 (and on stable
                          antiretroviral therapy) at entry and for 3
                          months prior to entry]. To monitor the
                          short-term local and systemic reactions
                          following administration of live-attenuated
                          varicella vaccine. To monitor clinical and
                          immunologic progression of HIV in children
                          who have received varicella vaccine.
GENERAL DESCRIPTION       RATIONALE: Primary varicella infection, or
                          chickenpox, can be devastating to
                          HIV-infected children because complications
                          occur at higher rates in immunocompromised
                          hosts. Current passive prophylaxis measures
                          with varicella-zoster immune globulin are
                          suboptimal because administration must be
                          repeated for each exposure during the child's
                          lifetime and timely notification of exposure
                          is not always possible. Since Varivax has
                          been licensed for routine vaccination of
                          healthy individuals, it must be determined
                          whether this vaccine can be safely
                          administered to HIV-infected children.
GENERAL DESCRIPTION       METHODOLOGY: Thirty-six children who are
                          varicella zoster virus (VZV)-naive (treatment
                          group) receive Varivax at Weeks 0 and 12,
                          with a possible boost at Week 52 if the
                          patient is still seronegative for VZV and
                          cytomegalovirus infection. Twenty children
                          who have a history of wild-type varicella
                          exposure within the past year (control group)
                          receive no study treatment. All patients are
                          either asymptomatic or mildly symptomatic for
                          HIV infection. Patients make 12-14 visits to
                          the clinic. [AS PER AMENDMENT 9/9/99: This
                          study has been reorganized into two cohorts
                          (asymptomatic and symptomatic). In the
                          asymptomatic cohort, accrual has been
                          completed with 40 patients in Treatment Group
                          I and 19 in the control group. This phase of
                          the study demonstrated that Varivax was well
                          tolerated in 48 HIV-infected children with
                          asymptomatic disease. The symptomatic cohort
                          includes Treatment Groups II and III, each
                          with 30 patients. The first 10 patients from
                          Group II are monitored for 42 days following
                          the first dose of vaccine before the
                          remaining 20 are accrued. Once the first 10
                          patients in Group II have been evaluated with
                          acceptable toxicity and immunologic profiles,
                          the remaining 20 Group II and the first 10
                          Group III patients are enrolled. The first 10
                          Group III patients are also followed for
                          acceptable toxicity and immunologic response
                          before accrual of the remaining 20 Group III
                          patients.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Immunology,
                          Vaccine prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 127 patients. 36 in
                          treatment group and 20 in control group. [AS
                          PER AMENDMENT 9/9/99: 48 in Treatment Group
                          I, 19 in control group, and 30 each in Tre
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 108/127 010712.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 48
PROTOCOL DETAILS          VERSION NUMBER & DATE: 4 (010521)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 265
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection, as documented by two
                          of the following: (1) DNA PCR or HIV culture
                          at any age [AS PER AMENDMENT 5/21/01: (with
                          viral load greater than 10,000 copies/ml)],
                          (2) p24 antigen detection after Week 4 of
                          life, or (3) ELISA with confirmatory Western
                          blot after 10 [AS PER AMENDMENT 5/21/01: 18]
                          months of life. 2. Category N1 or A1
                          clinical/immunologic status [AS PER AMENDMENT
                          9/9/99: Control group and Treatment Group I
                          only. Patients in the control group must have
                          category N1 or A1 clinical/immunologic status
                          within 3 months prior to varicella
                          infection]. 3. Parent or legal guardian to
                          sign a written informed consent. Patients in
                          the control group must have: 1. Clinically
                          confirmed diagnosis of varicella infection
                          within the past 12 months. 2. Category N1 or
                          A1 clinical/immunologic status within 3
                          months prior to varicella infection. [AS PER
                          AMENDMENT 9/9/99: Patients in Treatment Group
                          II must have: Category B1, A2, N2, or B2
                          disease status. Patients in Treatment Group
                          III must have: History of immunological stage
                          3 illness with improvement to stage A1 or N1
                          at entry for at least 3 months prior to study
                          entry.] [AS PER AMENDMENT 5/21/01: Patients
                          in Treatment Group II must have: stage B1,
                          A2, N2, or B2 disease at study entry.].
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8.9 g/dl (if < 2 years of age);
                          > 9.9 g/dl (if >= 2 years of age). Treatment
                          groups only.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 /mm3 Treatment groups
                          only.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x ULN ULN (Upper Limit of
                          Normal). Treatment groups only.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN Treatment groups only.
PATIENT INCLUSION CRIT.   CREATININE: < .9 (if age 12 to 24 months); <
                          1.1 mg/dl (if age 24 to 48 months [AS PER
                          AMENDMENT 7/2/96: if age 2 to 8 years]).
                          Treatment groups only.
PATIENT INCLUSION CRIT.   PRIOR TREATMENT: Required: [AS PER AMENDMENT
                          9/9/99: Treatment Group III: Stable
                          antiretroviral therapy (at least one protease
                          inhibitor plus at least two reverse
                          transcriptase inhibitors) for 3 months prior
                          to study entry.].
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Control
                          Group: Acyclovir for treating varicella.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 12
                          months less than or equal to 08 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Treatment group
                          patients [AS PER AMENDMENT 9/9/99: Treatment
                          Groups I, II, and III] with the following
                          symptoms or conditions are excluded: 1.
                          Active intercurrent infection within the past
                          72 hours. 2. Fever (at least 101 F) within
                          the past 72 hours. 3. History of varicella
                          (chickenpox) or herpes zoster (shingles). 4.
                          Exposure to chickenpox or shingles within the
                          past 4 weeks. 5. HIV-infected, indeterminate,
                          or other immunocompromised household members
                          who have no known history of varicella
                          infection.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Blood products
                          within the past 5 months (or within 5 months
                          prior to a primary varicella episode in the
                          control group patients).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Treatment Group
                          [AS PER AMENDMENT 9/9/99: Treatment Groups I,
                          II, and III]: 1. VZIG or IVIG within 5 months
                          of study entry. [AS PER AMENDMENT 9/9/99:
                          IVIG is prohibited within 12 months of study
                          entry.] 2. Another live vaccine within 30
                          days of any study immunization. 3.
                          Inactivated vaccine within 2 weeks of any
                          study immunization. 4. Systemic steroids
                          within 30 days of study entry. 5. Anti-herpes
                          antiviral drugs (such as acyclovir,
                          famciclovir, valacyclovir, ganciclovir,
                          interferon, or foscarnet) within one week
                          before any study immunization. [AS PER
                          AMENDMENT 9/9/99: Cidofovir is also
                          exlcuded.] Control Group: VZIG or IVIG within
                          5 months prior to study entry or a primary
                          episode of varicella. [AS PER AMENDMENT
                          9/9/99: IVIG is prohibited within 12 months
                          of study entry.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Treatment
                          group [AS PER AMENDMENT 9/9/99: Treatment
                          Groups I, II, and III]: 1. Immunosuppressive
                          therapy. 2. Aspirin. 3. Another live vaccine
                          within 30 days of any study immunization. 4.
                          Inactivated vaccine within 2 weeks of any
                          study immunization. 5. Anti-herpes antiviral
                          drugs (such as acyclovir, famciclovir,
                          valacyclovir, ganciclovir, interferon, or
                          foscarnet) within one week before any study
                          immunization. [AS PER AMENDMENT 9/9/99:
                          Cidofovir is also excluded.] Control Group:
                          Immunosuppressive therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Other
                          known or suspected immune disease. 2. Known
                          hypersensitivity to vaccine components,
                          including neomycin. 3. Other chronic medical
                          or surgical condition or contraindication
                          that would interfere with evaluation.
                          Patients in the treatment group [AS PER
                          AMENDMENT 9/9/99: Treatment Groups I, II, and
                          II] with the following symptoms or conditions
                          will be excluded: 1. Positive VZV antibody.
                          2. Tuberculosis.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0248  Varicella Virus Vaccine
                          (Live)
RESULTS                   AIDS/20711679. Levin M, Gershon A, Weinberg
                          A, Blanchard S, Wells B, Nowak B. Conf
                          Retroviruses Opportunistic Infect. 1999 Jan
                          31-Feb 4;6th:150 (abstract no. 440).
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 0.5 ml containing a
                          minimum of 1350 PFU at Weeks 0 and with
                          possible boost at Week 52
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous
OTHER TREATMENT INFO.     END POINT: Drug safety, immunogenicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Immunologic decline, e.g.,
                          progression to clinical category B or C or a
                          decrease in CD4+ count of at least 50 percent
                          in patients whose CD4+ prior to immunization
                          was greater than 2000 cells/mm3.
OTHER TREATMENT INFO.     MODIFICATION: For Grade 2 or worse hepatic
                          transaminase in patients scheduled to receive
                          vaccine: Hold subsequent doses of vaccine
                          until toxicity resolves to Grade 1.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          991118.
CALIFORNIA                Children's Hosp of Los Angeles/UCLA Med Ctr
                          4650 Sunset Blvd Los Angeles, CA 900276016
                          Zane O'Keefe [phone] Recruiting 991118.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 991118.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 991118.
CALIFORNIA                UCLA Med Ctr / Pediatrics 10833 Le Conte Ave
                          Los Angeles, CA 90095 Maryanne Dillon
                          [phone] Recruiting 001122.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 991118.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 991118.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Maryanne
                          Dillon [phone] Recruiting 000509.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] Recruiting 991118.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 991118.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 991118.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] Recruiting 991118.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Susan Zamer
                          [phone] Recruiting 991118.
FLORIDA                   Sacred Heart Children's Hosp / CMS of Florida
                          5192 Bayou Blvd Pensacola, FL 32503 Susan
                          Wilson [phone] Recruiting 001019.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 000127.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          991118.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 991118.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          991118.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 991118.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000310.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 991118.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 991118.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 991118.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 991118.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Sue Lovelace [phone]
                          Recruiting 991118.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone] No
                          longer recruiting 010702.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 000524.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Lisa Cerrachio
                          [phone] Recruiting 001019.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 991118.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 000419.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Denise Swindell
                          [phone] Recruiting 991118.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 991118.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 991118.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 010731.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 991118.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Shailaja Kancherla Recruiting 000728.
NEW YORK                  Mount Sinai Med Ctr / Pediatrics One Gustave
                          Levy Place / PO Box 1042 New York, NY 10029
                          Eileen Chusid [phone] Recruiting
                          991118.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 991118.
NEW YORK                  New York Hosp - Cornell Med Ctr 505 East 70th
                          St New York, NY 10021 Anne Monroe
                          [phone] Recruiting 001121.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 991118.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 991118.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 991118.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 991118.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          991118.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone]
                          Recruiting 000210.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 991118.

15
UNIQUE IDENTIFIER         NIH/00663
PROTOCOL ID NUMBERS       NIAID ACTG 254
PROTOCOL TITLE            A Randomized, Phase II/III, Double-Blind,
                          Two-Armed Study of Micronized Atovaquone and
                          Azithromycin (AT/AZ) as Compared to
                          Trimethoprim-Sulfamethoxazole (TMP/SMX) in
                          the Prevention of Serious Bacterial
                          Infections When Used in Children Aged 3
                          Months to 19 Years with HIV Infection.
TRIAL CATEGORY            Child
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Wayne M Dankner
PROTOCOL CHAIRS           CO-CHAIR  Ram Yogev
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To determine whether
                          micronized atovaquone/azithromycin
                          combination is as effective as
                          trimethoprim/sulfamethoxazole (TMP/SMX) for
                          prophylaxis against serious bacterial
                          infections in HIV-infected infants and
                          children. To compare long-term safety and
                          tolerance of these two regimens. For the
                          first 30 patients, to examine the likelihood
                          of pharmacokinetic interaction between
                          atovaquone and azithromycin. SECONDARY: To
                          determine Pneumocystis carinii pneumonia
                          (PCP) breakthrough rates, incidence of other
                          opportunistic infections and survival, and
                          hospitalization rates in this patient
                          population.
GENERAL DESCRIPTION       RATIONALE: Although TMP/SMX remains the drug
                          of choice for PCP prophylaxis, drug
                          sensitivity may limit its use. Atovaquone has
                          demonstrated greater safety than TMP/SMX and
                          thus is suitable as a candidate drug for
                          treatment and prophylaxis of PCP.
                          Azithromycin, with a broad anti-microbial
                          spectrum (including mycoplasma and atypical
                          mycoplasma), is an attractive prophylactic
                          agent for use in children with HIV infection,
                          due to its relative safety and once-daily
                          dosing regimen. Therefore, the combination of
                          atovaquone and azithromycin may offer broader
                          antimicrobial coverage and greater safety
                          than TMP/SMX.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either TMP/SMX or combination
                          micronized atovaquone/azithromycin. Crossover
                          to the alternative regimen may occur if
                          serious toxicity is observed. Patients are
                          monitored for occurrence of serious bacterial
                          infections or PCP breakthrough, and when a
                          serious bacterial infection occurs, patients
                          are crossed over to the alternative regimen.
                          Treatment continues until 2 years after the
                          last patient is enrolled. The first 30
                          patients will undergo a pharmacokinetic
                          profile. Patients are followed every 4 weeks
                          for the first 4 months, then every 8 weeks
                          thereafter. [AS PER AMENDMENT 05/28/99: This
                          study was closed to infants and children age
                          19 months and older on 2/15/99; the study is
                          now open to infants age 3 to 18 months (Stage
                          II). Patients who are age 24 months or older
                          at the time of Stage I closure will have
                          end-of-study evaluations and will no longer
                          be followed on protocol. Patients who are
                          less than 24 months of age at the time of
                          Stage I closure will be allowed to continue
                          in the current version of the protocol.
                          Enrollment for children age 3 to 18 months
                          will continue until 50 subjects have been
                          randomized. Because Stage II is an unblinded
                          study, patients who are less than 24 months
                          of age currently enrolled on Version 4.0 will
                          have their study medication regimen unblinded
                          and their atovaquone dose increased.].
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          safety, Drug tolerance, Pharmacokinetics,
                          Drug prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 690 patients. (340
                          patients per treatment arm) [AS PER AMENDMENT
                          3/31/97: Population was changed to 580
                          infants and children, 285 per arm, excluding
                          th
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum 2
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 393/690 001205.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 75
PROTOCOL DETAILS          VERSION NUMBER & DATE: 5 (990528)
PROTOCOL DETAILS          DISEASE STUDIED: Bacterial infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 254
PROTOCOL DETAILS          STUDY DESIGN: Random Allocation; Parallel
                          Designs
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have the following symptoms and conditions:
                          1. Documented laboratory evidence of HIV-1
                          infection. [AS PER AMENDMENT 3/31/97: Infants
                          younger than 18 months must have two positive
                          viral tests (culture, p24, p24 antigen, or
                          ICD p24 antigen) on two different specimens,
                          one of which must be a culture and one of
                          which must have been performed in an
                          ACTG-certified laboratory. Infants 18 months
                          or older must have a positive qualitative or
                          quantitative viral culture from a peripheral
                          blood specimen; a second peripheral blood
                          specimen must be positive by either
                          qualitative culture, DNA-PCR, neutralizable
                          p24 antigen, or ICD p24 assay performed in an
                          ACTG-certified laboratory or two positive
                          tests for HIV antibody (from 2 different
                          peripheral blood specimens) at age 18 months
                          or older.] 2. Risk of developing PCP and
                          requiring prophylaxis according to current
                          MMWR guidelines. [AS PER AMENDMENT 3/31/97:
                          Patients less than 1 year of age must have a
                          CD4 cell count of less than 1,500 cells/mm3
                          or 15% (relative count). Patients between 1
                          and 2 years old must have a CD4 cell count of
                          less than 500 cells/mm3 or 15% (relative
                          count).] 3. No acute or chronic infections
                          that require treatment (including no current
                          suspected or proven active PCP). (Note:
                          Topical antifungal therapy and isoniazid
                          prophylaxis are permitted.) [AS PER AMENDMENT
                          3/31/97: Note: Children with a history of GI
                          intolerance to macrolides may be enrolled.]
                          4. Consent of parent or guardian. Note:
                          Co-enrollment in protocol ACTG 219 is
                          strongly encouraged. [AS PER AMENDMENT
                          3/15/96: Note: Patients co-enrolled in ACTG
                          254 or 245 must have a 4-week waiting period
                          between enrollment into either protocol.].
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 7 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.7 mg/dl (aged two years -
                          adolescent); < 2.5 mg/dl (adolescent). [AS
                          PER ADMENDMENT 3/31/97: < 1.2 (aged 3 months
                          to 2 years).].
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception during the study and for 90
                          days after Not breast-feeding Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: Prior TMP/SMX.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. IVIG. 2.
                          Topical antifungal therapy. 3. Isoniazid
                          prophylaxis. 4. TMP/SMX for secondary PCP
                          prophylaxis.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 03
                          months less than or equal to 18 months.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hypersensitivity to micronized
                          atovaquone and/or azithromycin.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          azithromycin or atovaquone for more than 3
                          consecutive weeks and not within 2 weeks
                          prior to study entry. 2. Rifabutin or
                          clarithromycin within 1 week prior to study
                          entry [AS PER ADMENDMENT 3/31/97: Revised to
                          exclude prophylaxis for disseminated MAC
                          disease prior to entry].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Rifabutin
                          or clarithromycin for Mycobacterium avium
                          complex (MAC) prophylaxis. 2. Antimicrobial
                          treatment lasting more than 28 days for acute
                          infections.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          intolerance to TMP/SMX. 2. Grade 2 or worse
                          diarrhea for more than 1 week or other causes
                          of malabsorption. [3. AS PER AMENDMENT
                          5/28/99: Chronic infection requiring
                          treatment during study period.].
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0084  Atovaquone
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0104  Azithromycin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0030  Trimethoprim
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0031  Sulfamethoxazole
RESULTS                   MED/99278027. Ngo LY, Yogev R, Dankner WM,
                          Hughes WT, Burchett S, Xu J, Sadler B,
                          Unadkat JD. Antimicrob Agents Chemother. 1999
                          Jun;43(6):1516-9.
RESULTS                   AIDS/98929437. Ngo LY, Yogev R, Dankner WM,
                          Hughes WT, Xu J, Unadkat J. Conf Retroviruses
                          Opportunistic Infect. 1998 Feb 1-5;5th:174
                          (abstract no. 506).
RESULTS                   MED/21037891. Dankner WM, Lindsey JC, Levin
                          MJ. Pediatr Infect Dis J 2001 Jan;20(1):40-8.
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 30 mg/kg (or
                          placebo) daily (maximum 1500 mg daily)
                          forminimum of 2 years. [AS PER AMENDMENT
                          3/15/96: Maximum volume 1mL.] [AS PER
                          AMENDMENT 5/28/99: 45 mg/kg daily for
                          subjects < 2months of age at time of
                          unblinding.] Drug 2: 5 mg/kg (or placebo)
                          daily (maximum 250 mg daily) for aminimum of
                          2 years. [AS PER AMENDMENT 3/15/96: Maximum
                          volume 6ml or 1 tablet.] Drug 3: 5 mg/kg
                          Septra (or placebo) daily for a minimum of 2
                          ye[AS PER AMENDMENT 3/15/96: Maximum volume
                          20 ml or 1 double-strtablet or 2
                          single-strength tablets.] Drug 4: 5 mg/kg
                          Septra (or placebo) daily for a minimum of 2
                          ye[AS PER AMENDMENT 3/15/96: Maximum volume
                          20 ml or 1 double-strtablet or 2
                          single-strength tablets.]
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 30 mg/kg (maximum 1500
                          mg). [AS PER AMENDMENT 5/28/99: mg/kg as
                          noted above.] Drug 2: 5 mg/kg (maximum 250
                          mg). Drug 3: 5 mg/kg Septra. Drug 4: 5 mg/kg
                          Septra
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral micronized
                          suspension, 4-oz glass bottles. Drug 2: Oral,
                          40-mg/ml suspension or 250-mg tablets. Drug
                          3: Oral, 40-mg/5 ml suspension or 160-mg DS
                          tablets. Drug 4: Oral, 200-mg/5 ml suspension
                          or 800-mg DS tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 2 years.
OTHER TREATMENT INFO.     END POINT: Primary: Development of serious
                          bacterial infection, toxicity. Secondary:
                          Development of nonserious bacterial
                          infections, PCP breakthrough, survival,
                          pharmacokinetic profile.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Dose-limiting
                          toxicity. 2. Second serious bacterial
                          infection identified after crossover to the
                          alternative regimen. 3. Second occurrence of
                          proven PCP or nonpulmonary pneumocystis
                          following crossover. 4. Study drug
                          discontinuation for more than 28 consecutive
                          days, due to noncompliance or need for
                          treatment of acute bacterial infections
                          (unless approved by study chair).
OTHER TREATMENT INFO.     MODIFICATION: For Grade 3 toxicity: Hold
                          study drug until toxicity resolves to Grade
                          2. For recurrent Grade 3 toxicity, hold study
                          drug until toxicity resolves to Grade 2, then
                          cross over to alternative regimen. If Grade 3
                          toxicity recurs following crossover,
                          discontinue study drugs permanently. If
                          toxicity does not resolve within 28 days at
                          any time, discontinue study drugs
                          permanently. For Grade 4 toxicity (other than
                          anemia that resolves to Grade 2 after a
                          single transfusion): cross over to
                          alternative study regimen.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] No longer
                          recruiting 010227.
ALABAMA                   Univ of South Alabama 1504 Springhill Avenue
                          Mobile, AL 36604 Julie Bebawy [phone]
                          Recruiting 990915.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 950516.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 950227.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] No longer recruiting
                          010501.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 950227.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] No longer recruiting
                          010115.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] No longer recruiting 001213.
CALIFORNIA                Children's Hosp of Los Angeles/UCLA Med Ctr
                          4650 Sunset Blvd Los Angeles, CA 900276016
                          Zane O'Keefe [phone] No longer
                          recruiting 000928.
CALIFORNIA                Cedars Sinai / UCLA Med Ctr 8700 Beverly
                          Boulevard Los Angeles, CA 900481804 Zane
                          O'Keefe [phone] No longer recruiting
                          010115.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          No longer recruiting 990712.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] No longer
                          recruiting 010213.
CONNECTICUT               Univ of Connecticut / Farmington 263
                          Farmington Ave Farmington, CT 06032 Gail
                          Karas [phone] No longer recruiting
                          010123.
CONNECTICUT               Connecticut Children's Med Ctr 263 Farmington
                          Ave Farmington, CT 060303805 Gail Karas
                          [phone] No longer recruiting 010123.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] No longer recruiting
                          960301.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] No longer recruiting 010712.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 950316.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 990915.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 961216.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] No longer
                          recruiting 990805.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 990915.
GEORGIA                   Med College of Georgia 1120 15th St / Dept of
                          Pediatrics / HF 1135 Augusta, GA 30912 Teresa
                          Horne [phone] Recruiting 990915.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 951130.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 950316.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] No longer
                          recruiting 010116.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] Recruiting
                          950404.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          No longer recruiting 010518.
LOUISIANA                 Earl K Long Early Intervention Clinic 1430
                          Tulane Ave TB-8 New Orleans, LA 70112 Kim
                          Anglin [phone] Recruiting 990915.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 950303.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] No longer recruiting
                          000127.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 950524.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 950227.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 950801.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Sue Lovelace [phone] No longer
                          recruiting 000829.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] No longer recruiting 010227.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 970212.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone] No
                          longer recruiting 990712.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 950901.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Silvia Callejas
                          [phone] No longer recruiting 991028.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] No longer recruiting
                          010627.
NEW JERSEY                Cooper Hosp - Univ Med Ctr / UMDNJ - New
                          Jersey Med Schl One Cooper Plaza Camden, NJ
                          08103 Mary Jo Hoyt [phone] No longer
                          recruiting 010627.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          No longer recruiting 990805.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Denise Swindell
                          [phone] Recruiting 950303.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone] No
                          longer recruiting 000228.
NEW YORK                  Cornell Univ Med College 1300 York Ave / PO
                          Box 296 New York, NY 10021 Kathleen O'Keefe
                          [phone] No longer recruiting 990830.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Children's Hosp Pact Prog / Children's Hosp
                          of Buffalo 239 Bryant St Buffalo, NY 14222
                          Debby Phillips [phone] No longer
                          recruiting 960903.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] No longer recruiting 990805.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] No longer recruiting 991006.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 950405.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] No longer recruiting 000228.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          950227.
NEW YORK                  Mount Sinai Med Ctr / Pediatrics One Gustave
                          Levy Place / PO Box 1042 New York, NY 10029
                          Eileen Chusid [phone] No longer
                          recruiting 970424.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] No longer
                          recruiting 010313.
NEW YORK                  Beth Israel Med Ctr / Pediatrics First Ave at
                          16th St New York, NY 10003 Ann Marshak
                          [phone] No longer recruiting 970515.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 950403.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 990915.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] No longer recruiting
                          010612.
NEW YORK                  Montefiore Med Ctr Adolescent AIDS Program
                          111 East 210th St Bronx, NY 10467 Dina Monte
                          [phone] Recruiting 950719.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone] No longer
                          recruiting 010501.
OHIO                      Columbus Children's Hosp 700 Children's Dr
                          Columbus, OH 432052696 Jane Hunkler
                          [phone] Recruiting 990915.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          950717.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone] No
                          longer recruiting 010206.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 950717.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] No longer
                          recruiting 991118.
PENNSYLVANIA              Saint Christopher's Hosp for Children Erie
                          Ave at Front St Philadelphia, PA 191341095
                          Audrey Kamrin [phone] Recruiting
                          951213.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone] No
                          longer recruiting 991209.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          950410.
TENNESSEE                 Vanderbilt Univ Med Ctr 1161 21st Ave South /
                          MCN D-7235 Nashville, TN 372322581 Peggy
                          Bender [phone] Recruiting 970829.
TEXAS                     Hermann Hosp / Univ Texas Health Science Ctr
                          6410 Fannin St / Suite 720 Houston, TX 77030
                          Dr Marilyn Griffiths Doyle [phone] No
                          longer recruiting 960410.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 950324.
VIRGINIA                  Children's Hosp of the King's Daughters 601
                          Children's Lane Norfolk, VA 23507 Donna
                          Sandifer [phone] No longer recruiting
                          010417.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] No longer recruiting 000621.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone] No
                          longer recruiting 000203.

16
UNIQUE IDENTIFIER         NIH/00592
PROTOCOL ID NUMBERS       CC 92 I-125
PROTOCOL TITLE            A Study of Viral Burden in Peripheral Blood
                          Versus Lymphoid Tissue in Human
                          Immunodeficiency Virus Infected Individuals.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
PROTOCOL CHAIRS           CHAIR  SK Stanley
PROTOCOL CHAIRS           CO-CHAIR  AS Fauci
GENERAL DESCRIPTION       PURPOSE: To determine the relative burden of
                          HIV and the relative degree of HIV expression
                          in the peripheral blood mononuclear cells
                          (PBMC) versus the lymph nodes in individual
                          patients with HIV infection. To delineate the
                          precise nature of the perturbations in V-beta
                          subsets of T cells in the peripheral blood
                          versus the lymph nodes of HIV-infected
                          individuals in order to pursue the role of
                          superantigens in the immunopathogenesis of
                          HIV infection. To examine the effect of
                          therapy on viral burden and HIV expression in
                          lymph node versus PBMC. [AS PER AMENDMENT
                          02/94: Enrollment is limited to long-term
                          immunologic nonprogressors.]
GENERAL DESCRIPTION       RATIONALE: Recent studies have demonstrated
                          that there is ten times more virus (per
                          constant number of CD4 T cells) in the lymph
                          nodes than in the PBMC of HIV-infected
                          patients with generalized lymphadenopathy,
                          indicating that the lymph node may be the
                          major reservoir of HIV presence and
                          expression in the body. It is important to
                          establish whether this situation exists in a
                          broad spectrum of HIV patients at various
                          stages of infection from initial acute
                          infection through advanced disease. If
                          patients with early asymptomatic disease are
                          shown to have substantial viral replication
                          in lymph nodes at a time when their
                          peripheral blood reflects a relative latency,
                          this finding will provide a basis for
                          treating patients earlier in the course of
                          their HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients have no more than 400
                          cc of blood drawn during their participation
                          on the study and undergo surgical removal
                          under local anesthesia of a lymph node from
                          the groin, armpit, or neck.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: UNLIMITED patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/UNLIMITED.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (940308)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Longitudinal Study
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: [AS PER AMENDMENT
                          2/94: Patients must have: 1. HIV infection
                          for 7 years or more documented by ELISA and
                          confirmed either by Western blot, positive
                          HIV culture, positive HIV antigen, plasma
                          viremia, or a second antibody test other than
                          ELISA. 2. Long-term immunologic
                          nonprogression [AS PER AMENDMENT 1/14/97: No
                          significant decrease in CD4 cell count since
                          initial diagnosis]. 3. CD4 greater than 500
                          cells/mm3 [AS PER AMENDMENT 1/14/97: CD4
                          count greater than 700 cells/mm3]. 4.
                          Palpable lymph node.].
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 80000 /mm3 [AS PER
                          AMENDMENT 1/14/97].
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 700 cells/mm3 [AS PER
                          AMENDMENT 01/14/97: 700 - 800 - plus.].
PATIENT INCLUSION CRIT.   OTHER: PT and PTT normal.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Prophylaxis
                          for opportunistic infections.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: [AS PER AMENDMENT 1/14/97:
                          Excluded: 1. Alcohol or drug dependency. 2.
                          Any major psychiatric disorders.].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Aspirin within
                          1 week prior to study entry. [2. AS PER
                          AMENDMENT 2/94: Prior antiviral therapy.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: [AS PER AMENDMENT
                          1/14/97: Excluded: Any medications that would
                          interfere with blood clotting (i.e., warfarin
                          or heparin).].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Bleeding diathesis. 2. Need for chronic
                          aspirin therapy. 3. AIDS dementia or
                          AIDS-related malignancy other than minimal
                          Kaposi's sarcoma.
OTHER TREATMENT INFO.     END POINT: Measurements of viral burden.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA accrual 991117.

17
UNIQUE IDENTIFIER         NIH/00554
PROTOCOL ID NUMBERS       NIAID ACTG 219C
PROTOCOL TITLE            Pediatric Late Outcomes Protocol.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Epidemiology
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
PROTOCOL CHAIRS           CHAIR  James Oleske
PROTOCOL CHAIRS           CO-CHAIR  Michael Brady
GENERAL DESCRIPTION       PURPOSE: To describe late outcomes over time
                          in [AS PER AMENDMENT 3/9/00: relation to
                          survival,] growth, neurologic and
                          neuropsychologic function, quality of life,
                          organ system toxicity, metabolic disorders,
                          development of [AS PER AMENDMENT 3/9/00:
                          opportunistic infections and malignancies,
                          and] immunologic and virologic parameters in
                          HIV-infected infants, children, and
                          adolescents. [AS PER AMENDMENT 3/9/00: This
                          will also include evaluation of potential
                          late outcomes, impact of puberty, and
                          complications of antiretroviral and immune
                          therapy received by the patient.] To
                          determine if uninfected infants born to
                          HIV-infected women demonstrate any short- or
                          long-term adverse clinical or laboratory
                          effects [AS PER AMENDMENT 3/9/00: due to
                          exposure to antiretroviral therapy or immune
                          therapy/vaccines in utero, the perinatal
                          period, or early infancy].
GENERAL DESCRIPTION       RATIONALE: The potential long-term benefits,
                          toxicities, and other adverse outcomes of new
                          anti-HIV therapies cannot currently be
                          assessed within the time frame of clinical
                          trials under way. The need exists to better
                          assess both positive and negative late
                          outcomes and late treatment effects in
                          children who are still growing.
GENERAL DESCRIPTION       METHODOLOGY: Children have a complete
                          physical exam, history, Tanner staging,
                          neurologic exam, and growth and
                          quality-of-life assessments every 6 months
                          (if less than 3 years of age) or every 12
                          months (if greater than or equal to 3 years
                          of age). Laboratory tests (such as
                          hematology, chemistries, and urinalysis) are
                          also performed every 6 or 12 months
                          (according to age) in infected individuals
                          and every 6 months or 3 years in uninfected
                          individuals. Audiometry, echocardiograms, and
                          ophthalmic exams are performed at specified
                          intervals. [AS PER AMENDMENT 3/9/00: Clinical
                          Tracking Evaluations will take place
                          according to the following schedules: All
                          patients who are infected: 2, 4, 6 months of
                          age, then every 3 months. All patients who
                          are uninfected: 2, 4, 6, 9, 12, 18, and 24
                          months of age, then every 12 months.]
                          Participants are followed until age 21 [AS
                          PER AMENDMENT 3/9/00: 24] or until lost to
                          follow-up. [AS PER AMENDMENT 3/9/00: PACTG
                          sites that follow patients beyond the age of
                          24 may keep patients on study.].
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Epidemiology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: OPEN patients. 1650
                          uninfected and 2150 infected are projected to
                          be enrolled by June 2002.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until age 21
                          [AS PER AMENDMENT 3/9/00: 24] or lost to
                          follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 5633/OPEN 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 87
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (000309)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: ACTG 219. PACTG 219C
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Longitudinal
                          Study
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: [AS PER AMENDMENT
                          3/9/00: Patients must have: Definitive
                          diagnosis of their HIV status by HIV culture,
                          DNA/RNA PCR, or serology performed as part of
                          their participation in a PACTG clinical trial
                          or by clinical care at a PACTG site.]
                          Patients must meet at least one of the
                          following criteria: 1. Born [AS PER AMENDMENT
                          3/9/00: after January 1, 2000] to an
                          HIV-infected woman who is currently enrolled
                          or has been enrolled in an ACTG perinatal
                          transmission or
                          antiretroviral/immunomodulator therapy
                          protocol [AS PER AMENDMENT 3/9/00: Concurrent
                          and/or prior enrollment in a PACTG protocol
                          is not a requirement.] while pregnant with
                          this child. 2. Indeterminate HIV status and
                          received antiretroviral, immunomodulator, or
                          vaccine therapy in an ACTG treatment
                          protocol. [AS PER AMENDMENT 3/9/00: This
                          criterion has been replaced by the following
                          enrollment criterion: An uninfected child
                          born to an HIV-infected mother prior to
                          January 1, 2000 when the mother was
                          participating in a PACTG or AACTG study while
                          pregnant with the child.] 3. HIV-infected
                          infant, child, or adolescent [AS PER
                          AMENDMENT 3/9/00: born prior to January 1,
                          2000] when the mother was currently or
                          previously enrolled in an ACTG clinical
                          protocol. [AS PER AMENDMENT 3/9/00: Current
                          and/or prior enrollment in a PACTG protocol
                          is not a requirement.] 4. Children and
                          adolescents enrolled in the long-term
                          survivor study. NOTE: Children and
                          adolescents enrolled solely in ACTG 220
                          (pre-enrollment protocol) or other
                          observational studies are not eligible for
                          this protocol until they become enrolled in
                          an ACTG treatment trial (adult, perinatal, or
                          pediatric). [AS PER AMENDMENT 3/9/00: This
                          criterion and note have been removed.].
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 01 days
                          less than or equal to 24 years.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: [AS PER AMENDMENT 3/9/00:
                          Excluded: Perinatally exposed and
                          HIV-infected infants, children, and
                          adolescents who are unable to adhere to study
                          visit schedule.].
RESULTS                   MED/99114156. Culnane M, Fowler M, Lee SS,
                          McSherry G, Brady M, O'Donnell K, Mofenson L,
                          Gortmaker SL, Shapiro DE, Scott G, Jimenez E,
                          Moore EC, Diaz C, Flynn PM, Cunningham B,
                          Oleske J. JAMA. 1999 Jan 13;281(2):151-7.
RESULTS                   ICA11/96923299. Brady MT, Clark C, Weedy C,
                          Fowler M, Mofenson L, Oleske J. Int Conf
                          AIDS. 1996 Jul 7-12;11(2):43 (abstract no.
                          We.D.131)M
RESULTS                   Moye J, Cervia J, Lindsey JC, Hughes MD,
                          Seage G, Dankner W, Oleske J. 8th Conf Retro
                          and Opportun Infect. 2001 Feb 4-8 (abstract
                          no. 515).
OTHER TREATMENT INFO.     END POINT: Late patient outcomes, including
                          survival, growth, nutrition, quality of life,
                          neurologic and neuropsychologic parameters,
                          organ system toxicities, AIDS-defining
                          opportunistic infections or cancer, and
                          immunologic and virologic parameters.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          990826.
ALABAMA                   Univ of South Alabama 1504 Springhill Avenue
                          Mobile, AL 36604 Julie Bebawy [phone]
                          Recruiting 990826.
ARIZONA                   Phoenix Childrens Hosp 909 East Brill Street
                          Phoenix, AZ 85006 Laura Clarke-Steffan
                          [phone] Recruiting 001024.
CALIFORNIA                UCLA Med Ctr 10833 Le Conte Ave Los Angeles,
                          CA 90095 Maryanne Dillon [phone]
                          Recruiting 001024.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 930709.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 930824.
CALIFORNIA                San Francisco Gen Hosp 1001 Potrero Ave /
                          Ward 6 / D-4 San Francisco, CA 94110 Maureen
                          Shannon [phone] Recruiting 930824.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 930616.
CALIFORNIA                UCLA Med Ctr / Pediatrics 10833 Le Conte Ave
                          Los Angeles, CA 90095 Maryanne Dillon
                          [phone] No longer recruiting 010702.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Maryanne
                          Dillon [phone] Recruiting 930609.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] Recruiting 930408.
CALIFORNIA                Children's Hosp of Los Angeles/UCLA Med Ctr
                          4650 Sunset Blvd Los Angeles, CA 900276016
                          Zane O'Keefe [phone] Recruiting 940627.
CALIFORNIA                Cedars Sinai / UCLA Med Ctr 8700 Beverly
                          Boulevard Los Angeles, CA 900481804 Zane
                          O'Keefe [phone] Recruiting 930802.
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 001024.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 930430.
CONNECTICUT               Univ of Connecticut / Farmington 263
                          Farmington Ave Farmington, CT 06032 Gail
                          Karas [phone] No longer recruiting
                          010130.
CONNECTICUT               Connecticut Children's Med Ctr 263 Farmington
                          Ave Farmington, CT 060303805 Gail Karas
                          [phone] Recruiting 990826.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] No longer recruiting
                          960301.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Julie Ziegler
                          [phone] Recruiting 001024.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 930729.
FLORIDA                   Sacred Heart Children's Hosp / CMS of Florida
                          5192 Bayou Blvd Pensacola, FL 32503 Susan
                          Wilson [phone] Recruiting 001019.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 930514.
FLORIDA                   Univ of Miami / Jackson Memorial Hosp 1500
                          Northwest 12th Ave / 8th Floor Miami, FL
                          33136 Patricia Bryan [phone] Recruiting
                          001024.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 970317.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 961216.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          950201.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 990826.
GEORGIA                   The Med Ctr Inc 710 Center St Columbus, GA
                          31901 Dawn Barnes [phone] Recruiting
                          990826.
GEORGIA                   Med College of Georgia 1120 15th St / Dept of
                          Pediatrics / HF 1135 Augusta, GA 30912 Teresa
                          Horne [phone] Recruiting 990826.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 930430.
ILLINOIS                  Mt Sinai Hosp Med Ctr / Dept of Pediatrics
                          Women's and Children's HIV Program / 15th
                          Street and CaliforniaChicago, IL 60608 Brenda
                          Wolfe [phone] Recruiting 001025.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 930520.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          940718.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] Recruiting
                          930910.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 990826.
LOUISIANA                 Univ Hosp 2021 Perdido St New Orleans, LA
                          70112 Kim Anglin [phone] Recruiting
                          001025.
LOUISIANA                 Earl K Long Early Intervention Clinic 1430
                          Tulane Ave TB-8 New Orleans, LA 70112 Kim
                          Anglin [phone] Recruiting 990826.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 930831.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Bishop [phone] Recruiting 930802.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 940304.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 931213.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 930609.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Sue Lovelace [phone]
                          Recruiting 940124.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 931118.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 970224.
NORTH CAROLINA            Univ of North Carolina at Chapel Hill / Duke
                          Univ Med Ctr PO Box 3499 Durham, NC 27710
                          John Swetnam [phone] Recruiting 990826.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 930708.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 940304.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Lisa Cerrachio
                          [phone] Recruiting 940610.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 931227.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 930412.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 940815.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 930830.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Shailaja Kancherla Recruiting 931022.
NEW YORK                  Mount Sinai Med Ctr / Pediatrics One Gustave
                          Levy Place / PO Box 1042 New York, NY 10029
                          Eileen Chusid [phone] Recruiting
                          990623.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 930601.
NEW YORK                  Beth Israel Med Ctr / Pediatrics First Ave at
                          16th St New York, NY 10003 Ann Marshak
                          [phone] No longer recruiting 970514.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 931013.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 990826.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 990826.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 930824.
NEW YORK                  Montefiore Med Ctr Adolescent AIDS Program
                          111 East 210th St Bronx, NY 10467 Dina Monte
                          [phone] Recruiting 990826.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 940405.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 931215.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Denise Swindell
                          [phone] Recruiting 930402.
NEW YORK                  Cornell Univ Med College 1300 York Ave / PO
                          Box 296 New York, NY 10021 Kathleen O'Keefe
                          [phone] Recruiting 940114.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 930830.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] Recruiting 930729.
NEW YORK                  Montefiore Medical / AECOM 1300 Morris Park
                          Ave Bronx, NY 19461 Gayle Kreinik
                          [phone] Recruiting 010731.
NEW YORK                  New York Hosp - Cornell Med Ctr 505 East 70th
                          St New York, NY 10021 Anne Monroe
                          [phone] Recruiting 001005.
OHIO                      Columbus Children's Hosp 700 Children's Dr
                          Columbus, OH 432052696 Jane Hunkler
                          [phone] Recruiting 990826.
OREGON                    Oregon Health Sciences Univ 3181 Southwest
                          Sam Jackson Park Rd Portland, OR 97201 Toni
                          Kempner [phone] Recruiting 010529.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          930514.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 930611.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 930402.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          931206.
PENNSYLVANIA              Saint Christopher's Hosp for Children Erie
                          Ave at Front St Philadelphia, PA 191341095
                          Audrey Kamrin [phone] Recruiting
                          931216.
RHODE ISLAND              Rhode Island Hosp / Brown Univ 593 Eddy St
                          Providence, RI 02903 Carolyn Dwyer
                          [phone] No longer recruiting 960408.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Genny Connelly [phone]
                          Recruiting 930520.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          930802.
TENNESSEE                 Vanderbilt Univ Med Ctr 1161 21st Ave South /
                          MCN D-7235 Nashville, TN 372322581 Peggy
                          Bender [phone] Recruiting 000403.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 940706.
TEXAS                     Children's Med Ctr of Dallas 1935 Motor St
                          Dallas, TX 75235 Paula Luallen [phone]
                          Recruiting 001024.
VIRGINIA                  Children's Hosp of the King's Daughters 601
                          Children's Lane Norfolk, VA 23507 Donna
                          Sandifer [phone] Recruiting 960426.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 970320.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 931206.

18
UNIQUE IDENTIFIER         NIH/01406
PROTOCOL ID NUMBERS       NIAID HIVNET 024
PROTOCOL TITLE            Phase III Trial of Antibiotics to Reduce
                          Chorioamnionitis-Related Perinatal HIV
                          Transmission.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Pregnancy
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine if low-cost antibiotic
                          treatment given twice during pregnancy aimed
                          at reducing chronic and acute
                          chorioamnionitis will reduce perinatal HIV
                          transmission.
GENERAL DESCRIPTION       RATIONALE: Obstetric risk factors for HIV
                          maternal-child transmission (MCT) include
                          preterm birth, prolonged rupture of the
                          membranes, and chorioamnionitis. Many preterm
                          births are associated with and likely caused
                          by chorioamnionitis. The relationship between
                          bacterial vaginosis, preterm birth,
                          histologic chorioamnionitis and perinatal
                          transmission of HIV has been consistently
                          demonstrated. Perinatal HIV transmission is
                          more common in preterm infants, and there is
                          now evidence that sub-clinical
                          chorioamnionitis is a substantial risk factor
                          for MCT. For this study, the primary
                          hypothesis is that early and appropriate
                          treatment of sub-clinical chorioamnionitis
                          prior to the onset of spontaneous preterm
                          labor, and/or antibiotic treatment during
                          labor to prevent premature rupture of
                          membrane-associated-chorioamnionitis will
                          reduce the risk of perinatal HIV
                          transmission.
GENERAL DESCRIPTION       METHODOLOGY: At 20 to 24 weeks, women
                          randomized to receive antibiotics receive
                          metronidazole and erythromycin for 7 days.
                          Women randomized to the control group receive
                          identically appearing placebos. With the
                          onset of contractions and/or premature
                          rupture of membranes, study participants will
                          initiate a second oral course of antibiotics
                          consisting of metronidazole and ampicillin or
                          placebo every 4 hours, continuing after
                          delivery until the course is completed. All
                          HIV-infected women and their neonates will be
                          offered the HIVNET 012 nevirapine (NVP)
                          regimen. If the mother accepts the NVP for
                          herself and her baby, she will be given 1
                          dose of NVP to be taken at onset of labor,
                          and her baby will receive 1 dose of NVP at 72
                          hours post-birth or discharge, whichever
                          occurs earlier. If the mother refuses NVP or
                          is uninfected, she will receive a matched
                          placebo at the 26 to 30 week visit to
                          preserve participant confidentiality. This
                          study takes place in Blantyre and Lilongwe,
                          Malawi, in Lusaka, Zambia, and in Dar es
                          Salaam, Tanzania.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010716)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug
                          prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 3720 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/3720.
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (010417)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants must
                          be: 1. HIV positive at enrollment. 2. 20 to
                          24 weeks gestation. 3. Willing to take
                          antibiotic treatment as scheduled. 4.
                          Planning to deliver at 1 of the study sites.
                          5. Willing to come back for follow-up visits
                          for 1 year post-partum.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Any
                          medication deemed medically necessary for
                          either the mother or neonate.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Participants with
                          the following prior conditions are excluded:
                          1. Allergy to penicillin, ampicillin,
                          erythromycin, or metronidazole. 2. Known
                          major illnesses likely to influence pregnancy
                          outcome including diabetes, severe renal or
                          heart disease, or active tuberculosis, prior
                          to randomization. 3. Known major obstetric
                          problems such as placenta previa, ruptured
                          membranes or multiple pregnancy prior to
                          randomization. 4. Known central nervous
                          system diseases, including seizures.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Alcohol use during
                          the trial.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antibiotics,
                          other than treatment for syphilis or
                          gonorrhea, within the last 2 weeks. 2.
                          Anticoagulant drugs.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0116  Nevirapine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: All HIV-infected
                          women: 200 mg at onset of labor. Neonates: 2
                          mg/kg (suspension), 1 dose
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     END POINT: Infant HIV infection as determined
                          by a positive RNA PCR on dried blood spots on
                          filter paper taken at 4 to 6 weeks. Composite
                          of infant HIV infection and mortality at 1
                          year of age.
OTHER TREATMENT INFO.     DISCONTINUE: Participants may be discontinued
                          from treatment for the following reasons: 1.
                          Participant refuses further treatment and/or
                          follow-up evaluations. 2. Investigator
                          determines that further participation would
                          be detrimental to the participant's health or
                          well-being. 3. Participant experiences a
                          severe allergic reaction to the study drugs.
SUPPORTING AGENCY         Natl Institute of Child Health and Human
                          Development.
LAST REVISION DATE        20010716

19
UNIQUE IDENTIFIER         FDA/01404
PROTOCOL ID NUMBERS       FDA 245F
PROTOCOL TITLE            An Open Label, Phase II Study of
                          Amprenavir/Ritonavir, Saquinavir/Ritonavir or
                          Efavirenz in HIV-Infected Subjects Following
                          Failure with Kaletra (ABT-378/Ritonavir) as
                          Their First Protease Inhibitor Based HAART.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To study amprenavir/ritonavir,
                          saquinavir/ritonavir or efavirenz in
                          HIV-infected patients following failure with
                          Kaletra (ABT-378/ritonavir) as their first
                          protease inhibitor based HAART. Methodology:
                          This is a 3-arm study in the salvage of
                          Kaletra failures.
GENERAL DESCRIPTION       METHODOLOGY: This is a 3-arm study in the
                          salvage of Kaletra failures.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010618)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/24.
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: M01-287
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have (within 30 days prior to the initial
                          dosing): 1. Two most recent viral loads of at
                          least 1,000 copies/ml obtained after at least
                          24 weeks of ABT-378/r therapy, and while
                          still on ABT-378/r; or, initial suppression
                          with ABT-378/r (to less than 400 copies/ml)
                          followed by rebound while still on ABT-378/r
                          therapy. Rebound is defined as having a viral
                          load of at least 1,000 copies/ml on the 2
                          most recent viral loads, obtained at least 1
                          week apart. 2. A viral isolate which
                          demonstrates reduced susceptibility to
                          ABT-378 as defined as: Study patients whose
                          genotype contains at least 1 primary protease
                          mutation plus at least 2 other mutations
                          (primary or secondary) will have phenotypic
                          analysis performed. Patients whose viral
                          isolate displays greater than 10-fold reduced
                          susceptibility to ABT-378 compared to wild
                          type virus meet entry criteria. 3. Vital
                          signs, physical examination and laboratory
                          results which do not exhibit evidence of
                          acute illness. 4. Screening viral isolate
                          which meets criteria for selection of 1 of
                          the salvage regimens.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl Within the previous 3
                          months.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 20000 /microL Within the
                          previous 3 months.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN Within the previous 3
                          months.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN Within the previous 3
                          months.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN ULN (Upper Limit of
                          Normal). Within the previous 3 months.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70 Within the previous 3
                          months.
PATIENT INCLUSION CRIT.   OTHER: Triglyceride: < 750 mg/dl (fasting).
                          Within the previous 3 months.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Current
                          antiretroviral therapy during screening until
                          a new regimen is initiated.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic pancreatitis. 2.
                          Screened for participation in this study
                          within the past 12 weeks.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Treatment for
                          an active opportunistic infection within 30
                          days of screening. 2. Any protease inhibitor
                          other than ABT-378/r for more than 2 weeks.
                          3. Medications that are contraindicated with
                          either of the patient's assigned regimens
                          within 30 days prior to the initial dosing.
                          4. Any medication, including over-the-counter
                          medicine, herbal medicines, alcohol, or
                          recreational drugs, within 30 days prior to
                          the initial dosing, without the knowledge and
                          permission of the principal investigator.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Medications that are contraindicated with
                          either of the patient's assigned regimens. 2.
                          Systemic chemotherapy. 3. Any medication,
                          including over-the-counter medicine, herbal
                          medicines, alcohol, or recreational drugs,
                          without the knowledge and permission of the
                          principal investigator.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Patients, that in
                          the opinion of the principal investigator,
                          are unlikely to comply with the study
                          protocol or are unsuitable for any other
                          reason. 2. Patients with any condition that,
                          in the opinion of the principal investigator,
                          may obscure the proper observation of the
                          safety or activity of the treatment regimens
                          in the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0244  Ritonavir
SUPPORTING AGENCY         Abbott Laboratories.
LAST REVISION DATE        20010618

20
UNIQUE IDENTIFIER         FDA/01403
PROTOCOL ID NUMBERS       FDA 295D
PROTOCOL TITLE            A Phase III Open-Label, Randomized,
                          Active-Controlled Study Assessing the
                          Efficacy and Safety of T-20 (HIV-1 Fusion
                          Inhibitor) in Combination with an Optimized
                          Background Regimen, Versus Optimized
                          Background Regimen Alone, in Patients with
                          Prior Experience and/or Prior Documented
                          Resistance to Each of the Three Classes of
                          Approved Antiretrovirals (
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To demonstrate that a deliverable
                          dose of 90 mg bid of T-20 (corresponding to
                          the 100 mg nominal dose studies in Phase
                          I/II) added to an optimized background (OB)
                          regimen provides an additional drop in plasma
                          HIV-1 RNA of at least 0.5 log10 copies/ml
                          compared to the OB regimen alone at Week 24,
                          as measured by the difference between the 2
                          treatment arms in the mean changes from
                          baseline in plasma HIV-1 RNA at Week 24. To
                          demonstrate the durability of efficacy of
                          T-20 plus OB regimen, as measured by the
                          percentage of patients who responded with
                          viral load as follows: a) less than 50
                          copies/ml; b) 50-400 copies/ml, c) at least a
                          1 log10 decrease from baseline but greater
                          than 400 copies/ml; and d) virological
                          failure at Week 24; and maintain response in
                          each category or better at Week 48.
                          Methodology: An OB regimen is selected to be
                          initiated at baseline by the physician and
                          patient. The OB regimen is based on the
                          patient's prior treatment history as well as
                          the results from the first screening visit
                          HIV-1 genotypic and phenotypic (GT and PT)
                          resistance testing and prior GT/PT
                          antiretroviral resistance testing (if
                          available). Prior or current laboratory
                          abnormalities, including triglycerides and
                          cholesterol, should also be taken into
                          account when selecting the OB regimen.
                          Patients are stratified with respect to the
                          following: 1) screening viral load (less than
                          40,000 or 40,000 or more copies/ml); and 2)
                          number of allowed investigational
                          antiretrovirals (0, 1, or 2). Patients then
                          are randomized to receive 1 of the following
                          treatments for 48 weeks: OB regimen or OB
                          plus T-20 regimen. Patients are seen for
                          evaluation of efficacy and safety at Weeks 1,
                          2, and 4, every 4 weeks through Week 24, and
                          then every 8 weeks through Week 48. In
                          addition, efficacy only is evaluated at Weeks
                          6, 10, and 14. Patients also may be seen at
                          additional visits during the study for plasma
                          HIV-1 RNA measurements to potentially confirm
                          virological failure. Patients initially
                          randomized to the OB arm who meet the
                          criteria for virological failure and who
                          switch to OB plus T-20 after Week 8 are
                          followed under a new (switch) schedule of
                          assessments. Patients are encouraged to
                          change their OB regimen at the time of
                          switch. Patients initially randomized to the
                          OB plus T-20 arm who meet the criteria for
                          virological failure may continue to receive
                          OB plus T-20 if the patient and the physician
                          feel that there is sufficient benefit.
                          Patients are encouraged to change their OB
                          regimen after Week 8 if they choose to
                          continue on OB plus T-20 despite meeting the
                          criteria for virological failure. Patients on
                          OB or OB plus T-20 arm who meet the criteria
                          for virological failure but who do not wish
                          to either switch to T-20 (for patients
                          initially randomized to OB arm) or continue
                          with T-20 (for patients initially randomized
                          to OB plus T-20) are allowed to remain in the
                          study for a maximum of 1 month. At the end of
                          the 48 weeks of treatment, patients are
                          allowed to participate in 1 of the following
                          treatment extensions: a) roll-over and
                          receive OB plus T-20 (for patients receiving
                          OB alone); or b) continue taking OB plus T-20
                          (for patients already receiving OB plus
                          T-20), for a maximum of an additional 48
                          weeks (plus 4 weeks safety follow-up period),
                          or until 12 weeks after commercial
                          availability of T-20 in the country in which
                          they are treated, whichever comes first. All
                          patients are followed for a maximum of 100
                          weeks from their initial baseline visit date.
GENERAL DESCRIPTION       METHODOLOGY: An OB regimen is selected to be
                          initiated at baseline by the physician and
                          patient. The OB regimen is based on the
                          patient's prior treatment history as well as
                          the results from the first screening visit
                          HIV-1 genotypic and phenotypic (GT and PT)
                          resistance testing and prior GT/PT
                          antiretroviral resistance testing (if
                          available). Prior or current laboratory
                          abnormalities, including triglycerides and
                          cholesterol, should also be taken into
                          account when selecting the OB regimen.
                          Patients are stratified with respect to the
                          following: 1) screening viral load (less than
                          40,000 or 40,000 or more copies/ml); and 2)
                          number of allowed investigational
                          antiretrovirals (0, 1, or 2). Patients then
                          are randomized to receive 1 of the following
                          treatments for 48 weeks: OB regimen or OB
                          plus T-20 regimen. Patients are seen for
                          evaluation of efficacy and safety at Weeks 1,
                          2, and 4, every 4 weeks through Week 24, and
                          then every 8 weeks through Week 48. In
                          addition, efficacy only is evaluated at Weeks
                          6, 10, and 14. Patients also may be seen at
                          additional visits during the study for plasma
                          HIV-1 RNA measurements to potentially confirm
                          virological failure. Patients initially
                          randomized to the OB arm who meet the
                          criteria for virological failure and who
                          switch to OB plus T-20 after Week 8 are
                          followed under a new (switch) schedule of
                          assessments. Patients are encouraged to
                          change their OB regimen at the time of
                          switch. Patients initially randomized to the
                          OB plus T-20 arm who meet the criteria for
                          virological failure may continue to receive
                          OB plus T-20 if the patient and the physician
                          feel that there is sufficient benefit.
                          Patients are encouraged to change their OB
                          regimen after Week 8 if they choose to
                          continue on OB plus T-20 despite meeting the
                          criteria for virological failure. Patients on
                          OB or OB plus T-20 arm who meet the criteria
                          for virological failure but who do not wish
                          to either switch to T-20 (for patients
                          initially randomized to OB arm) or continue
                          with T-20 (for patients initially randomized
                          to OB plus T-20) are allowed to remain in the
                          study for a maximum of 1 month. At the end of
                          the 48 weeks of treatment, patients are
                          allowed to participate in 1 of the following
                          treatment extensions: a) roll-over and
                          receive OB plus T-20 (for patients receiving
                          OB alone); or b) continue taking OB plus T-20
                          (for patients already receiving OB plus
                          T-20), for a maximum of an additional 48
                          weeks (plus 4 weeks safety follow-up period),
                          or until 12 weeks after commercial
                          availability of T-20 in the country in which
                          they are treated, whichever comes first. All
                          patients are followed for a maximum of 100
                          weeks from their initial baseline visit date.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010717)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 525 patients. Patients
                          will be randomized at a ratio of 1:2 for
                          OB:OB + T-20 treatment.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 58 weeks (6
                          weeks of screening, 48 weeks of treatment,
                          and 4 weeks of follow-up). An optional
                          treatment extension will allow patients to be
                          followed for a maximum of 100 weeks from
                          their initial baseline visit date.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/525.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 22
PROTOCOL DETAILS          VERSION NUMBER & DATE: (010330)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: T20-302
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Parallel Designs;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV infection. 2. Have HIV-1 RNA of at
                          least 5,000 copies/ml.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Prior experience
                          (for at least 3 months) and/or prior
                          documented resistance to at least 1 member of
                          each of the 3 classes of approved
                          antiretrovirals (nucleoside reverse
                          transcriptase inhibitors [NRTIs],
                          nonnucleoside reverse transcriptase
                          inhibitors [NNRTIs], and protease inhibitors
                          [PIs]). If a patient has prior documented
                          treatment-limiting toxicity to NNRTIs, such
                          that she/he is unable to use any agents in
                          that class, 3 months prior experience or
                          viral resistance to that agent or class may
                          not be required if written permission from
                          Roche has been obtained.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 16
                          years less than or equal to N/A.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0306  T-20
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: OB plus T-20 arm: 90
                          mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: OB plus T-20 arm: 180
                          mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous injection
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks. There is an
                          optional treatment extension of 48 weeks, or
                          until 12 weeks after commercial availability
                          of T-20 in the country where patients are
                          treated, whichever comes first.
OTHER TREATMENT INFO.     END POINT: Efficacy; safety; tolerability;
                          other parameters;
                          pharmacokinetics/pharmacodynamics; and
                          quality of life/pharmacoeconomics.
SUPPORTING AGENCY         Hoffmann - La Roche Inc.
LAST REVISION DATE        20010717
OTHER                     Prahran Market Clinic 131 Commercial Rd South
                          Yarra, Helen Wood (613)982-64500 Recruiting
                          010716.
OTHER                     CHU Saint Pierre Rue Haute 322 Brussels,
                          Nathan Clumeck (02 )535- 41 31 Recruiting
                          010716.
OTHER                     Alfred Hosp Commercial Rd Prahan, Janine
                          Roney (613)927-66908 Recruiting 010716.
OTHER                     Royal Free Hosp Pond Street London, Margaret
                          Johnson (020)783-02589 Recruiting 010716.
OTHER                     Western Gen Hosp Regional Infectious Diseases
                          Unit / Crewe Rd Edinburgh, Sheila Morris
                          (013)153-72842 Recruiting 010716.
OTHER                     Univ College London Med School Mortimer
                          Market Centre London, David Cornforth
                          (004)420-73809810 Recruiting 010716.
OTHER                     Saint Vincent's Hosp 376 Victoria Steet / 2nd
                          Floor Darlinghurst, John Miller
                          (612)838-22994 Recruiting 010716.
OTHER                     Taylors Square Clinic 302 Bourke St Taylor
                          Square Sydney, Neil Bodsworth (612)933-16147
                          Recruiting 010716.
OTHER                     UZ Gasthuisberg Afdoling IG Algernene /
                          Herestraat 49 Leuven , Eric Van Wijngaerden
                          (016) 34- 42 75 Recruiting 010716.
OTHER                     North Manchester Gen Hosp Dept of Infectious
                          Diseases Research / Delauneys Rd Crumpsall
                          Manchester, Rob Daintith (016)172-02615
                          Recruiting 010716.
OTHER                     Inst of Tropical Medicine Dept of Clinical
                          Sciences / Nationalestraat 155 Antwerpe,
                          Danni Van den Branden [phone]
                          Recruiting 010716.
OTHER                     Royal Liverpool Univ Hosp Prescott St
                          Liverpool, Dr Peter Carey (015)170-62629
                          Recruiting 010716.
OTHER                     Hopital cantonal / Div des maladies
                          infectieuses CH-1211 Geneve, Bernard Hirschel
                          (412)237-29812 Recruiting 010716.
OTHER                     Univ Hosp Basel / Med Outpatient Dept
                          Petersgraben 4 4031 Basel, Manuel Battegay
                          (416)126-55072 Recruiting 010716.
OTHER                     CHUV 1101 Lausanne, Serge Gallant
                          (412)131-41022 Recruiting 010716.
OTHER                     Holdsworth House General Practice Suite 1 32A
                          Holdsworth House Darlinghurst, Anthony Frater
                          (612)933-17228 Recruiting 010716.
OTHER                     King's College Hospital Department of HIV /
                          Cutcombe Road London, Dee Graham
                          (020)734-63479 Recruiting 010716.
OTHER                     Carlton Clinic 88 Rathdowne St Carlton,
                          Jonathan Anderson (613)934-79422 Recruiting
                          010716.
OTHER                     Brighton Gen Hosp Elm Grove Brighton, Martin
                          Fisher [phone] Recruiting 010716.
OTHER                     Royal Brisbane Hosp Infectious Disease Ward /
                          Wattlebrae Herston Rd Herston, Anthony
                          Allworth (617)363-68761 Recruiting 010716.
OTHER                     Universitatsspital Zurich Ramistrasse 100
                          Zurich, Markus Flepp (41 )125-5 3222
                          Recruiting 010716.
OTHER                     Chelsea and Westminster Hosp St Stephens
                          Centre / 369 Fulham Road London, Mark Nelson
                          (020)874-65610 Recruiting 010716.

21
UNIQUE IDENTIFIER         FDA/01401
PROTOCOL ID NUMBERS       FDA 298D
PROTOCOL TITLE            An Open-Label Study of a Once Daily Dose of
                          Emtricitabine in Combination with Other
                          Antiretroviral Agents in HIV-Infected
                          Pediatric Patients.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To obtain long-term safety
                          experience for antiretroviral regimens
                          containing emtricitabine in HIV-1 infected
                          pediatric patients. To determine the
                          steady-state emtricitabine concentrations in
                          HIV-1 infected pediatric patients and, if
                          necessary, to refine the dose of
                          emtricitabine to achieve plasma
                          concentrations comparable to those in adults
                          given 200 mg emtricitabine once daily. To
                          obtain antiretroviral activity data for
                          antiretroviral regimens containing
                          emtricitabine in pediatric patients.
                          Methodology: Children are placed into 1 of 4
                          treatment groups based on age: Group 1, 3
                          months to 24 months; Group 2, 25 months to 6
                          years; Group 3, 7 years to 12 years; Group 4,
                          13 years to 17 years. They receive baseline
                          evaluations. Antiretroviral-naive patients
                          receive emtricitabine plus stavudine plus
                          lopinavir/ritonavir.
                          Antiretroviral-experienced patients replace
                          lamivudine with emtricitabine. Patients
                          return to the clinic for follow-up visits at
                          Weeks 2 and 4 and then every 4 weeks until
                          Week 48. Safety is evaluated using adverse
                          events, which are reviewed at every clinic
                          visit. Clinical laboratory data and
                          full-profile pharmacokinetics of
                          emtricitabine are evaluated at some visits.
                          After the Week 48 study evaluations are
                          completed, individual patients may continue
                          to receive study medication (as provided by
                          the sponsor) until commercially available, if
                          certain criteria are met.
GENERAL DESCRIPTION       METHODOLOGY: Children are placed into 1 of 4
                          treatment groups based on age: Group 1, 3
                          months to 24 months; Group 2, 25 months to 6
                          years; Group 3, 7 years to 12 years; Group 4,
                          13 years to 17 years. They receive baseline
                          evaluations. Antiretroviral-naive patients
                          receive emtricitabine plus stavudine plus
                          lopinavir/ritonavir.
                          Antiretroviral-experienced patients replace
                          lamivudine with emtricitabine. Patients
                          return to the clinic for follow-up visits at
                          Weeks 2 and 4 and then every 4 weeks until
                          Week 48. Safety is evaluated using adverse
                          events, which are reviewed at every clinic
                          visit. Clinical laboratory data and
                          full-profile pharmacokinetics of
                          emtricitabine are evaluated at some visits.
                          After the Week 48 study evaluations are
                          completed, individual patients may continue
                          to receive study medication (as provided by
                          the sponsor) until commercially available, if
                          certain criteria are met.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010613)
PROTOCOL DETAILS          STUDY INTENT: Combination and single
                          pharmacokinetics, Drug safety,
                          Pharmacodynamics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 to 100 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/60 to 100.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 12
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: FTC-203
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Nonrandomized Concurrent Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented evidence of an HIV-1
                          infection prior to the initiation of
                          screening tests/procedures. 2. Plasma HIV-1
                          RNA load from 5,000 to 500,000 copies/ml
                          (plus or minus 20%) at screening if
                          antiretroviral-naive. 3. Plasma HIV-1 RNA
                          level of no more than 400 copies/ml at
                          screening if antiretroviral-experienced. 4.
                          Absolute CD4+ cell count of greater than 200
                          cells/mm3. 5. Willingness to use an effective
                          method of contraception while enrolled in the
                          study and for a period of at least 1 month
                          after the last dose of emtricitabine if
                          sexually active and/or of childbearing
                          potential (male and female). 6. Age of 3
                          months (i.e., 90 days) to 17 years of age,
                          inclusive. Age will be determined at the
                          baseline time point. 7. Consent of parent or
                          guardian.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 200 cells/mm3.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 30 days after Not pregnant Negative
                          pregnancy test.
PATIENT INCLUSION CRIT.   WEIGHT: More than 2.5 kg (5.5 lb) and, if a
                          neonate, at least 38 weeks of gestation.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required for
                          antiretroviral-experienced patients: Stable
                          antiretroviral regimen containing lamivudine
                          for at least 3 months (i.e., at least 90
                          days).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 03
                          months less than or equal to 17 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Malabsorption or severe chronic diarrhea
                          (Grade 2 or greater) within 30 days before
                          entry. 2. An acute and serious medical event
                          within 30 days of screening. Acute treatment
                          must have been completed for 14 days prior to
                          study entry. 3. An AIDS defining
                          opportunistic infection within 12 months of
                          screening. 4. A history of acute or chronic
                          pancreatitis.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy, with the exception of no more than
                          56 days perinatal prophylaxis, for
                          antiretroviral-naive patients. 2. Any
                          investigational drug, agent, and/or vaccine
                          (with the exception of emivirine and
                          investigational formulations of approved
                          drugs) within the 30 days prior to baseline.
                          3. Acute treatment, within 14 days prior to
                          study entry, for an acute and serious medical
                          event.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Treatment
                          for active tuberculosis. Excluded for
                          antiretroviral-naive patients:
                          Immunomodulators (with the exception of
                          immune globulin), investigational
                          drug/agents/vaccines (with the exception of
                          investigational formulations of approved
                          drugs), lovastatin, simvastatin, flecainide,
                          propafenone, astemizole, terfenadine,
                          midazolam, triazolam, cisapride, pimozide,
                          ergotamine, ergonovine, methylergonovine,
                          dihydroergotamine, rifampin, and St. John's
                          wort. Excluded for antiretroviral-experienced
                          patients: Immunomodulators (with the
                          exception of immune globulin) and/or
                          investigational drug/agents/vaccines (with
                          the exception of emivirine and
                          investigational formulations of approved
                          drugs).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Inability to
                          adhere to the child's dosing schedule and
                          protocol evaluations. 2. Any clinical or
                          laboratory abnormality classified as Grade 2
                          or greater toxicity. 3. Grade 2 or greater
                          peripheral neuropathy or a significant
                          history of peripheral neuropathy. 4.
                          Inability to be on study for at least 12
                          months. 5. Inability to consume adequate oral
                          intake (defined as the inability to eat at
                          least 1 meal a day or to have 3 feedings a
                          day for newborns) because of chronic nausea,
                          emesis, or abdominal or esophageal
                          discomfort.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0208  Emtricitabine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0316  Lopinavir/Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 6 mg/kg qd, up to a
                          maximum of 200 mg qd. Drug 2:
                          Antiretroviral-naive patients: 12/3 mg/kg bid
                          if 7 or mto less than 15 kg; 10/2.5 mg/kg bid
                          if 15 or more to 40 or les400/100 mg bid if
                          greater than 40 kg
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 6 mg/kg, up to a
                          maximum of 200 mg. Drug 2:
                          Antiretroviral-naive patients: 24/6 mg/kg if
                          7 or more less than 15 kg; 20/5 mg/kg if 15
                          or more to 40 or less kg; 800mg if greater
                          than 40 kg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks. After the Week
                          48 study evaluations are completed,
                          individual patients may continue to receive
                          study medication (as provided by the sponsor)
                          until commercially available, as long as: 1)
                          their plasma HIV-1 RNA level is 400 or less
                          copies per ml, or 2) there is reliable
                          genotypic evidence to show a lack of viral
                          resistance to the study medication.
SUPPORTING AGENCY         Triangle Pharmaceuticals Inc.
LAST REVISION DATE        20010613
CALIFORNIA                USC School of Medicine / LA County Med Ctr
                          1640 Marengo St / HRA Building 3rd Floor Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 010620.
FLORIDA                   Univ of Miami PO Box 16960 Miami, FL
                          331016960 Amy Malmsberry [phone]
                          Recruiting 010620.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          010620.
NEW YORK                  St Luke's - Roosevelt Hosp Ctr 1111 Amsterdam
                          Ave / 411 - Suite 2D New York, NY 10025
                          Robert Warford [phone] Recruiting
                          010620.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010620.
NEW YORK                  New York Hosp / Cornell Med Ctr 525 East 68th
                          St / Box 296 New York, NY 10021 Anne Monroe
                          [phone] Recruiting 010620.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 010620.
OTHER                     Fundacion HUES Angel Pelutto 3932 1202 Buenos
                          Aires, Patercia Coll ( 54)114-9817777
                          Recruiting 010620.
OTHER                     Hospital del Nino Av Balboa y Calle 34 Panama
                          City, Maria Mercedes Castrejon (011) 50-7 225
                          8089 Recruiting 010620.
OTHER                     Instituto Mexicano de Investigacion Clinica
                          Durango 216 Col Roma , Eloy Margarita Aguilar
                          ( 5)25 -511 9111 Recruiting 010620.
OTHER                     Univ of Puerto Rico / Med Science Campus PO
                          Box 365067 San Juan, PR 00936 Carmen Velez
                          [phone] Recruiting 010620.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          010620.

22
UNIQUE IDENTIFIER         NIH/01397
PROTOCOL ID NUMBERS       NIAID ACTG A5103
PROTOCOL TITLE            Phase II, Randomized, Open-Label Study of
                          Switching to Protease Inhibitor-Sparing
                          Regimens for Improvement of Metabolic
                          Abnormalities.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare changes from baseline in
                          fasting non-high density lipoprotein
                          (non-HDL) cholesterol and fasting
                          triglyceride levels among the nevirapine
                          (NVP)-, abacavir (ABC)-, and efavirenz
                          (EFV)-containing regimens to Week 24.
GENERAL DESCRIPTION       RATIONALE: Protease inhibitor (PI)-containing
                          antiretroviral regimens are potent
                          suppressors of HIV replication. Increasingly,
                          metabolic abnormalities such as
                          hypercholesterolemia and triglyceridemia are
                          associated with PI use, reasons cited for
                          switching to PI-sparing regimens. Yet optimal
                          switch regimens that take into account both
                          improvements in side effects and continued
                          virologic suppression have not been defined.
                          This study will compare the effect on
                          chemical metabolic abnormalities of switching
                          to an all nucleoside regimen versus dual
                          nucleoside plus nonnucleoside reverse
                          transcriptase inhibitor (NNRTI) therapy.
                          Determining the effects of each regimen on
                          chemical metabolic abnormalities and
                          maintenance of virologic suppression will
                          define which of the switch strategies being
                          studied improves metabolic abnormalities
                          without compromising viral suppression.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified on the
                          basis of fasting non-HDL cholesterol and
                          triglyceride levels and on ritonavir- or
                          nonritonavir-containing pre-entry PI
                          regimens. Patients are assigned randomly to
                          add to their pre-entry regimen 1 of the
                          following 3 treatments: Arm A - ABC; Arm B -
                          NVP; or Arm C - EFV. Patients discontinue
                          pre-entry PIs after Day 14. Patients are
                          followed to determine the effect of the
                          maintenance regimens on fasting
                          non-high-density lipoprotein (HDL),
                          cholesterol, and triglycerides at Week 24.
                          Fasting total cholesterol, HDL cholesterol,
                          direct low-density lipoprotein, and
                          triglycerides are measured at Weeks 12, 24,
                          and 48. Fasting glucose, insulin, C-peptide,
                          apolipoproteins A-1 and B, lipoprotein a, and
                          homocysteine are measured at Weeks 24 and 48.
                          Anthropometrics, body mass index, and body
                          image are measured at Weeks 12, 24, and 48.
                          HIV viral load is measured at Weeks 2, 4, 8,
                          12, 16, 20, 24, 32, 40, and 48. If HIV RNA
                          stays below 200 copies/ml, therapy continues
                          unchanged. If confirmed HIV RNA of 200
                          copies/ml or higher is found, an HIV genotype
                          is obtained providing the viral load is
                          sufficient to yield results, the best medical
                          therapy is instituted (not supplied by the
                          study), and off treatment/on study follow-up
                          is continued. If patients are intolerant to a
                          study drug, an alternate study drug (ABC,
                          EFV, or NVP supplied by the study) is
                          permitted and switched treatment/on study
                          follow-up continued, or the best medical
                          therapy is instituted (not supplied by the
                          study), and off treatment/on study follow-up
                          is continued. Patients are followed until the
                          last patient enrolled has completed 48 weeks
                          on study
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Prevention of drug toxicity.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 342 patients. 114 patients
                          in each of 3 arms.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until the last
                          patient enrolled has completed 48 weeks on
                          study.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/342.
PROTOCOL DETAILS          STUDY DURATION: Approximately 1.5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (010216)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5103
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection, as documented by
                          any licensed ELISA test kit, and confirmed by
                          Western blot at any time prior to study
                          entry. HIV-1 culture, HIV-1 antigen, plasma
                          HIV-1 RNA or branched DNA (bDNA), or a second
                          antibody test by a method other than ELISA is
                          acceptable as an alternative confirmatory
                          test. 2. HIV-1 RNA below 400 copies/ml by
                          RT-PCR or HIV-1 below 500 copies/ml by bDNA
                          on at least 2 measurements performed during
                          the prior 6 months of entry separated by a
                          minimum of 8 weeks. Evaluations may have been
                          made by either an ACTG or a non-ACTG
                          laboratory. 3. Plasma HIV RNA below 50
                          copies/ml by Roche Amplicor UltraSensitive
                          assay, obtained from Roche-certified
                          laboratory, within 30 days prior to entry. 4.
                          CD4+ cell count of 200 copies/ml or more
                          obtained within 60 days prior to study entry
                          at any ACTG-certified laboratory.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 Within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 200 copies/ml Within
                          60 days prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN ULN Upper Limit of
                          Normal). Within 30 days prior to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60 %.
PATIENT INCLUSION CRIT.   OTHER: Fasting non-HDL cholesterol (total
                          cholesterol minus HDL cholesterol) > 180
                          mg/dl and/or fasting triglyceride > 250
                          mg/dl. Serum lipase <= 1.5 x ULN. Within 30
                          days prior to study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Negative
                          pregnancy test within 14 days of study entry
                          Not pregnant Abstinence or two effective
                          methods of birth control / contraception
                          during the study and for 90 days after.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable initial
                          antiretroviral therapy consisting of at least
                          3 agents and including 2 NRTIs and at least 1
                          PI. Stable antiretroviral therapy is defined
                          as no change in drugs for at least 6 months,
                          except the following changes in therapy are
                          permitted more than 60 days prior to entry:
                          1) alterations in dose or dosing frequency of
                          any agent(s) for nonvirologic reasons; 2) a
                          single substitution of at most 1
                          antiretroviral agent for nonvirologic reasons
                          (e.g., toxicity); 3) a single antiretroviral
                          treatment interruption of less than 7 days;
                          4) cumulative antiretroviral treatment
                          interruptions that do not exceed 28 days; and
                          5) change in formulation of agent(s) (e.g.,
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required/Recommended:
                          Treatment, maintenance, or chemoprophylaxis
                          with approved agents for OI as clinically
                          indicated (unless a prohibited medication).
                          Allowed: Topical antifungal agents. Allowed
                          with caution: 1. Clarithromycin due to
                          possible drug/drug interaction with
                          efavirenz. Alternative medications such as
                          azithromycin should be used. 2. Herbal
                          medications should be avoided. Patients
                          should report the use of these therapies. 3.
                          Alcoholic beverages.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Documented or suspected acute hepatitis
                          within 30 days prior to study entry. 2.
                          Serious illness (requiring systemic treatment
                          or hospitalization) unless therapy was
                          completed at least 14 days prior to entry, or
                          patients are clinically stable on therapy, in
                          the opinion of the investigator, for at least
                          14 days prior to study entry.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Drug or alcohol use
                          or dependence that, in the opinion of the
                          investigator, would interfere with patient
                          adherence to study treatment and monitoring.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any NNRTI. 2.
                          ABC. 3. Any candidate HIV vaccine or other
                          agent with potential immune-modulating
                          effects within 30 days prior to study entry,
                          including but not limited to dithiocarbamate
                          sodium, GM-CSF, immune globulin, interferons,
                          interleukins, isoprinosine, isotretinoin,
                          pentoxifylline, thalidomide, thymopentin, and
                          thymosin. 4. Systemic anticancer agents
                          within 30 days of entry. 5. Systemic
                          treatment with amiodarone, astemizole,
                          bepridil, ergot derivatives, itraconazole,
                          ketoconazole, midazolam, cisapride,
                          phenytoin, phenobarbital, propoxyphene,
                          warfarin, rifabutin, rifampin, triazolam, and
                          St. John's wort within 14 days prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Prohibited: 1.
                          Antiretroviral medications, other than PIs
                          during the first 2 weeks of the study,
                          study-supplied medications, and pre-entry
                          nucleoside reverse transcriptase inhibitors
                          (NRTIs) until dose-limiting toxicity or
                          virologic failure on the randomly assigned
                          treatment occurs. 2. New prescription or
                          nonprescription drugs that may affect
                          cholesterol or triglyceride levels, including
                          fibrate agents (e.g., gemfibrozil and
                          fenofibrate), niacin (at least 300 mg/day),
                          statin agents (e.g., pravastatin,
                          simvastatin, lovastatin, atorvastatin, and
                          cerivastatin), thiazolidinediones, metformin,
                          testosterone supplementation or therapeutic
                          doses of alpha-omega-3 fish oil, during the
                          first 24 weeks of the trial. For Week 25 and
                          beyond, pravastatin and/or either gemfibrozil
                          or fenofibrate are permitted. 3.
                          Investigational drugs except with specific
                          approval of the study chair/co-chairs. 4.
                          Systemic cytotoxic chemotherapy. 5.
                          Contraindicated medications, including
                          amiodaron
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: Allergy or
                          sensitivity to the study drugs or components
                          in their formulation.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0269  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0325
                          Lamivudine/Zidovudine/Abacavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm A: 300 mg bid.
                          Drug 2: Arm C: 600 mg qd. Drug 3: Arm B: 200
                          mg qd for 14 days, then 200 mg bid. Drug 4:
                          Arm A option for patients already on
                          lamivudine (3TC)/ZABC 300 mg/3TC 150 mg/ZDV
                          300 mg bid (if available)
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 600 mg.
                          Drug 3: 200 mg for 14 days, then 400 mg. Drug
                          4: ABC 600 mg/3TC 300 mg/ZDV 600 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral
OTHER TREATMENT INFO.     END POINT: Change in non-HDL cholesterol and
                          fasting triglyceride levels from baseline to
                          Week 24.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may discontinue
                          treatment for the following reasons: 1.
                          Drug-related toxicity. 2. Failure by the
                          patient to attend 3 consecutive clinic
                          visits. 3. Request by the patient. 4. Request
                          of the primary care provider if she/he thinks
                          the study is no longer in the best interest
                          of the patient. 5. Clinical reasons believed
                          life-threatening by the physician, even if
                          not addressed in the toxicity management of
                          the protocol. 6. Judgment by the investigator
                          that the patient is at significant risk of
                          failing to comply with the provisions of the
                          protocol as to cause harm to self or
                          seriously interfere with the validity of the
                          study results.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010712.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010717.

23
UNIQUE IDENTIFIER         FDA/01389
PROTOCOL ID NUMBERS       FDA 283H
PROTOCOL TITLE            An Open-Label Study to Assess the Anti-HIV-1
                          Activity of Tenofovir Disoproxil Fumarate
                          (TDF) in Antiretroviral-Naive Patients Who
                          Are Chronically Infected with HIV-1.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To evaluate the antiviral potency
                          and viral dynamics of tenofovir disoproxil
                          fumarate (TDF), a nucleotide analogue,
                          following 21 days of monotherapy in
                          antiretroviral therapy (ART)-naive patients.
                          Methodology: Patients receive TDF.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive TDF.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010711)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 21 days.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: GS-00-917
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented laboratory diagnosis of
                          HIV-1 infection (positive ELISA HIV-1
                          antibody test confirmed by Western blot, p24
                          assay, HIV-1 RNA, or culture). 2. Plasma
                          HIV-1 RNA level of 10,000 copies/ml or
                          greater. 3. CD4 count of 50 cells/mm3 or
                          greater.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 50 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase <= 1.5 x ULN (Upper
                          Limit of Normal). Patients with serum amylase
                          > 1.5 x ULN remain eligible if serum lipase
                          is <= 1.5 x ULN. Serum phosphate >= 2.2
                          mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test Abstinence
                          or agree to use two barrier methods of birth
                          control / contraception during the study and
                          one month after.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 65 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1. A
                          new AIDS-defining condition diagnosed within
                          30 days of baseline. 2. Active, serious
                          infections (other than HIV-1 infection)
                          requiring parenteral antibiotic therapy
                          within 15 days prior to screening. 3. History
                          of clinically significant renal or bone
                          disease.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: 1. Current alcohol
                          or substance abuse judged by the investigator
                          to potentially interfere with patient
                          compliance. 2. Current use of recreational
                          drugs.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Treatment with
                          any nucleoside reverse transcriptase
                          inhibitors, nucleotide reverse transcriptase
                          inhibitors (e.g., adefovir dipivoxil or TDF),
                          protease inhibitors, or nonnucleoside reverse
                          transcriptase inhibitors. 2. Vaccinations
                          within 30 days of baseline.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Nephrotoxic
                          agents, including aminoglycoside antibiotics,
                          cidofovir, cisplatin, foscarnet, IV
                          amphotericin B, IV vancomycin, oral and IV
                          ganciclovir, and valganciclovir; probenecid;
                          systemic chemotherapeutic agents; systemic
                          corticosteroids; interleukin-2; and
                          investigational drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Evidence of a
                          gastrointestinal malabsorption syndrome or
                          chronic nausea or vomiting, which may confer
                          an inability to receive orally administered
                          medication. 2. Malignancy other than Kaposi's
                          sarcoma or basal cell carcinoma. 3. Any other
                          clinical condition or prior therapy that, in
                          the opinion of the investigator, would make
                          the patient unsuitable for the program or
                          unable to comply with the dosing
                          requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0290  Tenofovir disoproxil
                          fumarate
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 21 days.
SUPPORTING AGENCY         Gilead Sciences Inc.
LAST REVISION DATE        20010711
NEW YORK                  Aaron Diamond AIDS Rsch Ctr / Rockefeller
                          Univ 1230 York Ave New York, NY 10021 Arlene
                          Hurley [phone] Recruiting 010511.

24
UNIQUE IDENTIFIER         NIH/01388
PROTOCOL ID NUMBERS       NIAID ACTG A5093
PROTOCOL TITLE            An Open-Label, Non-Randomized Study of
                          Pharmacokinetic Interactions Between
                          Depo-Medroxyprogesterone Acetate (DMPA,
                          Depo-Provera) and Selected Protease Inhibitor
                          (PI) and Nonnucleoside Reverse Transcriptase
                          Inhibitor (NNRTI) Therapies Among
                          HIV-Infected Women.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To evaluate the effect of selected
                          antiretroviral (ARV) therapies (nelfinavir
                          [NFV], efavirenz [EFV], indinavir [IDV] in
                          combination with ritonavir [RTV], and
                          nevirapine [NVP]) on the pharmacokinetics
                          (PK) of depo-medroxyprogesterone acetate
                          (DMPA) among HIV-infected patients using the
                          DMPA area under the concentration-time curve
                          (AUC) from baseline (Day 0) to Week 12. To
                          determine the effect of DMPA on the PK of
                          selected ARV therapies among HIV-infected
                          patients using the AUCs for these drugs at
                          baseline (Day 0) and Week 4.
GENERAL DESCRIPTION       RATIONALE: DMPA, an injectable depot
                          formulation of medroxyprogesterone (MPA), is
                          a commonly used form of progestin-only
                          contraception. Information is limited on the
                          specific P450 isozymes that metabolize MPA;
                          however, it appears that CYP3A4 is 1 pathway
                          of hepatic clearance. Drugs known to be
                          inhibitors of the CYP3A4 pathway (such as
                          protease inhibitors [PIs]) may lead to
                          elevated concentrations of MPA. Secondly, MPA
                          given as DMPA injections has been shown to
                          induce the activity of CYP3A4 by 25 percent.
                          It is possible that this action may result in
                          enhanced clearance of the substrates of
                          CYP3A4, including PIs and nonnucleoside
                          reverse transcriptase inhibitors (NNRTIs),
                          which in turn may result in reduced drug
                          exposure and possible ARV failure. This study
                          is designed to address the lack of
                          information on potential interactions between
                          PIs or NNRTIs and DMPA.
GENERAL DESCRIPTION       METHODOLOGY: Patients are enrolled into 1 of
                          5 arms based on their current ARV regimen:
                          Arm A (control group): No current ARVs or
                          receiving nucleoside reverse transcriptase
                          inhibitors (NRTIs) only. Arm B: NFV (1250 mg
                          bid or 750 mg tid) in combination with NRTIs.
                          Arm C: EFV (600 mg qd) in combination with
                          NRTIs. Arm D: IDV (800 mg bid) and RTV (100
                          mg bid or 200 mg bid) in combination with
                          NRTIs. Arm E: NVP (200 mg bid) in combination
                          with NRTIs. Acceptable NRTIs and any fixed
                          combination of these medications include:
                          zidovudine (ZDV), lamivudine, didanosine,
                          stavudine (d4T), zalcitabine, and abacavir;
                          concurrent therapy using ZDV and d4T is not
                          allowed. ARV therapy is not provided by this
                          study. One dose of DMPA is provided to all
                          patients at entry (Day 0) and an optional
                          dose of DMPA will be available at the final
                          visit (Week 12) for those who are interested
                          in continuing with DMPA outside of the
                          protocol and who do not experience adverse
                          events from the first DMPA injection.
                          Patients in Arms B, C, D, and E have
                          intensive pharmacokinetic sampling done at
                          entry and at Week 4 to measure ARV levels.
                          All patients have blood tests at Weeks 2, 4,
                          6, 8, 10, and 12 to measure levels of DMPA
                          and progesterone. In addition, tests to
                          monitor HIV-1 RNA levels, CD4 and CD8 counts,
                          hematology, blood chemistries, and liver
                          function are performed periodically.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination pharmacokinetics,
                          Combination and single pharmacokinetics, Drug
                          interactions, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 76 patients. 20 patients
                          in Arm B and 14 each in Arms A, C, D, and E.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/76.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (010416)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Nonrandomized Concurrent Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection documented by any
                          licensed ELISA test kit and confirmed by
                          Western blot, HIV-1 culture, HIV-1 antigen,
                          plasma HIV-1 RNA, or a second antibody test
                          by a method other than ELISA at any time
                          prior to study entry. 2. Plasma HIV-1 RNA
                          less than 10,000 copies/ml within 30 days
                          prior to study entry. 3. Last menstrual
                          period (LMP) less than 35 days prior to study
                          entry or, if LMP more than 35 days prior to
                          study entry, serum follicle-stimulating
                          hormone less than 40 MIU/ml. 4. Documentation
                          from primary care providers of patients who
                          are not receiving ARV therapy that they have
                          been counseled about the potential benefits
                          of such therapy within the 3 months prior to
                          study entry and, despite counseling, have
                          elected not to take ARV therapy at this time
                          nor in the foreseeable future. 5. CD4 cell
                          count greater than 200 cells/mm3 if receiving
                          ARV therapy, or CD4 cell count greater than
                          350 cells/mm3 if not receiving ARV therapy,
                          within 30 days prior to study entry. 6.
                          Normal ovarian function without bilateral
                          oophorectomy, and be premenopausal. 7. No
                          acute infections or other opportunistic
                          diseases requiring medication within 14 days
                          prior to study entry. 8. Agreement not to
                          participate in a conception process (defined
                          as active attempt to become pregnant or in
                          vitro fertilization) for the duration of the
                          study. 9. Consent of a parent or guardian if
                          under 18 years of age. 10. Documentation of
                          Pap smear within the 1 year prior to study
                          entry. Women with high-grade squamous
                          intraepithelial lesions on their Pap smear
                          result must have been or will need to be
                          referred for a colposcopy. Note: If
                          documentation of Pap smear result is not
                          available, then Pap smear must be performed
                          by either the site or the patient's primary
                          care provider. 11. Documentation of Hepatitis
                          B and C status. Note: If documentation of
                          Hepatitis B and C status is not available,
                          then Hepatitis B surface antigen and
                          hepatitis C core antibody should be performed
                          at the local site laboratory.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 Within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 200 cells/mm3 If
                          receiving ARV therapy, or CD4 > 350 cells/mm3
                          if not receiving ARV therapy, within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN (Upper Limit of
                          Normal) within 30 days prior to study entry.
                          Note: If patient is on indinavir, then total
                          bilirubin must be <= 2.0 x ULN within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase <= 1.5 x ULN within 30
                          days prior to study entry. International
                          normalized ratio (INR) <= 1.8 within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Negative pregnancy test within 30 days
                          of study entry Premenopausal.
PATIENT INCLUSION CRIT.   WEIGHT: Included: Weight within 25 percent of
                          ideal body weight and at least 40 kg within
                          30 days of study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable ARV
                          regimens for a minimum of 30 days prior to
                          study entry for patients receiving ARV.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Patient
                          intent to continue on current ARV regimens
                          (or lack thereof) for at least 3 months after
                          study entry. Allowed with caution: 1. Stable
                          doses of CYP 3A4 substrates if taken for
                          longer than 30 days prior to study entry,
                          including the following precautionary
                          medications: benzodiazepines, except
                          midazolam and triazolam that are prohibited;
                          bupropion; calcium channel blockers, except
                          diltiazem and verapamil that are prohibited;
                          fluconazole; HMG CoA reductase inhibitors
                          except pravastatin (i.e., atorvastatin,
                          cerivastatin, and fluvastatin, but not
                          lovastatin and simvastatin that are
                          prohibited); isoniazid; mexiletine; zaleplon;
                          and zolpidem. 2. Medications that potentially
                          interact with EFV, RTV, IDV, or NVP. Refer to
                          package inserts for potential drug
                          interactions that may require therapeutic
                          drug monitoring and/or adjustment of
                          concomitant medications.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Significant change (i.e., more than a 50
                          percent change) in tobacco smoking habit
                          within the 6 weeks prior to study entry.
                          Patients may have either stopped or started
                          smoking more than 6 weeks before study entry.
                          2. Invasive cancer of the reproductive tract,
                          undiagnosed vaginal bleeding, hypothyroidism
                          or hyperthyroidism, liver tumors, or serious
                          ocular disorders at any time prior to study
                          entry.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug or alcohol use or
                          dependence that, in the opinion of the
                          investigator, would interfere with adherence
                          to study requirements.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. ARV therapy
                          within 30 days prior to study entry in
                          patients who have chosen not to take ARV
                          therapy during the study. 2. DMPA within 180
                          days prior to study entry. 3. Other hormonal
                          therapies (MPA, oral contraceptive agents,
                          hormonal replacement therapy, or anabolic
                          therapies [e.g., nandrolone decanoate,
                          megestrol acetate]) within 30 days prior to
                          study entry. 4. Tenofovir, amprenavir, or
                          lopinavir/ritonavir within 30 days prior to
                          study entry. 5. Amiodarone, astemizole,
                          bepridil, buspirone, carbamazepine,
                          cisapride, clarithromycin, cyclosporine,
                          dihydroergotamine, ergotamine, erythromycin,
                          flecainide, glucocorticoids, Hypericum
                          perforatum (St. John's wort), itraconazole,
                          ketoconazole, lovastatin, midazolam,
                          nefazodone, phenobarbital, phenytoin,
                          pimozide, pioglitazone, propafenone,
                          propofol, quinidine, rifabutin, rifampin,
                          rosiglitazone, simvastatin, tacrolimus,
                          terfenadine, ticlopidine, or triazolam,
                          within 30 days prior to study entry. 6.
                          Initiation, di
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Nucleoside analogue monotherapy. 2.
                          Amiodarone, astemizole, bepridil, buspirone,
                          carbamazepine, cimetidine, cisapride,
                          clarithromycin, cyclosporine,
                          dihydroergotamine, diltiazem, ergotamine,
                          erythromycin, flecainide, glucocorticoids,
                          grapefruit juice, Hypericum perforatum (St.
                          John's wort), itraconazole, ketoconazole,
                          lovastatin, midazolam, nefazodone,
                          phenobarbital, phenytoin, pimozide,
                          pioglitazone, propafenone, propofol,
                          quinidine, rifabutin, rifampin,
                          rosiglitazone, simvastatin, tacrolimus,
                          terfenadine, ticlopidine, triazolam, and
                          verapamil. 3. Initiation, discontinuation, or
                          change of therapy of CYP 3A4 substrates
                          during the study, including the following
                          precautionary medications: benzodiazepines,
                          except midazolam and triazolam that are
                          prohibited; bupropion; calcium channel
                          blockers, except diltiazem and verapamil that
                          are prohibited; fluconazole; HMG CoA
                          reductase inhibitors except pravastatin
                          (i.e., atorvastatin, cerivastatin, and
                          fluvastati
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Less than 30 days
                          post-partum at study entry. 2. Hysterectomy
                          or bilateral oophorectomy. 3. Inability to
                          adhere to the ARV medications while on study,
                          in the opinion of the investigator. 4.
                          Inability to abstain from alcohol 1 day prior
                          to and during the 10-hour PK on Day 0 and
                          Week 4. 5. Hypersensitivity to DMPA, MPA, or
                          any of the other ingredients in DMPA.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0332  Medroxyprogesterone acetate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0269  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0116  Nevirapine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: All Arms: 150 mg on
                          Day 0 and optionally at Week 12. Drug 2: Arm
                          B: 1250 mg bid or 750 mg tid. Drug 3: Arm C:
                          600 mg qd. Drug 4: Arm D: 800 mg bid with
                          ritonavir. Drug 5: Arm D: 100 or 200 mg bid
                          with indinavir. Drug 6: Arm E: 200 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 2: 2250 to 2500 mg. Drug
                          3: 600 mg. Drug 4: 1600 mg. Drug 5: 200 or
                          400 mg. Drug 6: 400 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Oral. Drug 3: Oral. Drug 4: Oral. Drug 5:
                          Oral. Drug 6: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 weeks.
OTHER TREATMENT INFO.     END POINT: Pharmacokinetics, as measured by
                          AUC of DMPA from baseline (Day 0) to Week 12
                          and AUCs for NFV (Arm B), EFV (Arm C), IDV in
                          combination with RTV (Arm D), and NVP (Arm E)
                          on baseline (Day 0) and Week 4.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. The patient or
                          legal guardian refuses further treatment
                          and/or follow-up evaluations. 2. The
                          investigator decides that continued
                          participation in the study would be harmful
                          to the patient's health or well-being. 3. The
                          patient requires treatment with medications
                          that are disallowed while on this study. 4.
                          The patient fails to comply with the study
                          requirements so as to cause harm to self or
                          seriously interfere with the validity of the
                          study results. 5. The patient becomes
                          pregnant.
OTHER TREATMENT INFO.     MODIFICATION: Efavirenz is usually taken in
                          the evening; however, for the purpose of this
                          study, patients switch their dosing time of
                          EFV to a once-daily morning schedule for the
                          3 days prior to the PK assessment at Day 0
                          and Week 4. The switch occurs the morning
                          following the last dose, which should
                          separate the doses by 12 hours, to prevent a
                          significant fall in the EFV levels. These
                          patients remain on morning dosing until the
                          day of the PK assessment. On the day of the
                          PK study, patients hold their morning doses
                          of EFV until after the necessary blood work
                          has been obtained.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010627.

25
UNIQUE IDENTIFIER         NIH/01384
PROTOCOL ID NUMBERS       NINR 6510
PROTOCOL TITLE            The Healthy Life Choices Project.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To investigate the efficacy of a
                          dietary intervention using normal foods and
                          behavior skills training in reducing the
                          frequency of diarrhea (soft or loose stools)
                          in HIV-positive individuals. Methodology:
                          Patients are randomized to 1 of 2 arms within
                          each cohort: Cohort A: Malabsorption Study.
                          Arm 1: Combined nutrition knowledge
                          consisting of an intervention diet and
                          cognitive/behavioral skill training for
                          dietary behavior change. Arm 2: Intervention
                          program which focuses on HIV self-care issues
                          and contains general nutrition knowledge
                          (control group). Cohort B: Expanded Study
                          (diarrhea due to side effects of anti-HIV
                          medications). Arm 1: Combined nutrition
                          knowledge consisting of an intervention diet
                          and cognitive/behavioral skill training for
                          dietary behavior change. Arm 2: Intervention
                          program which focuses on HIV self-care issues
                          and contains general nutrition knowledge
                          (control group). All arms are identical in
                          duration and intensity and involve various
                          interactive learning activities. Patients are
                          seen at an intake screening session and on
                          Weeks 1, 2, 3, 8, 16, and 24. Measures of
                          physical functioning, daily bowel movement,
                          diet and anti-diarrheal medication diaries,
                          process mediator variables (knowledge
                          attitudes, subjective norms, control belief,
                          and intentions), and quality-of-life data are
                          collected at pre-intervention, immediately
                          post-intervention, and at each follow-up
                          session. Patients receive monetary
                          compensation for participation.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to 1 of
                          2 arms within each cohort: Cohort A:
                          Malabsorption Study. Arm 1: Combined
                          nutrition knowledge consisting of an
                          intervention diet and cognitive/behavioral
                          skill training for dietary behavior change.
                          Arm 2: Intervention program which focuses on
                          HIV self-care issues and contains general
                          nutrition knowledge (control group). Cohort
                          B: Expanded Study (diarrhea due to side
                          effects of anti-HIV medications). Arm 1:
                          Combined nutrition knowledge consisting of an
                          intervention diet and cognitive/behavioral
                          skill training for dietary behavior change.
                          Arm 2: Intervention program which focuses on
                          HIV self-care issues and contains general
                          nutrition knowledge (control group). All arms
                          are identical in duration and intensity and
                          involve various interactive learning
                          activities. Patients are seen at an intake
                          screening session and on Weeks 1, 2, 3, 8,
                          16, and 24. Measures of physical functioning,
                          daily bowel movement, diet and anti-diarrheal
                          medication diaries, process mediator
                          variables (knowledge attitudes, subjective
                          norms, control belief, and intentions), and
                          quality-of-life data are collected at
                          pre-intervention, immediately
                          post-intervention, and at each follow-up
                          session. Patients receive monetary
                          compensation for participation.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010413)
PROTOCOL DETAILS          STUDY INTENT: Strategy determination.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: Diarrhea.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: NIH 2652
PROTOCOL DETAILS          STUDY DESIGN: Random Allocation; Single-Blind
                          Method; Cohort Study; Randomized Control
                          Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection/AIDS. 2. Diarrhea
                          (soft or loose stools) an average of 3 times
                          per day for at least 3 weeks. 3. A negative
                          stool culture result for all pathogens.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
SUPPORTING AGENCY         Natl Institute of Nursing Research.
LAST REVISION DATE        20010413
NEW YORK                  Columbia Univ School of Nursing / Center for
                          AIDS Research 617 West 168th Street New York,
                          NY 10032 Ann Chung [phone] Recruiting
                          010413.

26
UNIQUE IDENTIFIER         NIH/01383
PROTOCOL ID NUMBERS       NCCAM 8343
PROTOCOL TITLE            The Acupuncture/Moxibustion Study.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To test the alternative treatment
                          strategies, acupuncture and moxibustion, to
                          reduce the frequency of chronic diarrhea
                          among HIV-positive individuals. Methodology:
                          Patients are randomized to 1 of 4 treatment
                          conditions: Condition 1: Patients receive
                          true acupuncture and true moxibustion.
                          Condition 2: Patients receive true
                          acupuncture and placebo moxibustion.
                          Condition 3: Patients receive true
                          moxibustion and sham acupuncture. Condition
                          4: Patients receive sham acupuncture and
                          placebo moxibustion (control group). Patients
                          attend a total of 20 scheduled sessions over
                          a period of 24 weeks. All patients complete
                          daily bowel movement and medication diaries
                          for the duration of the study. Measurement of
                          quality of life and level of functioning is
                          taken at Sessions 1, 10, 19, and 20. All
                          interventions are implemented by licensed
                          acupuncturists trained in Traditional Chinese
                          Medicine. Patients receive monetary
                          compensation for participation.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to 1 of
                          4 treatment conditions: Condition 1: Patients
                          receive true acupuncture and true
                          moxibustion. Condition 2: Patients receive
                          true acupuncture and placebo moxibustion.
                          Condition 3: Patients receive true
                          moxibustion and sham acupuncture. Condition
                          4: Patients receive sham acupuncture and
                          placebo moxibustion (control group). Patients
                          attend a total of 20 scheduled sessions over
                          a period of 24 weeks. All patients complete
                          daily bowel movement and medication diaries
                          for the duration of the study. Measurement of
                          quality of life and level of functioning is
                          taken at Sessions 1, 10, 19, and 20. All
                          interventions are implemented by licensed
                          acupuncturists trained in Traditional Chinese
                          Medicine. Patients receive monetary
                          compensation for participation.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010413)
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: Diarrhea.
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Placebo-Controlled Trial; Random Allocation;
                          Parallel Designs; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection/AIDS. 2. Chronic
                          diarrhea (soft or loose stools) 3 times per
                          day for at least 3 weeks. 3. Documentation,
                          from their primary care provider, confirming
                          HIV status and negative stool test for
                          pathogens. 4. Successful completion of a mini
                          mental-status exam.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Patients on
                          antiretroviral medications must have
                          completed 8 weeks of a stable regimen.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Patients who
                          are receiving acupuncture and/or moxibustion
                          (must interrupt in order to participate).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Inability to
                          complete a modified mini mental-state
                          examination, which is used to assess the
                          individual's mental state. Since the
                          intervention proposed requires a patient's
                          full attention and memory recall, a short
                          mental check is essential. 2. Acute medical
                          condition that would require acute medical
                          attention. 3. Plans to travel or other
                          activity that would preclude attending the
                          planned visits or accurately recording the
                          daily information.
SUPPORTING AGENCY         Natl Ctr for Complementary and Alternative
                          Medicine.
LAST REVISION DATE        20010413
NEW YORK                  Columbia Univ School of Nursing / Center for
                          AIDS Research 617 West 168th Street New York,
                          NY 10032 Ann Chung [phone] Recruiting
                          010413.

27
UNIQUE IDENTIFIER         NIH/01382
PROTOCOL ID NUMBERS       NINR 9941
PROTOCOL TITLE            The Acupressure Study.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To test the effectiveness of
                          acupressure for the relief of nausea and
                          vomiting in persons with HIV/AIDS.
                          Methodology: Patients attend 4 acupressure
                          sessions and wear acupressure wristbands for
                          1 week. Patients keep a diary of medications
                          and nausea/vomiting symptoms, and fill out
                          questionnaires. No medication is given as
                          part of this study. Patients receive monetary
                          compensation.
GENERAL DESCRIPTION       METHODOLOGY: Patients attend 4 acupressure
                          sessions and wear acupressure wristbands for
                          1 week. Patients keep a diary of medications
                          and nausea/vomiting symptoms, and fill out
                          questionnaires. No medication is given as
                          part of this study. Patients receive monetary
                          compensation.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010413)
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Nausea/vomiting an
                          average of 2 times per day for at least 1
                          week.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
SUPPORTING AGENCY         Natl Institute of Nursing Research.
LAST REVISION DATE        20010413
NEW YORK                  Columbia Univ School of Nursing / Center for
                          AIDS Research 617 West 168th Street New York,
                          NY 10032 Bernadette Capili [phone]
                          Recruiting 010413.

28
UNIQUE IDENTIFIER         FDA/01381
PROTOCOL ID NUMBERS       FDA B014
PROTOCOL TITLE            A Phase 1b Multicenter Double-Blind,
                          Placebo-Controlled, Randomized Study on the
                          Safety and Tolerability of Z-100 in Early
                          HIV-1 Infected Patients.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Treatment IND
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To determine the safety of Z-100 in
                          HIV patients who are either treatment naive
                          or treatment experienced, who have elected to
                          discontinue highly active antiretroviral
                          therapy (HAART)16 weeks or longer.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010413)
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: Zeria Protocol
                          85D10104
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Be HIV-1 positive and asymptomatic. 2. Be
                          treatment naive or treatment experienced and
                          have discontinued HAART at least 16 weeks
                          prior to screening, have demonstrated stable
                          HIV-1 RNA levels on at least 2 separate
                          timepoints 1 month apart prior to screening,
                          and have demonstrated stable CD4 levels on at
                          least 2 separate timepoints 1 month apart
                          prior to screening. 3. Have HIV-1 RNA levels
                          of 2,000 to 50,000 counts/ml within 2 weeks
                          of randomization. 4. Have CD4 counts of 300
                          to 800 cells/mm within 2 weeks of
                          randomization.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 300 to 800 cells/mm3
                          Within 2 weeks of randomization.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry Not pregnant Abstinence or
                          effective (approved) method of birth control.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Tuberculosis. 2. Severe malabsorption or
                          severe chronic diarrhea within 4 weeks of
                          randomization. 3. Hypersensitivity to the
                          study drug or drug class, as defined by a PPD
                          of equal to or greater than 20 mm at
                          baseline.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: History of alcohol
                          or drug abuse, unless the investigator does
                          not believe that it will interfere with the
                          ability to adhere to the requirements of this
                          protocol.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          (localized radiation therapy is permitted)
                          within 30 days before randomization.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. HAART within
                          16 weeks prior to screening. 2. Any other
                          immunomodulator or investigational agents
                          within 60 days prior to randomization. 3. Any
                          vaccination within 15 days before
                          randomization. 4. Cytotoxic chemotherapeutic
                          agents within 30 days before randomization.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded:
                          Anti-retroviral medication.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1.Failure of HAART
                          treatment. 2. Opportunistic infection or
                          malignancy. 3. Severe laboratory
                          abnormalities, or cardiac, hepatic, renal, or
                          neurological disorders. 4. Inadequately
                          controlled seizure disorder. 5. Mental
                          condition rendering the patient unable to
                          understand the nature, scope, and possible
                          consequences of the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0342  Z-100
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 2 x per week, every
                          3 to 4 days for 8 weeks
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous injection
SUPPORTING AGENCY         Quintiles Inc.
LAST REVISION DATE        20010413
CALIFORNIA                UCSF - San Francisco Gen Hosp 635 Potrero Ave
                          San Francisco, CA 94110 Anna Smith
                          [phone] Recruiting 010413.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Patrick Milne
                          [phone] Recruiting 010627.
TEXAS                     Univ TX Med Branch 1012 Texas Ave / Graves
                          Bldg Galveston, TX 77555 Suzanne Lanier
                          [phone] Recruiting 010413.

29
UNIQUE IDENTIFIER         NIH/01380
PROTOCOL ID NUMBERS       NIAID ACTG A5102
PROTOCOL TITLE            An Open-Label, Pilot Study Utilizing CD4
                          T-Cell Counts Lower Than 350 Cells/mm3 as the
                          Threshold for Restarting Therapy with Potent
                          Antiretroviral Therapy with or without
                          Interleukin-2 to Determine the Effect of
                          Pulse Therapy on the Characteristics of
                          Treatment Interruptions.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Treatment IND
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To assess the CD4 T-cell count at
                          the end of Step 1 (interleukin-2 [IL-2]
                          versus no IL-2 Step) and the slope of the
                          decline in CD4 T-cell count during Step 2
                          (treatment interruption).
GENERAL DESCRIPTION       RATIONALE: An approach to reconstituting the
                          diminished immune system caused by HIV is the
                          use of potent antiretroviral therapy (ART) in
                          conjunction with IL-2. IL-2 is a cytokine
                          secreted by activated T lymphocytes that
                          regulates the proliferation and
                          differentiation of lymphocytes, including CD4
                          and CD8 T-cells. Although treatment with IL-2
                          can cause transient increases in HIV-1 RNA
                          levels, clinical studies with IL-2 have
                          revealed no long-term adverse effect upon the
                          viral load. Indeed, when administered in the
                          setting of maximal viral suppression induced
                          by potent ART, IL-2 therapy might help purge
                          the host's latent viral reservoir through
                          activation of resting lymphocytes harboring
                          provirus. Another approach to the management
                          of HIV infection is strategic treatment
                          interruption. Results from small pilot trials
                          suggest that HIV replication can be highly
                          suppressed over consecutive courses following
                          short treatment interruptions and that CD4
                          T-cell counts can be maintained with perhaps
                          some positive effect on HIV-specific
                          immunity. This study evaluates intermittent
                          potent ART, started and interrupted based on
                          CD4 cell counts, with or without IL-2, as an
                          alternative approach to the chronic treatment
                          of HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified, based
                          on lifetime CD4 T-cell nadir, to 1 of 3
                          strata: 1) nadir less than or equal to 200
                          CD4 cells/mm3; 2) nadir greater than 200 CD4
                          cells/mm3; or 3) no documented nadir count
                          available. Patients are randomized equally to
                          2 arms: Arm A: Pulses of potent ART and
                          cycles of IL-2. Arm B: Pulses of potent ART
                          alone. This study has 7 steps. Clinical and
                          laboratory assessments are performed
                          periodically per protocol guidelines.
                          Patients meeting CD4 T-cell or HIV-1 RNA
                          eligibility criteria can register to each
                          successive step within 6 weeks after
                          completing the evaluations on the last visit
                          of the previous step. Step 1: Arm A patients
                          receive potent ART plus IL-2, administered
                          twice a day for 5 days (equal to 1 cycle)
                          every 8 weeks for 3 cycles. Arm B patients
                          receive potent ART alone. Step 2: Treatment
                          interruption, defined as the withdrawal of
                          both IL-2 therapy and/or potent ART, occurs
                          for patients in both arms. Step 3: Patients
                          in both arms receive potent ART alone. Step 4
                          repeats Step 1, Step 5 repeats Step 2, Step 6
                          repeats Step 3, and Step 7 repeats Step 1.
                          All patients will have a diphtheria and
                          tetanus toxoid immunization (not provided by
                          the study) once, in Step 1 at Week 4.
                          Patients must provide their own potent ART
                          for the duration of the study. A5109s is a
                          limited-center substudy designed to ascertain
                          whether viral replication impairs lymphocyte
                          proliferation in vivo. Patients may register
                          to the substudy immediately after registering
                          to Step 2 of the main study
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy, Drug dosing schedule, Drug efficacy,
                          Immunology, Immunotherapy, Treatment IND,
                          Strategy determination.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 80 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1/80 010724.
PROTOCOL DETAILS          STUDY DURATION: Approximately 196 weeks (4
                          years).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (010315)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5102. Substudy
                          AACTG A5109s
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Parallel Designs;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection, as documented by
                          any licensed ELISA test kit and confirmed by
                          Western blot at any time prior to study
                          entry. A positive HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA is
                          acceptable as an alternative confirmatory
                          test. 2. CD4 T-cell count greater than or
                          equal to 500 cells/mm3 obtained within 90
                          days prior to study entry (screening visit)
                          at any ACTG-certified flow laboratory. Note:
                          Patients with a CD4 T-cell count less than
                          500 cells/mm3 at preentry or entry are still
                          eligible for study entry as long as the
                          screening visit value is 500 cells/mm3 or
                          greater. 3. HIV-1 RNA less than 400 copies/ml
                          within 90 days prior to study entry
                          (screening visit) by the UltraSensitive
                          Amplicor HIV-1 Monitor assay as documented by
                          a laboratory report from a Roche-certified
                          laboratory. 4. HIV-1 RNA less than 200
                          copies/ml within 30 days prior to study entry
                          (preentry) by the UltraSensitive Amplicor
                          HIV-1 Monitor assay as documented by a
                          laboratory report from a Roche-certified
                          laboratory. 5. Negative pregnancy test
                          performed within 30 days before initiating
                          study-specified medications and again at Day
                          0, if female and able to give birth. 6.
                          Agreement not to participate in a conception
                          process (defined as active attempt to become
                          pregnant or to impregnate, sperm donation, in
                          vitro fertilization, etc.). If participating
                          in sexual activity that could lead to
                          pregnancy, the female patient/male partner
                          must use an adequate form of contraception (1
                          barrier method, with or without a
                          hormonal-based method) while receiving
                          protocol-specified medications and for 1
                          month after stopping the medications. 7.
                          Willingness to participate in the study for
                          up to 4 years or longer. 8. Willingness of
                          patient's primary care provider to have the
                          patient in the study and to comply with
                          Department of Health and Human Services'
                          (DHHS) guidelines for potent ART.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 Within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 500 cells/mm3 Within
                          90 days prior to study entry (screening
                          visit).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 x ULN Unless elevation is
                          due to elevated indirect bilirubin in a
                          patient receiving indinavir and in the
                          absence of other evidence of significant
                          liver disease, within 30 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 90 Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase: <= 1.5 x ULN (if serum
                          amylase is > 1.5 x ULN, pancreatic amylase or
                          lipase must be <= 1.5 x ULN), within 30 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 30 days after Not pregnant
                          Negative pregnancy test.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Local
                          radiation for malignancy.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable potent ART
                          for 3 months or greater immediately prior to
                          entry. Note: Potent ART is currently defined
                          as 3 or more antiretroviral agents or dual
                          protease inhibitors. Allowed: Calcium channel
                          blockers or beta-blockers, for patients with
                          isolated hypertension without active cardiac
                          disease.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required:
                          Antiretroviral medications. Patients must
                          provide their own antiretroviral drugs. No
                          restrictions will be placed on the potent
                          antiretroviral drug combinations. However, it
                          is strongly recommended that they involve
                          FDA-approved medications used in accordance
                          with the most recent DHHS treatment
                          recommendations. Patients will not be
                          required to use the same potent ART
                          throughout the study. Allowed: 1. Stable
                          thyroid medication. 2. Calcium channel
                          blockers or beta-blockers, for patients with
                          isolated hypertension without active cardiac
                          disease. Allowed with caution: Iodinated
                          contrast dye for patients assigned to Arm A.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Any AIDS-defining illness with the exception
                          of minimal (less than 10 lesions) cutaneous
                          Kaposi's sarcoma. Note: Patients with a
                          history of a CD4 T-cell count less than 200
                          cells/ml but who have not had an
                          AIDS-defining illness are still eligible. 2.
                          Treatment failure (defined as HIV-1 RNA level
                          greater than or equal to 500 copies/ml on 2
                          occasions more than 6 months after starting a
                          regimen that includes either a protease
                          inhibitor or a nonnucleoside reverse
                          transcriptase inhibitor). Note: Patients
                          taking their first potent ART who may have
                          previously taken a single- or dual-nucleoside
                          regimen (with viremia) before starting their
                          first regimen are eligible. 3. Autoimmune
                          disease, including inflammatory bowel
                          disease, psoriasis, and optic neuritis. 4.
                          Major organ transplantation. 5. Clinically
                          significant neurological disorder either
                          diagnosed or occurring within 1 year prior to
                          study entry that in the opinion of the
                          principal investigator would affect the
                          patient's study compliance or safety. 6.
                          Severe systemic adverse reaction to
                          diphtheria t
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          substance abuse that, in the opinion of the
                          investigator, will interfere with adherence
                          to study requirements.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Immunomodulatory therapy within 4 weeks prior
                          to study entry including but not limited to
                          drugs such as systemic corticosteroids,
                          interferons, interleukins, thalidomide,
                          granulocyte-macrophage colony-stimulating
                          factor, dinitrochlorobenzene, inosiplex,
                          polyribonucleoside, ditiocarb, IV
                          gammaglobulin, or human growth hormone. 2.
                          Hydroxyurea within 3 months prior to study
                          entry. 3. Any systemic treatment with rhIL-2.
                          4. Treatment for active cardiac disease with
                          any of the following medications within 30
                          days prior to study entry: antianginal agents
                          such as nitrates, calcium channel blockers,
                          and beta-blockers, or antiarrhythmic agents
                          such as digitalis and afterload reducers. 5.
                          Astemizole, midazolam, and triazolam within 2
                          weeks prior to study entry. 6. Systemic
                          corticosteroids for 4 weeks or greater within
                          3 months prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiarrhythmic agents and antianginal agents,
                          such as nitrates, beta-blockers, and calcium
                          channel blockers (e.g., nifedipine,
                          verapamil, diltiazem, amlodipine, and
                          bepridil). 2. Systemic or local toxic
                          chemotherapy. 3. Astemizole. 4. Midazolam. 5.
                          Triazolam. 6. Other cytokines except for
                          erythropoietin. 7. Immunomodulatory therapy.
                          8. Systemic corticosteroids administered for
                          4 weeks or greater. 9. Hydroxyurea.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Any AIDS-defining
                          illness with the exception of minimal (less
                          than 10 lesions) cutaneous Kaposi's sarcoma.
                          2. Significant cardiac insufficiency (New
                          York Heart Association class above 2). Note:
                          Patients with isolated hypertension or
                          elevated plasma lipids but no cardiac disease
                          are eligible. 3. Any malignancy requiring
                          systemic or local toxic chemotherapy. 4.
                          Thyroid disease that has not been controlled
                          with medication for 3 months or greater prior
                          to study entry. 5. Uncontrolled diabetes
                          mellitus (defined as fasting blood glucose
                          greater than 126 mg/dl or random blood
                          glucose levels greater than 200 mg/dl on at
                          least 2 occasions within 6 months prior to
                          study entry). 6. Clinically significant
                          respiratory or gastrointestinal disease that,
                          in the opinion of the principal investigator,
                          might affect patient safety. 7. Psychiatric
                          illness that, in the opinion of the
                          investigator, will interfere with adherence
                          to study requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm A, Steps 1, 4,
                          and 7: 4.5 MIU bid x 5 days (1 cycleevery 8
                          weeks for 3 cycles
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous injection
OTHER TREATMENT INFO.     END POINT: The slope and intercept of the CD4
                          T-cell count during Step 2.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Drug-related
                          toxicity to the potent ART regimen requiring
                          that potent ART be stopped completely. 2.
                          Inability to tolerate an IL-2 dose of at
                          least 1.5 MIU twice daily (patients in Arm
                          A). 3. Development of an exclusionary
                          condition. 4. Pregnancy. 5. Use of prohibited
                          concomitant medications. 6. Failure to
                          maintain a CD4 cell count of 500 cells/mm3 or
                          greater at the conclusion of Step 1. 7.
                          Failure to achieve a CD4 count of 500
                          cells/mm3 or greater at the conclusion of
                          Step 4. 8. Reinitiation of potent ART prior
                          to achieving a CD4 T-cell count under 350
                          cells/mm3 on 2 consecutive visits during
                          Steps 2 and 5. 9. Failure to achieve an HIV-1
                          RNA count under 200 copies/ml at Week +24 of
                          Steps 3 and 6. 10. Failure to attend 2
                          consecutive clinic visits (unless approved by
                          the chair). 11. Failure to register to each
                          successive step within 6 weeks from
                          completing the evaluations on the last visit
                          of the previous step. 12. Request by the
                          patient to withdraw. 13. Request of the
                          primary care provider if she/he thinks the
                          study is no longer in the best interest of
                          the patient. 14. Clinical reasons believed
                          life-threatening by the physician, even if
                          not addressed in the toxicity management
                          section of the protocol. 15. Patient is
                          judged by the investigator to be at
                          significant risk of failing to comply with
                          the provisions of the protocol so as to cause
                          harm to self or seriously interfere with the
                          validity of the study results.
OTHER TREATMENT INFO.     MODIFICATION: For patients in Arm A,
                          administration and/or dose of IL-2 can be
                          modified because of toxicity in accordance
                          with protocol guidelines. Patients who
                          discontinue IL-2 but who wish to remain on
                          study may do so with the approval of the
                          study chair. These patients can remain on
                          study, off treatment for the remainder of the
                          study following the same evaluations as
                          scheduled for Arm B patients.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010702.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 010730.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 010723.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 010702.
MISSOURI                  Washington Univ / St Louis Connect Care 4511
                          Forest Park Parkway / Suite 304 Saint Louis,
                          MO 63108 Mike Klebert [phone]
                          Recruiting 010712.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          010712.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 010618.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 010618.

30
UNIQUE IDENTIFIER         NIH/01378
PROTOCOL ID NUMBERS       NIAID ACTG A5082
PROTOCOL TITLE            A Randomized, Double-Blind,
                          Placebo-Controlled Study of Metformin and
                          Rosiglitazone, Alone or in Combination, in
                          HIV-Infected Subjects with Fasting
                          Hyperinsulinemia and Elevated Waist/Hip
                          Ratio.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine the effects of
                          metformin and rosiglitazone on fasting
                          insulin levels and insulin area under the
                          curve (AUC) in response to an oral glucose
                          tolerance test (OGTT) by comparing each
                          active treatment group (metformin alone,
                          rosiglitazone alone, or the combination) to
                          placebo treatment. To determine the effects
                          of metformin and rosiglitazone, alone and in
                          combination, on visceral fat area by
                          comparing each active treatment group to
                          placebo treatment. To evaluate the safety of
                          metformin and rosiglitazone, alone and in
                          combination.
GENERAL DESCRIPTION       RATIONALE: Recent studies have documented
                          hyperglycemia, insulin resistance, and
                          glucose intolerance in a seemingly increasing
                          proportion of patients with HIV infection.
                          Other studies have described a variety of
                          syndromes of fat accumulation and fat loss,
                          including abdominal obesity. Although
                          initially attributed specifically to protease
                          inhibitors (PI), these abnormalities also
                          have been observed in
                          antiretroviral-experienced but PI-naive
                          patients. Hyperinsulinemia and abdominal
                          obesity are strong independent risk factors
                          for coronary artery disease. In non-infected
                          patients, metformin and thiazolidinediones
                          have been shown to reduce insulin resistance
                          by different mechanisms and also to reduce
                          visceral adiposity. This study investigates
                          the use of metformin and rosiglitazone, a
                          member of the thiazolidinedione class, in
                          HIV-infected patients with hyperinsulinemia
                          and central fat accumulation.
GENERAL DESCRIPTION       METHODOLOGY: At study entry, clinical and
                          laboratory assessments are performed. A
                          standard OGTT, with plasma samples drawn over
                          120 minutes, will be performed for glucose
                          and insulin determinations. After completion
                          of entry evaluations, patients are assigned
                          randomly to 1 of 4 double-blinded treatment
                          arms: Arm A: Metformin plus rosiglitazone
                          placebo. Arm B: Metformin placebo plus
                          rosiglitazone. Arm C: Metformin plus
                          rosiglitazone. Arm D: Metformin placebo plus
                          rosiglitazone placebo. Patients who are still
                          on study drugs at Week 16 (at either full or
                          reduced dose) are switched to the open-label
                          phase to receive the combination of metformin
                          and rosiglitazone through Week 32. Patients
                          have evaluations at Weeks 2, 4, 8, 12, 16,
                          18, 20, 24, 28, and 32. Safety indices,
                          fasting insulin and glucose levels, and
                          visceral fat are assessed.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Adverse effects, Combination
                          and single drug therapy, Drug efficacy, Drug
                          safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 160 patients. 128 male
                          patients (32 in each of 4 arms) and up to 32
                          female patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 32 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/160.
PROTOCOL DETAILS          STUDY DURATION: One-year accrual, estimated,
                          plus 32 weeks of drug administratio
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 10
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (010316)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5082
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Open Label;
                          Placebo-Controlled Trial; Random Allocation;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2. HIV-1 RNA
                          less than 10,000 copies/ml within 30 days of
                          study entry. 3. Waist-to-hip ratio greater
                          than 0.95 for males and 0.85 for females or
                          waist circumference greater than 100 cm. 4.
                          Fasting serum insulin greater than 15 IU/ml
                          from the AACTG Central Metabolic Laboratory
                          within 30 days of study entry. 5.
                          Self-reported changes in fat distribution
                          during the course of their HIV disease. 6.
                          Agreement not to participate in a conception
                          process (defined as active attempt to become
                          pregnant or to impregnate, sperm donation, in
                          vitro fertilization, etc.). If participating
                          in sexual activity that could lead to
                          pregnancy, the female study patient/male
                          partner must use a combination of 2
                          contraception methods (1 barrier) while
                          receiving protocol-specified medications and
                          for at least 30 days after stopping the study
                          medications. Female study patients who are
                          not of reproductive potential or whose male
                          partner is sterile for any reason are
                          eligible without requiring the use of
                          contraception.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.1 g/dl for men and >= 8.9
                          g/dl for women, within 30 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 x ULN ULN (Upper Limit of
                          Normal), within 30 days prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.5 x ULN Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.4 mg/dl Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Lactate <= 1.5 X ULN, within 30 days
                          prior to study entry. Fasting plasma glucose
                          <= 126 mg/dl, within 30 days prior to study
                          entry. Testosterone > 400 ng/dl, within 30
                          days prior to study entry, for males not on
                          testosterone replacement therapy.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          initial drug administration Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable
                          antiretroviral regimen for at least 60 days
                          prior to study entry. Allowed: 1. For women:
                          treatment with oral contraceptive agents
                          containing ethinyl estradiol less than 50
                          microg/ml, hormone replacement therapy
                          including Premarin (1.25 mg or less) and
                          other estrogen preparations, or long-acting
                          progestational agents, provided that the
                          patient has been on stable regimens for at
                          least 6 months prior to enrollment. Patients
                          who have discontinued oral contraceptives,
                          hormone replacement, or progestational
                          derivatives must be off such therapy for at
                          least 6 months to be eligible for enrollment.
                          2. For men: treatment with testosterone
                          replacement (FDA-approved fo
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required:
                          Antiretroviral regimen, same as pre-entry,
                          with no intention to change the regimen
                          during the 32-week study. Note: Patients
                          should not change otherwise effective
                          antiretroviral regimens solely on the basis
                          of concerns about metabolic complications.
                          Permitted: 1. Antilipid drugs, including
                          gemfibrozil, cholestyramine, clofibrate,
                          colestipol, and HMG-CoA reductase inhibitors
                          (including atorvastatin, fluvastatin,
                          lovastatin, and pravastatin). 2.
                          Over-the-counter drugs, including chromium
                          picolinate, creatine monohydrate, fish oil
                          (omega-3 fatty acids), GH-releasers
                          (arginine, ornithine, and lysine),
                          beta-hydroxy-beta-methylbutyrate (beta-HMB),
                          alpha-lipoic acid, and shark cartilage. 3.
                          FDA-approved forms of testosterone
                          replacement, including injectable
                          testosterone enanthate, cypionate, or
                          propionate in doses of 400 mg/month or less;
                          testosterone patches designed to deliver 5
                          mg/day; or testosterone gel in prepackaged
                          doses of up to and including 7.5 g/day. 4.
                          Nephrotoxic drugs, provided renal function is
                          monitored.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 65 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: Have
                          been treated for diabetes.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence which, in the
                          opinion of the investigator, would interfere
                          with adherence to study requirements or would
                          endanger the patient's health while on study.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antidiabetic
                          medications, including but not limited to
                          insulin (NPH, regular, lente, and lispro),
                          acetohexamide, chlorpropamide, glimepiride,
                          glipizide, glyburide, tolazamide,
                          tolbutamide, acarbose, metformin,
                          troglitazone, rosiglitazone, and
                          pioglitazone. 2. Estrogen preparations
                          containing greater than 50 microg of ethinyl
                          estradiol or greater than 1.25 mg Premarin
                          per day, or equivalents, within 6 months
                          prior to study entry. 3. Hormonal anabolic
                          therapies including growth hormone,
                          nandrolone, oxandrolone, oxymetholone,
                          stanozolol, supraphysiologic doses of
                          testosterone (greater than 400 mg/month by IM
                          injection or greater than 5 mg/day by
                          transdermal patch), any testosterone creams
                          or analogues, methyltestosterone,
                          fluoxymesterone, over-the-counter products
                          (DHEA and androstenedione), and testosterone
                          gel greater than 7.5 g/day, within 6 months
                          prior to study entry. 4. Appetite stimulants
                          including megestrol acetate, dronabinol, and
                          cyproheptadine, wi
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Concomitant use of ritonavir with simvastatin
                          or lovastatin. 2. Hormonal anabolic therapies
                          including growth hormone, nandrolone,
                          oxandrolone, oxymetholone, stanozolol,
                          supraphysiologic doses of testosterone
                          (greater than 400 mg/month by IM injection or
                          greater than 5 mg/day by transdermal patch),
                          any testosterone creams or analogues,
                          methyltestosterone, fluoxymesterone,
                          over-the-counter products (DHEA and
                          androstenedione), and testosterone gel
                          greater than 7.5 g/day. 3. Other experimental
                          agents designed to improve appetite or weight
                          gain. 4. Appetite stimulants including
                          megestrol acetate, dronabinol, and
                          cyproheptadine. 5. Systemic steroids,
                          including but not limited to glucocorticoid
                          agents, prednisone, methylprednisolone,
                          dexamethasone, and hydrocortisone, at more
                          than physiologic replacement doses (i.e.,
                          greater than 7.5 mg prednisone/day and
                          greater than 30 mg hydrocortisone/day). 6.
                          Immune modulators including interleukin-2
                          (IL-2), interferon
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Patient being
                          treated for diabetes. 2. Allergy or
                          sensitivity to metformin or rosiglitazone. 3.
                          Body mass index (BMI) less than 18 kg/m2 or
                          greater than 40 kg/m2. 4. Diarrhea Grade 2 or
                          greater. 5. Nausea Grade 2 or greater. 6.
                          Vomiting Grade 2 or greater. 7. Significant
                          cardiac disease. Patients with cardiac
                          disease corresponding to the American Heart
                          Association Class I heart disease
                          classification are not eligible. Note:
                          Patients with cardiac disease who do not have
                          undue fatigue, palpitations, or anginal pain
                          after ordinary physical activity and do not
                          have restrictions on ordinary activity are
                          eligible.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0340  Metformin hydrochloride
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0341  Rosiglitazone maleate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arms A and C: 500 mg
                          q12h Weeks 1 & 2, then 1000 mg q12Weeks 3 to
                          16. All Arms (open-label): 500 mg q12h Weeks
                          17 & 18, then 1000 mg Weeks 19 to 32. Drug 2:
                          Arms B and C: 4 mg once daily, Weeks 1 to 16.
                          All Arms (open-label): 4 mg once daily, Weeks
                          17 to 32
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Arms A and C: 1000 mg
                          Weeks 1 & 2, then 2000 mg Weeks 316. All Arms
                          (open-label): 1000 mg Weeks 17 & 18, then
                          2000 mg Weekto 32. Drug 2: Arms B and C: 4
                          mg, Weeks 1 to 16. All Arms (open-label): 4
                          mg, Weeks 17 to 32
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 32 weeks.
OTHER TREATMENT INFO.     END POINT: Change from baseline to Week 16,
                          and subsequent change to Week 32, of: fasting
                          insulin levels; insulin AUC (from OGTT);
                          visceral fat area; safety measures, including
                          laboratory measures of lactate, LFTs,
                          creatinine, glucose, and hemoglobin and
                          symptoms of diarrhea, nausea, and vomiting.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Drug-related
                          toxicity. 2. Requirement for, or use of,
                          prohibited concomitant medications. 3.
                          Pregnancy or breast-feeding. 4. Request by
                          the patient to withdraw. 5. Request by the
                          primary care provider, if it appears that the
                          study is no longer in the best interest of
                          the patient. 6. Clinical reasons believed
                          life-threatening by the physician, even if
                          not addressed in the toxicity management of
                          the protocol. 7. Patient is judged by the
                          investigator to be at significant risk of
                          failing to comply with the provisions of the
                          protocol so as to cause harm to self or
                          seriously interfere with the validity of the
                          study results.
OTHER TREATMENT INFO.     MODIFICATION: Dose reductions are allowed
                          only for metformin or metformin placebo (from
                          1000 mg to 500 mg every 12 hours) per
                          protocol guidelines and not for rosiglitazone
                          or rosiglitazone placebo. A temporary drug
                          hold or permanent drug discontinuation due to
                          a toxicity means that both metformin and
                          rosiglitazone are held or permanently
                          discontinued. Patients are not allowed to
                          discontinue only 1 drug.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 010604.
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] No longer recruiting 010702.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010627.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 010730.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010731.
MISSOURI                  Washington Univ / St Louis Connect Care 4511
                          Forest Park Parkway / Suite 304 Saint Louis,
                          MO 63108 Mike Klebert [phone]
                          Recruiting 010621.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          010621.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010717.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010717.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010731.

31
UNIQUE IDENTIFIER         NIH/01377
PROTOCOL ID NUMBERS       NIAID ACTG A5116
PROTOCOL TITLE            A Phase II, Randomized, Controlled Trial of
                          Two Potent, Simplified Regimens Utilizing a
                          Protease Inhibitor-Sparing Regimen versus a
                          Nucleoside-Sparing Regimen for HIV-Infected
                          Subjects Who Participated in ACTG 388 and
                          Have 200 or Less HIV-1 RNA Copies/ml.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare time to confirmed
                          virologic failure (plasma HIV-1 RNA levels
                          greater than 200 copies/ml in the 2 treatment
                          arms).
GENERAL DESCRIPTION       RATIONALE: ACTG 388 was designed to evaluate
                          2 4-drug regimens compared with a 3-drug
                          regimen in patients who were relatively
                          treatment naive. Based on the increased
                          complexity and toxicity of 4-drug regimens
                          and the resultant negative impact on response
                          as compared with 3-drug regimens, studies
                          evaluating simplified potent regimens appear
                          warranted. This study should allow the
                          achievement of enhanced virologic activity
                          without necessarily increasing the number of
                          antiretroviral drugs and should limit both
                          pill burden and regimen complexity.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either a protease inhibitor
                          (PI)-sparing regimen of 2 nucleoside reverse
                          transcriptase inhibitors (NRTIs) with
                          efavirenz (EFV) (Arm I) or an NRTI-sparing
                          regimen of EFV with lopinavir/ritonavir
                          (LPV/r) (Arm II). Arm I options are
                          enteric-coated didanosine (ddI-EC) plus
                          lamivudine (3TC), ddI-EC plus zidovudine
                          (ZDV), ZDV plus 3TC (or Combivir), stavudine
                          (d4T) plus 3TC, or ddI-EC plus d4T (with
                          exceptions as noted in the protocol). Only
                          LPV/r, EFV, d4T, and ddI are provided by the
                          study; other medications are obtained by
                          prescription. All patients are evaluated for
                          safety and for virologic and immunologic
                          responses at Weeks 4, 8, and then every 8
                          weeks until the study ends. In addition, all
                          patients have assessments for fat
                          redistribution, fasting lipid profiles,
                          fasting insulin levels, venous lactate
                          levels, and adherence. An interim analysis is
                          done for safety. Patients may enroll in
                          A5124s, a Visceral Adipose Tissue Substudy,
                          and A5125s, a Bone Mineral Density Substudy.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 240 patients. Participants
                          of ACTG 388 and the ACTG 388 extension.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks beyond
                          enrollment of the last patient.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 98/240 010731.
PROTOCOL DETAILS          STUDY DURATION: 12 weeks enrollment plus 48
                          weeks beyond enrollment of the last
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 31
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (010306)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG 5116. Substudy
                          AACTG A5124s. Substudy AACTG A5125s
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Be participants in ACTG 388 with a plasma
                          HIV-1 RNA level of 200 or less copies/ml
                          within 70 days prior to entry. 2. Document
                          any menopause, sterilization, and
                          azoospermia. Patient reporting is acceptable.
                          Women not of reproductive potential (those
                          who have reached menopause or undergone
                          hysterectomy, oophorectomy, or tubal
                          ligation) or whose male partner has undergone
                          successful vasectomy with resultant
                          azoospermia or has azoospermia for other
                          reasons are eligible without required
                          contraception. 3. Agree not to try to become
                          pregnant or to impregnate, or to donate
                          sperm, or to participate in in vitro
                          fertilization. 4. Agree to use a combination
                          of 2 approved contraception methods if
                          receiving EFV and for 6 weeks after stopping
                          EFV, or 1 approved contraception method if
                          not receiving EFV. Approved methods include
                          condoms (male or female) with or without a
                          spermicidal agent, diaphragm or cervical cap
                          with spermicide, IUD, and hormonal-based
                          contraception (unless antiretroviral drugs
                          interfere with the metabolism of
                          hormonal-based contraceptives. If this is the
                          case, hormonal-based contraceptives are not
                          sufficient as the sole contraception method).
                          5. Have written consent of parent/legal
                          guardian if under 18 years of age.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          initial drug administration Not pregnant
                          Abstinence or effective (approved) method of
                          birth control.
PATIENT INCLUSION CRIT.   OTHER: Included: Prisoners, with local
                          institutional review board decision.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Stable
                          antiretroviral therapy without a clinically
                          significant drug-related toxicity or
                          intercurrent illness at the time of study
                          entry. Allowed: 1. Medications for the
                          treatment, maintenance, and/or
                          chemoprophylaxis of opportunistic infections
                          as medically indicated, unless excluded in
                          the protocol. 2. Antibiotics as medically
                          indicated, unless excluded in the protocol.
                          3. Antifungal drugs as medically indicated,
                          unless excluded in the protocol. 4. Antiviral
                          drugs, other than antiretroviral drugs, as
                          medically indicated, unless excluded in the
                          protocol. 5. Systemic corticosteroids as
                          medically indicated, for short courses (21
                          days or less). Chronic systemic
                          corticosteroid use is permitted only if
                          physiological replacement dosages are used
                          and approved by the protocol chair/co-chairs.
                          6. Recombinant erythropoietin, granulocyte
                          colony-stimulating factor, and
                          granulocyte-macrophage colony-stimulating
                          factor as medically indicated. 7. Regularly
                          prescribed medications such as antipyretics,
                          antiemetics, antidiarrheals, analgesics,
                          allergy medications, antidepressants, sleep
                          medications, oral contraceptives, megestrol
                          acetate, testosterone and related products,
                          or others as medically indicated, unless
                          excluded in the protocol. 8. Expanded access
                          drugs in salvage therapy regimens, with
                          approval by the protocol chair/co-chairs.
                          Allowed, with caution: 1. Interferon, at
                          doses below 10 MIU/week, with approval by the
                          protocol chair/co-chairs. 2. Rifabutin, at 75
                          percent of the recommended dose of 300 mg
                          daily when given with LPV/r. A maximum dose
                          of 150 mg every other day or 3 times per week
                          is recommended. 3. Rifabutin, when
                          coadministered with EFV 2 to 3 times per
                          week, should be increased to 450 mg. Note:
                          There are no data for dosing rifabutin when
                          combined with both LPV/r and EFV. Prior to
                          the use of rifabutin in patients taking both
                          LPV/r and EFV, contact the protocol
                          chair/co-chairs. 4. Sildenafil should not
                          exceed a maximum single dose of 25 mg in a
                          48-hour period when used in combinatio
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Phenotypic or genotypic viral resistance to
                          ZDV, d4T, ddI, EFV, nevirapine, delavirdine,
                          indinavir, nelfinavir, saquinavir, or
                          ritonavir, while on ACTG 388 study treatment.
                          Note: Less than 10-fold phenotypic resistance
                          to NNRTIs in patients who have not received
                          NNRTIs will not be a criterion for exclusion.
                          Two or fewer separate mutations at the
                          protease codons 10, 20, 23, 32, 36, 54, 71,
                          73, or 77 will not be a criterion for
                          exclusion. 2. Allergy/sensitivity to study
                          drugs or their formulations.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Use of
                          the following: antiarrhythmics (flecainide or
                          propafenone), antihistamines (astemizole or
                          terfenadine), antimycobacterial agents
                          (rifampin), ergot derivatives
                          (dihydroergotamine, ergonovine, ergotamine,
                          or methylergonovine), GI motility agents
                          (cisapride), herbal products (St. John's wort
                          [Hypericum perforatum]), HMG-CoA reductase
                          inhibitors (lovastatin or simvastatin),
                          neuroleptics (pimozide), and
                          sedatives/hypnotics (midazolam and
                          triazolam). 2. Antiretroviral therapies,
                          other than study medication regimens as
                          outlined in the protocol, unless approved by
                          the protocol chair/co-chairs. 3.
                          Investigational drugs, except as outlined for
                          salvage therapy, unless approved by the
                          protocol chair/co-chairs. 4. Systemic therapy
                          for a malignancy unless approved by the
                          protocol chair/co-chairs.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0316  Lopinavir/Ritonavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0269  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0016  Didanosine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm II: LPV/r, 533
                          mg/133mg bid. Drug 2: 600 mg qd. Drug 3: Arm
                          I (according to option selected): 40 mg (30
                          mg if lthan 60 kg) bid. Drug 4: Arm I
                          (according to option selected): 400 mg (250
                          mg ifthan 60 kg) qd
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: LPV/r, 1066mg/266 mg.
                          Drug 2: 600 mg. Drug 3: 80 mg (60 mg if less
                          than 60 kg). Drug 4: 400 mg (250 mg if less
                          than 60 kg)
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral, tablets or
                          enteric-coated capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks beyond
                          enrollment of the last patient.
OTHER TREATMENT INFO.     END POINT: Virologic: time to a confirmed
                          plasma HIV-1 RNA measurement greater than 200
                          copies/ml.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Drug-related
                          toxicity. 2. Requirement for prohibited
                          concomitant medications. 3. Breast-feeding or
                          pregnancy. 4. Patient's request. 5. Primary
                          care provider's request, if he/she thinks the
                          study is no longer in the best interest of
                          the patient. 6. Clinical reasons believed
                          life threatening by the physician, even if
                          not addressed in the toxicity management of
                          the protocol. 7. Significant risk to patient,
                          in the investigator's judgment, due to
                          failure to comply with the protocol so as to
                          cause harm to the patient or to interfere
                          with the validity of the study results. 8.
                          Discretion of the AACTG, FDA, NIAID,
                          investigator, or pharmaceutical sponsor.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010621.
COLORADO                  Denver Dept of Health and Hosps 4200 East 9th
                          Ave / Campus Box B-196 Denver, CO 80262 M
                          Graham Ray [phone] No longer recruiting
                          010702.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010702.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010618.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Ericka Patrick [phone] Recruiting
                          010618.
HAWAII                    Queens Med Ctr Leahi Hospital / Young
                          Building / 3675 Kilauea Ave Honolulu, HI
                          96816 Debra Ogata-Arakaki [phone]
                          Recruiting 010618.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010621.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 010621.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010618.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010618.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010712.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010712.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010712.
LOUISIANA                 Charity Hosp / Tulane Univ Med School 1430
                          Tulane Ave SL-87 New Orleans, LA 70112 Mike
                          Foster [phone] Recruiting 010628.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 010702.
MISSOURI                  Washington Univ / St Louis Connect Care 4511
                          Forest Park Parkway / Suite 304 Saint Louis,
                          MO 63108 Mike Klebert [phone]
                          Recruiting 010618.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          010618.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010618.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 010627.
NEBRASKA                  Univ of Nebraska Med Ctr 985130 Nebraska Med
                          Ctr Omaha, NE 681985130 Frances Van Meter
                          [phone] Recruiting 010621.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010618.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Rachele Cruz
                          [phone] Recruiting 010618.
NEW YORK                  Cornell Clinical Trials Unit 119 West 24th St
                          / Ground Floor New York, NY 10011 Todd
                          Stroberg [phone] Recruiting 010618.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010730.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Valery Hughes [phone]
                          Recruiting 010618.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010618.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010618.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 010618.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 010731.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] Recruiting 010731.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010621.

32
UNIQUE IDENTIFIER         NIH/01375
PROTOCOL ID NUMBERS       NIAID ACTG P1012
PROTOCOL TITLE            A Phase I Pharmacokinetic Study of Once
                          Versus Twice Daily Dosing With Zidovudine and
                          Lamivudine.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare the steady-state predose
                          amounts of ZDV-triphosphate (ZDV-TP) and
                          3TC-triphosphate (3TC-TP) in peripheral blood
                          mononuclear cells (PBMCs) when the same total
                          daily dose of zidovudine (ZDV) and lamivudine
                          (3TC), administered as the commercially
                          available combination product Combivir, is
                          administered once versus twice daily. To
                          describe the kinetics of phosphorylation of
                          ZDV and 3TC mono-, di-, and triphosphates in
                          PBMCs over 24 hours at steady state when
                          Combivir is administered as a single daily
                          dose.
GENERAL DESCRIPTION       RATIONALE: Initial dosing regimens of ZDV
                          were based on the plasma half-life of the
                          drug. However, recent studies of the
                          intracellular metabolism of ZDV have
                          demonstrated that the active anabolite,
                          ZDV-TP, is present within the cell for an
                          extended period of time relative to the drug
                          in the plasma. This suggests that antiviral
                          activity may be present for a sufficient time
                          frame with less-frequent dosing of the drug.
                          Careful comparison of the rate and extent of
                          intracellular phosphorylated ZDV metabolites
                          as a function of schedule will determine
                          whether less-frequent dosing has a sound
                          pharmacological basis. Also, the
                          intracellular metabolism of 3TC is via
                          different enzymes than that of ZDV and there
                          are quantitative differences in the amount of
                          triphosphate formed from both drugs. This
                          study will provide information about
                          intracellular metabolites when both ZDV and
                          3TC are concurrently administered.
GENERAL DESCRIPTION       METHODOLOGY: This is a study of 2 schedules
                          of Combivir therapy. At study entry or Part
                          I, all patients take Combivir twice daily for
                          the 7-day adherence assessment. Patients who
                          have demonstrated 70 percent or greater
                          adherence [AS PER AMENDMENT 7/20/01: 70
                          percent compliance with the study regimen for
                          Combivir. This corresponds to taking at least
                          10 of the prescribed 14 Combivir tablets
                          during the 7 days prior to an adherence
                          assessment, including all scheduled doses in
                          the 24-hour period prior to that
                          assessment.], and have taken all scheduled
                          Combivir doses in the previous 24 hours, have
                          pharmacokinetic samples obtained and are
                          randomized to Group A or Group B in Part II.
                          Group A patients take 2 Combivir tablets once
                          daily; Group B patients take 1 Combivir
                          tablet twice daily. After patients have
                          completed the targeted duration of Part II (7
                          days for Group A and 7-14 days for Group B),
                          they are assessed for adherence. Patients who
                          have demonstrated 70 percent or greater
                          adherence, and have taken all scheduled
                          Combivir doses in the previous 24 hours, have
                          pharmacokinetic samples obtained and then
                          change to the alternate dosing schedule.
                          Group A patients take 1 Combivir tablet twice
                          daily; Group B patients take 2 Combivir
                          tablets once daily. After patients have
                          completed the targeted duration of Part III
                          (7-14 days for Group A and 7 days for Group
                          B), they are assessed for adherence. All
                          patients who meet the adherence criteria have
                          pharmacokinetic samples obtained. After
                          completion of Part III pharmacokinetic
                          studies, patients have completed the study.
                          (Note: Combivir will not be provided in this
                          study.).
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug dosing schedule,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients. Fifteen
                          patients are accrued initially for each of 2
                          groups. Patients who are enrolled but fail
                          the Day 7 (Part I) or subsequent (Part II
PROTOCOL DETAILS          ACTUAL ACCRUAL: 7/20 010731.
PROTOCOL DETAILS          STUDY DURATION: The study will continue until
                          evaluable information is obtained
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010720)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1012
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Cross-Over Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. A confirmed diagnosis of HIV-1
                          infection defined as 2 positive assays from 2
                          different samples. The 2 results may be in
                          any combination of the following: 1) at any
                          age: DNA PCR, RNA PCR, HIV culture, or
                          licensed ELISA with confirmatory Western
                          blot; and 2) over 4 weeks of age: p24 antigen
                          detection. 2. CD4 cell count greater than 250
                          cells/microL. 3. Consent of a parent or
                          guardian if under 18 years of age.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 250 cells/microL.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test Abstinence
                          or agree to use both a barrier and a second
                          method of birth control / contraception
                          during the study.
PATIENT INCLUSION CRIT.   WEIGHT: Included: Weight greater than 40 kg.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Documented
                          history of at least 4 weeks of therapy with a
                          three-drug or greater regimen that must
                          include ZDV and 3TC (as individual drugs or
                          Combivir) and at a minimum a protease
                          inhibitor or a nonnucleoside reverse
                          transcriptase inhibitor, with no intention to
                          change any component of the pre-entry
                          antiretroviral regimen during the course of
                          the study.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: All
                          components of the pre-entry antiretroviral
                          regimen, including commercially available
                          protease inhibitors and nonnucleoside reverse
                          transcriptase inhibitors, including
                          efavirenz. The protocol chair must approve
                          changes or additions to the pre-entry
                          regimen.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 12
                          years less than or equal to 24 years.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Chemotherapy for active malignancy. 2.
                          Nucleoside or nucleotide reverse
                          transcriptase inhibitors, other than ZDV and
                          3TC, and hydroxyurea.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Current Grade 3
                          or 4 laboratory toxicity as defined by the
                          Division of AIDS (DAIDS) Toxicity Table for
                          Grading Severity of Pediatric (greater than 3
                          months of age) Adverse Experiences. 2.
                          Presence of an acute opportunistic or
                          bacterial infection requiring therapy at the
                          time of enrollment. 3. Any clinically
                          significant diseases (other than HIV
                          infection) or clinically significant findings
                          during the screening medical history or
                          physical examination that, in the
                          investigator's opinion, would compromise the
                          outcome of this study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0285  Lamivudine/Zidovudine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Part I, All
                          patients: 1 tablet (ZDV 300 mg/3TC 150 mg) 7
                          days. Part II, Group A: 2 tablets qd x 7
                          days. Part II, Group B: 1 tablet bid x 7-14
                          days. Part III, Group A: 1 tablet bid x 7-14
                          days. Part III, Group B: 2 tablets qd x 7
                          days
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: ZDV 600 mg/3TC 300 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     END POINT: 1. Ratios of trough concentration
                          measures of ZDV-TP and 3TC-TP in PBMCs from
                          the twice-daily regimen to the corresponding
                          measures from the once-daily regimen. 2.
                          Pharmacokinetic parameters for once-daily
                          dosing.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. The patient or
                          legal guardian refuses further treatment
                          and/or follow-up evaluations. 2. The
                          investigator determines that further
                          participation would be detrimental to the
                          patient's health or well-being. 3. The
                          patient fails to comply with scheduled study
                          evaluations or to meet adherence criteria. 4.
                          The patient becomes pregnant. 5. The patient
                          requires a treatment not allowed on the
                          study.
OTHER TREATMENT INFO.     MODIFICATION: At the end of Part I, if less
                          than 70 percent adherence is demonstrated,
                          the patient will be taken off study and will
                          have no further assessments performed. At the
                          end of Part II and/or Part III, if less than
                          70 percent adherence is demonstrated,
                          patients are counseled about the importance
                          of medication adherence. Patients receiving
                          the once-daily regimen are placed on a
                          twice-daily regimen while barriers to
                          adherence are addressed. If patients and site
                          investigators agree to continue the study,
                          patients resume the once-daily regimen for 7
                          days. Patients receiving the twice-daily
                          regimen continue on this regimen for an
                          additional 7-14 days while barriers to
                          adherence are addressed. In all cases, if
                          patients are unable to reach the required 70
                          percent adherence after a second try or if
                          the scheduled evaluations are beyond 21 days,
                          the protocol chair should be contacted.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 010605.
NEW JERSEY                St Joseph's Hosp & Med Center 703 Main St
                          Paterson, NJ 07503 Anne Townley [phone]
                          Recruiting 010705.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 010522.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Sylvia Davila Nieves [phone] Recruiting
                          010521.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Jill Utech [phone] Recruiting
                          010605.

33
UNIQUE IDENTIFIER         NIH/01374
PROTOCOL ID NUMBERS       NIAID ACTG A5113
PROTOCOL TITLE            A Study of Immune Function in Healthy Adults
                          Aged 18-30 and 45 and Older.
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare baseline differences in
                          total numbers and percentages of naive CD4+
                          (CD45RA+/CD62L+) lymphocytes between healthy,
                          HIV-seronegative volunteers and
                          HIV-seropositive participants of study A5015.
GENERAL DESCRIPTION       RATIONALE: Aging is associated with declines
                          in both cellular and humoral immunity. A
                          consistent observation of the aging immune
                          system is a change in T cells. Another
                          possible mechanism of diminished cellular
                          immunity associated with age includes
                          accelerated lymphocyte apoptosis. Enhanced
                          lymphocyte apoptosis may play an important
                          role in the pathogenesis of HIV disease. This
                          study will use healthy volunteers to confirm
                          and expand upon such observations. Samples
                          from these volunteers will serve as controls
                          to those from the HIV-infected participants
                          of A5015 (a comparison study of 2
                          age-differentiated cohorts to determine
                          potential mechanisms that might contribute to
                          accelerated HIV-disease progression that is
                          associated with aging).
GENERAL DESCRIPTION       METHODOLOGY: This is a non-treatment study;
                          however, volunteers receive hepatitis A and
                          tetanus vaccinations. Numbers of
                          phenotypically naive CD4+ cells
                          (CD45RA+/CD62L+) are compared between
                          healthy, HIV-seronegative volunteers and
                          HIV-seropositive patients of A5015. An array
                          of assays to assess baseline differences in
                          immune function between these study
                          populations are performed. Expression of
                          markers of activation are compared by
                          measuring the coexpression of HLA-DR+/CD38+
                          and CD28+ on CD4+ and CD8+ lymphocytes
                          between these populations. To investigate
                          possible age-associated differences in
                          apoptosis, Fas (CD95+) expression is measured
                          on CD4+ and CD8+ T cells by flow cytometry,
                          and spontaneous apoptosis is assessed using
                          the propidium iodide method. DTH
                          hypersensitivity to skin test antigens,
                          lymphocyte proliferation to mitogens, soluble
                          antigens, recall antigens, and neoantigens
                          are compared between the 2 populations.
                          Antibody responses to vaccination with
                          tetanus and hepatitis A are assessed.
                          Finally, thymic size as measured by CT scan
                          and the frequency of T cells that contain
                          TRECs is compared between these 2
                          populations.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Immunology, Natural history.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 48 patients. 24 patients
                          per age cohort.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 40/48 010717.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (010305)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Seronegativity.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5113
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must:
                          1. Be willing to undergo HIV testing. 2. Be
                          between the ages of 18 and 30 or 45 or older.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >=9.1 gm/dl for men; >= 8.9 gm/dl
                          for women.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase <= 1.5 x ULN. If serum
                          amylase is > 1.5 x ULN, then fractionate for
                          pancreatic amylase, which must be <= 1.5 x
                          ULN.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test within 30
                          days of study entry.
PATIENT INCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 6 months prior to study entry.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Volunteers with
                          the following prior conditions are excluded:
                          1. Cancer or malignancy. 2. HIV-1 infection
                          as documented by any licensed ELISA test kit
                          performed within 30 days of study entry and
                          confirmed by Western blot by any laboratory
                          certified for these assays. 3. Serious
                          infection or other serious medical illness
                          that is potentially life threatening and
                          requires systemic therapy and/or
                          hospitalization within 90 days prior to study
                          entry. 4. Anaphylaxis or severe local
                          reaction to tetanus vaccine at any time in
                          the past.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Within 6
                          months prior to study entry: systemic
                          corticosteroids; systemic cytotoxic
                          chemotherapy; erythropoietin, granulocyte
                          colony-stimulating factor (G-CSF),
                          granulocyte-macrophage colony-stimulating
                          factor (GM-CSF), or growth hormone; any
                          immunomodulator including thalidomide,
                          interleukins, interferons, or other
                          cytokines; anabolic steroids, unless within
                          physiological replacement levels; and any
                          investigational agent, unless allowed
                          otherwise by the protocol chair. 2. Tetanus
                          toxoid within 5 years prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          corticosteroids. 2. Systemic cytotoxic
                          chemotherapy. 3. Erythropoietin, G-CSF,
                          GM-CSF, or growth hormone. 4. Any
                          immunomodulator including thalidomide,
                          interleukins, interferons, or other
                          cytokines. 5. Anabolic steroids, unless
                          within physiological replacement levels. 6.
                          Any investigational agent, unless allowed
                          otherwise by the protocol chair.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: Immunity to
                          hepatitis A as determined by presence of
                          hepatitis A antibody (Hep A tot).
OTHER TREATMENT INFO.     END POINT: Total numbers and percentages of
                          naive CD4+ (CD45RA+/CD62L+) lymphocytes.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010517.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010627.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010731.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 010612.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010605.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          010621.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone]
                          Recruiting 010517.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010731.

34
UNIQUE IDENTIFIER         FDA/01373
PROTOCOL ID NUMBERS       FDA 317A
PROTOCOL TITLE            A Randomized, Parallel Group, Double-Blind,
                          Placebo-Controlled, Dose-Ranging, Multicenter
                          Study of Recombinant Human Growth Hormone
                          (Serostim) in the Treatment of HIV-Associated
                          Catabolism/Wasting.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine the change in physical
                          function at Week 12 for patients receiving
                          full-dose somatropin compared to patients
                          receiving placebo. To determine the change in
                          lean body mass at Week 12 for patients
                          receiving somatropin full- or half-dose
                          compared to patients receiving placebo.
                          Methodology: Patients are selected randomly
                          to receive full-dose somatropin, half-dose
                          somatropin, or placebo. Clinical assessments
                          are taken at Week 12. Patients who reach the
                          primary study endpoint will be eligible for a
                          12-week ancillary course of somatropin
                          treatment at the full dose.
GENERAL DESCRIPTION       METHODOLOGY: Patients are selected randomly
                          to receive full-dose somatropin, half-dose
                          somatropin, or placebo. Clinical assessments
                          are taken at Week 12. Patients who reach the
                          primary study endpoint will be eligible for a
                          12-week ancillary course of somatropin
                          treatment at the full dose.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010315)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 732 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 28 weeks
                          maximum.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/732.
PROTOCOL DETAILS          DISEASE STUDIED: HIV Wasting Syndrome.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: GF9037
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Open Label;
                          Placebo-Controlled Trial; Random Allocation;
                          Parallel Designs; Dose-Response Design;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Clearly documented HIV infection. 2.
                          Evidence of HIV/AIDS wasting or cachexia
                          (loss of body weight, lean body mass, body
                          cell mass). 3. Ability to meet specific
                          treatment, medication, and nutrition
                          requirements.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required:
                          Anti-retroviral therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0327  Somatropin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Full dose:
                          approximately 0.1 mg/kg/day once daily in
                          thevening. Half dose: approximately 0.1
                          mg/kg/day once daily on alternat
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Maximum 6 mg depending
                          on body weight
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Injection
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: The primary endpoint will be the
                          change in physical function at Week 12,
                          comparing somatropin at full dose to placebo.
                          The secondary dose-finding endpoint will be
                          the change in lean body mass at Week 12,
                          comparing full dose and half dose to placebo.
SUPPORTING AGENCY         Serono Laboratories Inc.
LAST REVISION DATE        20010315

35
UNIQUE IDENTIFIER         NIH/01372
PROTOCOL ID NUMBERS       NIAID ACTG P1024
PROTOCOL TITLE            Evaluation of the Immunogenicity of
                          Pneumococcal Conjugate Vaccine and Routine
                          Pediatric Immunizations in HIV-Infected
                          Children Treated with Highly Active
                          Antiretroviral Therapy (HAART).
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          short-term immunogenicity of 2 doses of
                          Pneumococcal Conjugate Vaccine (PCV) followed
                          by 1 dose of Pneumococcal Polysaccharide
                          Vaccine (PPV) in HIV-infected children on
                          highly active antiretroviral therapy (HAART).
                          To determine whether HIV-infected children on
                          HAART have protective levels of antibody at
                          study entry to previously administered
                          measles vaccine. To determine whether
                          HIV-infected children on HAART respond to
                          booster immunization with measles vaccine.
GENERAL DESCRIPTION       RATIONALE: Infection by Streptococcus
                          pneumoniae is the most frequent opportunistic
                          infection observed in HIV-infected children.
                          PCVs are immunogenic and efficacious in
                          normal children and offer hope of reducing
                          pneumococcal infections in HIV-infected
                          children. The degree to which children on
                          HAART are protected by prior immunizations
                          and are responsive to new immunizations is
                          still largely undefined. This study is
                          designed to answer whether PCV immunizations
                          are safe and effective. The immune responses
                          to prior immunizations and responsiveness to
                          booster doses of vaccines against measles,
                          pertussis, and hepatitis B virus of children
                          on HAART will also be examined. Answers to
                          these questions will determine whether these
                          children are likely to be protected against
                          these clinically relevant pathogens and
                          whether they should routinely receive booster
                          doses of these vaccines after a period of
                          HAART.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified on the
                          basis of CD4 percentage and age. Patients
                          that previously received a primary hepatitis
                          B vaccine (HBV) series receive an HBV
                          immunization at entry. Other vaccinations may
                          be given (based on age and/or CD4 cell
                          measurements, and immunization status) for
                          PCV at entry and 2 months, and
                          measles-mumps-rubella (MMR) vaccine and PPV
                          at 4 months. Some patients may be
                          administered DTaP at a 6-month visit on the
                          basis of age, previous immunization history,
                          and negative tetanus antibody status.
                          Follow-up visits are done at 8, 12, and 24
                          months. Blood samples are collected at all
                          clinic visits for assessment of HIV RNA,
                          immune responses against pneumococcus,
                          measles, pertussis, and hepatitis B virus,
                          and for laboratory evaluations.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Immunology, Vaccine
                          prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 300 patients. 75 patients
                          in each of 4 stratified groups (68 evaluable
                          patients are required in each group for
                          analysis).
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 44/300 010731.
PROTOCOL DETAILS          STUDY DURATION: 24 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 24
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010430)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 1024
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have perinatal HIV infection, defined as
                          acquisition of HIV from mother before or
                          during birth. 2. Have HIV infection, defined
                          as 2 positive test results obtained on 2
                          different days from 2 different samples. The
                          2 tests can be any combination of the
                          following: HIV-antibody (ELISA + WB),
                          obtained at age greater than 18 months;
                          HIV-culture, any age; HIV-DNA PCR at any age;
                          HIV-RNA PCR (copy number greater than 10,000
                          copies/ml), at any age; or neutralizable HIV
                          p24 antigen obtained at greater than 28 days
                          of age. 3. Have a HIV RNA PCR of less than
                          30,000 copies/ml by Roche Amplicor Assay
                          within 30 days of study entry. 4. Expect to
                          be able to complete all study immunizations
                          and evaluations. 5. Have consent of parent or
                          guardian if under 18 years of age.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl Within 30 days of study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 cells/mm3 Within 30
                          days of study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN ULN (Upper Limit of
                          Normal), for total bilirubin. Within 30 days
                          of study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN Within 30 days of study
                          entry.
PATIENT INCLUSION CRIT.   CREATININE: Serum creatinine < 1.5 mg/dl if
                          under 12 years of age; < 2.5 mg/dl if 12 to
                          18 years of age. Within 30 days of study
                          entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Not pregnant
                          Negative pregnancy test within 7 days of
                          study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: 1. Have been on
                          current HAART regimen for 6 months or more.
                          HAART is defined as 3 or more antiretrovirals
                          (from at least 2 of the available therapeutic
                          classes, i.e., NRTI, NNRTI, or PI). No
                          impending changes to the current HAART
                          regimen should be anticipated at the time of
                          study entry. 2. Previous receipt of 4 or more
                          doses of DTP or DTaP vaccine documented by
                          review of written medical records or
                          immunization card. 3. Previous receipt of 1
                          or more doses of MMR vaccine (unless
                          contraindicated by CD4 percent [AS PER
                          AMENDMENT 4/30/01: or CD4 number]) documented
                          by review of written medical records or
                          immunization card. Required for HBV study:
                          Previous receipt of an
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. G-CSF and
                          erythropoietin. 2. Non-steroidal
                          anti-inflammatory agents and inhaled
                          corticosteroids.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 02
                          years less than or equal to 18 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Pre-HAART nadir CD4 of 25 percent or higher
                          and CD4 at study screening below 25 percent.
                          2. Pre-HAART nadir CD4 of 15 to less than 25
                          percent and CD4 at study screening below 15
                          percent. 3. Previous Grade 3 or higher
                          adverse reaction to PPV. 4. Previous allergic
                          reaction to any MMR, HBV, or PPV vaccines or
                          to constituents of these vaccines. 5.
                          Previous allergic reaction to any DTP, DTaP,
                          DT, or dT if 13 years old or younger. 6.
                          Presence of malignancy within 3 months of
                          study screening or treatment for malignancy
                          within 3 months of study entry. 7.
                          Co-enrollment in studies of any of the
                          vaccines used in this study or in studies
                          including immunomodulatory therapy.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Immune globulin
                          products, platelets, or plasma products
                          within the previous 6 months.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Any immune
                          globulin, platelet, and plasma products
                          administered within 6 months preceding each
                          vaccine visit.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Receipt of any
                          killed vaccine within the 4 weeks or any live
                          vaccine within the 6 weeks preceding study
                          entry. 2. Receipt of any PCV. 3. Receipt of
                          any PPV within the previous 6 months.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Immunomodulatory therapy, including IL-2, any
                          interferon product, GM-CSF, or thalidomide
                          during the initial 8 months on study. G-CSF
                          and erythropoietin are allowed. 2. Treatment
                          for malignancy. 3. Immunosuppressive therapy
                          during the initial 8 months on study,
                          including the equivalent of 1 or more
                          mg/kg/day of prednisone in the 2 weeks
                          preceding study screening. 4. Corticosteroids
                          (equivalent of 1 mg/kg/day or more of
                          prednisone) in the 2 weeks preceding each
                          vaccine visit or for 14 or more consecutive
                          days during the initial 8 months on study.
                          Inhaled corticosteroids are allowed. 5. Live
                          vaccines 6 weeks before to 4 weeks after each
                          vaccine visit. 6. Killed vaccines 4 weeks
                          before to 2 weeks after each vaccine visit.
                          7. Any interferon product during the initial
                          8 months on study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. An underlying
                          condition that contraindicates use of any of
                          the study vaccines except for HIV infection
                          with CD4 level below 15 percent, which
                          contraindicates MMR administration. 2. Other
                          known or suspected diseases of the immune
                          system. 3. Acute or chronic medical or
                          surgical conditions or contraindications that
                          in the opinion of the investigator may
                          interfere with the evaluation of the protocol
                          objectives. Note: Previous or current acute
                          or chronic HBV infection excludes patients
                          from the HBV immunogenicity study portion but
                          does not exclude participation in the rest of
                          the study. 4. A known bleeding diathesis. 5.
                          Grade 2 or higher clinical toxicity at
                          screening per Appendix II of the protocol,
                          Supplemental Toxicity Table entitled Vaccine
                          Related Toxicities and Timetable for
                          Reactions. (Note: This is not the DAIDS
                          Standardized Toxicity Table for Grading
                          Severity of Pediatric Adverse Experiences.)
                          6. Patients for whom long-term corticosteroid
                          therapy (of 2 weeks or more) is anticipated.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0240  Pneumococcal Conjugate
                          Vaccine, Heptavalent
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0239  Pneumococcal Vaccine,
                          Polyvalent (23-valent)
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0324  Diphtheria & Tetanus
                          Toxoids &
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 0.5 ml at entry and
                          at Month 2. Drug 2: 0.5 ml at Month 4. Drug
                          3: 0.5 ml at Month 6
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Intramuscular. Drug 3: Intramuscular
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 months.
OTHER TREATMENT INFO.     END POINT: 1. Safety. 2. Immunogenicity. 3.
                          Identification of factors that correlate with
                          response to PCV; PPV; previous measles,
                          pertussis and HBV immunization; and measles,
                          pertussis, and HBV vaccine boosters.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued,
                          but may continue scheduled study-dictated
                          evaluations, for the following reasons: 1.
                          Failure of a Grade 2 or higher clinical
                          toxicity (as defined in the protocol) to
                          resolve to Grade 1 or less, or of a study
                          laboratory toxicity to resolve to the
                          acceptable threshold values defined in the
                          protocol within 3 months of toxicity onset.
                          2. Requirement for disallowed medications or
                          other therapies. 3. Postponement of a vaccine
                          for more than 2 months due to corticosteroid
                          use. 4. Pregnancy. 5. Not on a HAART regimen
                          for a cumulative total exceeding 28 days
                          during the initial 8 months on the study. 6.
                          Investigator's determination that receipt of
                          additional study immunizations would be
                          detrimental to the patient's health or
                          well-being. Patients may be discontinued from
                          further participation in the study for the
                          following: 1. Refusal of further treatment
                          and/or follow-up by patient or legal
                          guardian. 2. Failure of the patient/guardian
                          to comply with study requirements so as to
                          cause harm to the patient or seriously
                          interfere with the validity of the study
                          results. 3. Investigator's determination that
                          further participation would be detrimental to
                          the patient's health or well-being.
OTHER TREATMENT INFO.     MODIFICATION: [AS PER AMENDMENT 4/30/01:
                          Vaccine administration may be temporarily
                          suspended for toxicity, in accordance with
                          the protocol.].
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233 Terry
                          Byars [phone] Recruiting 010605.
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 010702.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Mary Caffery [phone]
                          Recruiting 010730.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 010717.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Patricia Bryan [phone] Recruiting
                          010717.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 010712.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          010612.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 010605.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          010621.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699
                          Margaret Cowie [phone] Recruiting
                          010702.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Kirk
                          Bertelsen [phone] Recruiting 010605.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 010621.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 010621.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 010621.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 010605.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Caroline Nubel [phone] Recruiting
                          010723.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010702.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 010712.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 010730.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 010731.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Sylvia Davila Nieves [phone] Recruiting
                          010712.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 010712.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          010605.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 010605.

36
UNIQUE IDENTIFIER         NIH/01371
PROTOCOL ID NUMBERS       CC 01 C-0067
PROTOCOL TITLE            A Phase II Study of Liposomal Doxorubicin and
                          Interleukin-12 in AIDS-Associated Kaposi's
                          Sarcoma Followed by Chronic Administration of
                          Interleukin-12.
TRIAL CATEGORY            AIDS-Related Malignancies
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine whether the combination
                          of interleukin-12 (IL-12) and liposomal
                          doxorubicin in patients with advanced
                          Kaposi's sarcoma (KS) is able to result in an
                          overall response rate (PR plus CR) which is
                          potentially better than the current estimate
                          of 59 percent for the best published single
                          agent liposomal doxorubicin result in this
                          patient population.
GENERAL DESCRIPTION       RATIONALE:
GENERAL DESCRIPTION       METHODOLOGY: Patients receive 6 3-week cycles
                          of liposomal doxorubicin and IL-12. Inpatient
                          treatment is given for 1 night of the first
                          cycle. Patients are outpatients for all other
                          treatment. At the end of the cycles, chronic
                          twice-weekly administration of IL-12 begins,
                          lasting up to 3 years. Information regarding
                          efficacy and toxicity of the combination will
                          be obtained. Duration of response will also
                          be assessed.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug toxicity.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately 3
                          years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (010125)
PROTOCOL DETAILS          DISEASE STUDIED: Sarcoma, Kaposi.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: 01-C-0067. MB 4010
                          Doxil / IL12
PROTOCOL DETAILS          STUDY DESIGN: Cohort Study
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have Tanner stage greater than or equal to 4
                          if less than 18 years of age. 2. Have HIV
                          seropositivity. 3. Have KS diagnosis
                          confirmed by DCS pathology. 4. Have evaluable
                          KS involving the skin and/or viscera: 1) if
                          KS is restricted to the skin there must be at
                          least 5 KS lesions that are evaluable by
                          non-invasive methods that have not been
                          treated with local therapeutic modalities; 2)
                          pulmonary KS evaluable by CT scanning; or 3)
                          gastrointestinal KS evaluable by direct
                          visualization or fiberoptic instrumentation.
                          5. Have at least 1 of the following
                          indications for cytotoxic chemotherapy:
                          pulmonary involvement, visceral involvement,
                          pain, edema, ulcerating lesions, decreased
                          range of joint motion due to KS, multiple
                          lesions not amenable to local therapy, and
                          significant psychological impact leading to
                          social withdrawal. 6. Have KS that has
                          worsened in the 3 weeks prior to protocol
                          evaluation on a stable regimen of highly
                          active antiretroviral therapy that the
                          patient has been taking for greater than or
                          equal to 4 weeks. 7. Have need of urgent
                          chemotherapy as indicated by, but not limited
                          to, the following: symptomatic pulmonary or
                          other visceral KS, lymphedema that impairs
                          mobility or range of motion, and ulcerating
                          KS lesions. 8. Life expectancy of greater
                          than 2 months (with standard therapy).
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl Within 1 month prior to
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 cells/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3.8 mg/dl With direct fraction
                          <= 0.3 mg/dl and indirect fraction of <= 3.5
                          mg/dl in patients for whom these
                          abnormalities are felt to be due to protease
                          inhibitor therapy.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 30.
PATIENT INCLUSION CRIT.   OTHER: Ejection fraction >= 40 percent, as
                          assessed by MUGA scan or echocardiography,
                          with assessment only if clinically indicated.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 60 days after Not pregnant.
PATIENT INCLUSION CRIT.   OTHER: Excluded: None.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Replacement
                          glucocorticoid therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Hepatic cirrhosis. 2. Inflammatory bowel
                          disease. 3. Malignant tumors other than KS
                          unless: 1) in a complete remission for
                          greater than or equal to 1 year from the time
                          a response was first documented; 2)
                          completely resected basal cell carcinoma; or
                          3) in situ squamous cell carcinoma of the
                          cervix or anus. 4. Evidence of a severe or
                          life-threatening infection within 2 weeks of
                          entry onto the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any
                          chemotherapy cycle within 21 days prior to
                          enrollment (6 weeks for mitomycin C or
                          nitrosoureas). 2. Concomitant use of IL-12
                          and liposomal doxorubicin. 3. Suramin within
                          the last 6 months. 4. Cytokines or bone
                          marrow stimulating factors other than
                          erythropoietin. 5. Systemic glucocorticoid
                          steroids at doses sufficient to affect the
                          immune response within the last 2 months. In
                          general this would mean an equivalent of more
                          than 20 mg of prednisone for more than 1
                          week. Replacement glucocorticoid therapy is
                          allowed.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Hepatic
                          dysfunction or congestive heart failure. 2.
                          Clinically significant autoimmune disease. 3.
                          Active, gross gastrointestinal bleeding or
                          uncontrolled peptic ulcer disease. 4.
                          Malignant tumors other than KS unless: 1) in
                          a complete remission for greater than or
                          equal to 1 year from the time a response was
                          first documented; 2) completely resected
                          basal cell carcinoma; or 3) in situ squamous
                          cell carcinoma of the cervix or anus. 5.
                          Other abnormality, except lymphopenia or
                          direct manifestations of KS, that would be
                          scored as Grade 3 toxicity. 6.
                          Hypersensitivity to IL-12 or other compounds
                          that are known to cross-react with IL-12. 7.
                          Medical condition that, in the opinion of the
                          principal investigator or study chairperson,
                          would preclude the inclusion of a patient
                          onto this research study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0259  Interleukin-12
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0185  Doxorubicin hydrochloride
                          (liposomal)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Induction Phase (6
                          3-week cycles): 300 ng/kg dose twiceweekly.
                          Maintenance Phase: 500 ng/kg dose twice
                          weekly. Drug 2: Induction Phase (6 3-week
                          cycles): 20 mg/m2 dose
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous. Drug 2:
                          Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: Approximately 3 years.
OTHER TREATMENT INFO.     END POINT: Toxicity and efficacy.
SUPPORTING AGENCY         Natl Cancer Institute.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 010322.

37
UNIQUE IDENTIFIER         NIH/01370
PROTOCOL ID NUMBERS       CC 00 C-0193
PROTOCOL TITLE            A Study of the Effects of Potent Anti-HIV
                          Therapy on Parameters Hypothesized to Be
                          Related to the Pathogenesis of Kaposi's
                          Sarcoma (KS) in HIV Infected Individuals.
TRIAL CATEGORY            AIDS-Related Malignancies
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To assess the initiation of potent
                          anti-HIV therapy on specific factors possibly
                          linked to the control or pathogenesis of
                          Kaposi's sarcoma (KS), namely serum viral
                          interleukin-6 (IL-6) and plasma VEGF levels
                          in patients with KS or at risk for KS by
                          virtue of being infected with Kaposi's
                          sarcoma-associated herpes virus (KSHV)/human
                          herpes virus-8 (HHV-8). To assess the effect
                          of the initiation of anti-HIV therapy on the
                          viral load of KSHV/HHV-8 in
                          KSHV/HHV-8-infected patients coinfected with
                          HIV.
GENERAL DESCRIPTION       RATIONALE: Certain blood proteins and a virus
                          called KSHV are thought to be factors
                          involved in causing KS in patients with HIV
                          infection or KS. This study uses certain
                          laboratory tests to examine the link between
                          anti-HIV therapy and the factors causing KS.
GENERAL DESCRIPTION       METHODOLOGY: Patients joining the study who
                          have not received anti-HIV therapy within the
                          last 4 weeks begin optimum anti-HIV therapy.
                          Patients joining the study who are already
                          taking anti-HIV therapy stop receiving
                          medications for 4 weeks, during which blood
                          tests are done to measure the effects of
                          stopping treatment on KSHV and other factors;
                          therapy is then restarted. Patients receive
                          up to 2 years of a combination of approved
                          anti-HIV medications while on the study.
                          During the study, blood and saliva samples
                          are tested for changes in immune function
                          directed at KSHV and blood proteins that may
                          be linked with KS. Patients with KS lesions
                          have lesions biopsied for possible
                          immune-related changes and are evaluated for
                          clinical response to treatment.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Clinical Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: About 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/24.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (010125)
PROTOCOL DETAILS          DISEASE STUDIED: Sarcoma, Kaposi.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: 00-C-0193
PROTOCOL DETAILS          STUDY DESIGN: Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-seropositivity. 2. Have a diagnosis
                          of KS and/or HHV-8/KSHV seropositivity. 3.
                          Have consent of parent or guardian if under
                          18 years of age.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Included: Have had no prior
                          HIV therapy; have a requirement for change in
                          HIV therapy and are naive to at least 2
                          anti-HIV drugs; or are on effective therapy
                          but willing to suspend therapy for at least 4
                          weeks.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Excluded: 1.
                          Investigator recommendation that
                          antiretroviral therapy is not in the best
                          interest of the patient. 2. Inability to
                          comply with protocol.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: None.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Specific
                          anti-KS therapy within 4 weeks of study
                          entry. 2. Corticosteroid therapy within 4
                          weeks prior to initiating study. 3. Cytokine
                          therapy within 4 weeks of study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Requirement for
                          specific anti-KS therapy. 2. Condition that
                          periodically requires immune-suppressive
                          therapy (e.g., asthma). 3. HIV-associated
                          opportunistic complications requiring
                          therapy.
SUPPORTING AGENCY         Natl Cancer Institute.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 010322.

38
UNIQUE IDENTIFIER         FDA/01369
PROTOCOL ID NUMBERS       FDA 302C
PROTOCOL TITLE            A Phase III Study Comparing the Antiviral
                          Efficacy and Safety of BMS-232632 with
                          Efavirenz; Each in Combination with Fixed
                          Dose Zidovudine-Lamivudine.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To compare the antiviral activity of
                          the 2 treatment arms through Week 48, based
                          on a comparison of the proportion of patients
                          responding to treatment with HIV RNA levels
                          less than 400 copies/ml for the
                          BMS-232632/efavirenz (EFV) placebo/zidovudine
                          (ZDV)-lamivudine (3TC) arm versus the
                          EFV/BMS-232632 placebo/ZDV-3TC arm.
                          Methodology: This is a multinational, 2-arm
                          study. Patients in 1 arm receive BMS-232632
                          plus EFV placebo capsules. Patients in the
                          other arm receive EFV plus BMS-232632
                          placebo. Both arms also receive a fixed dose
                          of ZDV-3TC.
GENERAL DESCRIPTION       METHODOLOGY: This is a multinational, 2-arm
                          study. Patients in 1 arm receive BMS-232632
                          plus EFV placebo capsules. Patients in the
                          other arm receive EFV plus BMS-232632
                          placebo. Both arms also receive a fixed dose
                          of ZDV-3TC.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010314)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 99
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AI424-034
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have plasma HIV RNA viral load of at least
                          2,000 copies/ml and a CD4 cell count of at
                          least 100 cells/mm3 (or at least 75 cells/mm3
                          if no prior history of AIDS-defining
                          diagnosis) obtained within 2 weeks prior to
                          randomization. 2. Be available for follow-up
                          for a period of at least 52 weeks. 3. Have
                          consent of parent or guardian if under 18
                          years of age.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3 Within
                          2 weeks prior to randomization.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN ULN (Upper Limit of
                          Normal). Within 2 weeks prior to beginning of
                          study drugs.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN Within 2 weeks prior to
                          beginning of study drugs.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN Within 2 weeks prior to
                          beginning of study drugs.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN Within 2 weeks prior
                          to beginning of study drugs.
PATIENT INCLUSION CRIT.   OTHER: Total serum lipase < 1.4 x ULN. Within
                          2 weeks prior to beginning of study drugs.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 16
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Proven or suspected acute hepatitis in the 30
                          days prior to study entry. Patients with
                          chronic hepatitis are eligible provided their
                          liver function enzymes are less than 3 times
                          the upper limit of normal. 2. Intractable
                          diarrhea (6 loose stools/day for at least 7
                          consecutive days) within 30 days prior to
                          study entry. 3. History of hemophilia. 4.
                          History or signs and symptoms of bilateral
                          peripheral neuropathy of Grade 2 or higher at
                          the time of screening.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          substance abuse sufficient to affect
                          compliance or increase the risk of developing
                          pancreatitis or chemical hepatitis.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy (30 days of nucleoside reverse
                          transcriptase inhibitor and/or 7 days of
                          nonnucleoside reverse transcriptase inhibitor
                          or protease inhibitor therapies) or any
                          antiretroviral therapy within 30 days prior
                          to screening. 2. Agents with significant
                          systemic myelosuppressive, neurotoxic,
                          pancreatotoxic, hepatotoxic, or cytotoxic
                          potential within 3 months prior to study
                          start or the expected need for such therapy
                          at the time of enrollment or therapy with
                          methadone or ribavirin/interferons or
                          treatment with neurotoxic drugs or drugs that
                          affect CYP3A4. 3. Other prior therapy, that
                          in the opinion of the investigator, would
                          make the subject unsuitable or unable to
                          comply with the dosing requirements.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Agents
                          with significant systemic myelosuppressive,
                          neurotoxic, pancreatotoxic, hepatotoxic, or
                          cytotoxic potential. 2. Methadone or
                          ribavirin/interferons or neurotoxic drugs or
                          drugs that affect CYP3A4.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Newly diagnosed
                          HIV-related opportunistic infection or any
                          medical condition requiring acute therapy at
                          the time of enrollment. 2. Inability to
                          tolerate oral medications. 3. Suspected
                          primary (acute) HIV infection. 4. Other
                          clinical conditions that, in the opinion of
                          the investigator, would make the patient
                          unsuitable for the study or unable to comply
                          with the dosing requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0314  BMS-232632
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0285  Lamivudine/Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0269  Efavirenz
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 200 mg bid. Drug 3:
                          200 mg tid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 400 mg. Drug 3: 600 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
SUPPORTING AGENCY         Bristol - Myers Squibb Pharmaceutical
                          Research Institute.
LAST REVISION DATE        20010314
ARIZONA                   Phoenix Body Positive 1144 East McDowell Road
                          Phoenix, AZ 85006 Barbara Casimir
                          [phone] Recruiting 010420.
ARIZONA                   Univ of British Columbia Department of
                          Pharmacology and Therapeutics / 2176 Health
                          ScienMall/Rm 305 Vancouver, BC Bobbi Zastre
                          [phone] Recruiting 010420.
CALIFORNIA                Saint Francis Mem Hosp / HIV Care Unit 4th
                          Floor / 900 Hyde St San Francisco, CA 94109
                          Karen Stonaker [phone] Recruiting
                          010420.
CALIFORNIA                Univ of Southern California SP21 Rand
                          Schrader Clinic / 1300 N Mission Rd Rm 349
                          Los Angeles, CA 90033 Luis Mendez
                          [phone] Recruiting 010420.
DISTRICT OF COLUMBIA      Dr Bruce Rashbaum Suite 401 / 2311 M St NW
                          Washington, DC 20037 Alex Seymour
                          [phone] Recruiting 010420.
DISTRICT OF COLUMBIA      Dupont Circle Physicians Group 1737 20th St
                          NW Washington, DC 200091104 Linda Green
                          [phone] Recruiting 010420.
FLORIDA                   Associates in Research 3677 Central Ave /
                          Suite D Fort Myers, FL 33901 Jaye Popoli
                          [phone] Recruiting 010420.
FLORIDA                   Steinhart Medical Associates 3659 South Miami
                          Ave / Suite 4006 Miami, FL 33133 Amy Liebmann
                          [phone] Recruiting 010420.
FLORIDA                   Saint Josephs Comprehensive Research
                          Institute 4200 N Armenia Ave / Suite 3 Tampa,
                          FL 33607 Allis Emnett [phone]
                          Recruiting 010420.
FLORIDA                   North Broward Hosp District / HIV Clinical
                          Research 1101 NW 1st St Fort Lauderdale, FL
                          33311 Elaine DiVeronica [phone]
                          Recruiting 010420.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Ericka Patrick [phone] Recruiting
                          010420.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Jaci Imberger [phone]
                          Recruiting 010420.
KANSAS                    Univ of Kansas School of Medicine 1010 North
                          Kansas St Wichita, KS 672143124 Janice
                          Cerrulo [phone] Recruiting 010420.
MICHIGAN                  Univ of Michigan Hospitals and Health Ctrs
                          3120 Taubman Ctr Ann Arbor, MI 481090378
                          Maggie Catoe [phone] Recruiting 010420.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          010420.
NORTH CAROLINA            Jemsek Clinic 16630 Northcross Dr / Suite 102
                          Huntersville, NC 28078 Paula Hutcherson
                          [phone] Recruiting 010420.
NORTH CAROLINA            Duke Univ Med Ctr / Infectious Disease Clinic
                          South Hosp Box 3306 / Trent Dr Durham, NC
                          27710 Meg McDaniel [phone] Recruiting
                          010420.
NEBRASKA                  Univ of Nebraska Medical Ctr 985400 Nebraska
                          Medical Ctr Omaha, NE 681985400 Michelle
                          Brester [phone] Recruiting 010420.
NEW JERSEY                Robert Wood Johnson Med School/UMDNJ 1 Robert
                          Wood Johnson Place New Brunswick, NJ
                          089030019 Tammy Hojeibane [phone]
                          Recruiting 010420.
NEW JERSEY                ID Care Inc 411 Courtyard Dr Somerville, NJ
                          08876 Debbie Winters [phone] Recruiting
                          010420.
NEW JERSEY                UMDNJ - New Jersey Med School 185 South
                          Orange Ave Newark, NJ 071032757 Carolyn
                          Rogers [phone] Recruiting 010420.
NEW MEXICO                Univ of NM 915 Camino de Salud NE
                          Albuquerque, NM 87131 Cynthia Nicholson
                          [phone] Recruiting 010420.
OHIO                      Ohio State Univ Hosp 456 West 10th Ave / Room
                          4725 Columbus, OH 432101282 Jane Russell
                          [phone] Recruiting 010420.
OTHER                     Ospedale S Raffaele Via Stamira D Ancona / 20
                          Milano, Adriano Lazzarin (39 )02 -2643 7934
                          Recruiting 010420.
OTHER                     Hosp Roosevelt Chief Infectious Diseases Unit
                          Calzada Roosevelt Zona 11 Guatemala, Carlos
                          R.
OTHER                     Hosp Ramon y Cajal Infectious Diseases
                          Service / Ctra Colmenar / Km 9.
OTHER                     Brooklyn Med Ctr 379 Koeberg Rd / Rugby Cape
                          Town, S Andrews Recruiting 010420.
OTHER                     Hosp Nuestra Senora de Covadonga C /
                          Celestino Villamil s/n Oviedo , J Antonio
                          Carton (34 )98 -510 8000 Recruiting 010420.
OTHER                     Toga Lab Unit 7A / Corner Dick Kemp and
                          Herman Streets / Meadowdale Johannesburg, Des
                          Martin (27 )11 -453 5066 Recruiting 010420.
OTHER                     Hosp Nacional Cayetano Heredia Av Honorio
                          Delgado s/n SMP Lima 31 Lima, Juan Echevarria
                          (511) 48-2 3910 Recruiting 010420.
OTHER                     King's College Hosp Caldercot Centre / 15-22
                          Caldercot Road Cambewell, Philippa
                          Easterbrook (44 )20 -7346 3479 Recruiting
                          010420.
OTHER                     Hopital Cochin - Port Royal 27 rue du
                          Faubourg Saint Jacques Paris, Dominique
                          Salmon-Ceron (33 )158- 41 2129 Recruiting
                          010420.
OTHER                     Hosp Nacional Arzobispo Loayza-PROCETS Av
                          Alfonso Ugarte 848 Lima 1 Lima, Aldo Vivar
                          (511) 43-1 3799 Recruiting 010420.
OTHER                     Hosp Guillermo Almenara-Medicina 1 Av Grau
                          800 La Victoria Lima 13 Lima, Raul Salazar
                          (511) 32-4 2952 Recruiting 010420.
OTHER                     Hopital Hotel Dieu de Lyon 1 Place de le
                          Hospital / Lyon Cedex 02 Lyon, Christian
                          Trepo (33 )4 7-2 41 3089 Recruiting 010420.
OTHER                     Hosp Edgardo Rebagliati Av Domingo Cueto s/n
                          Lima 11 Lima, Marco Montiel (511) 26-4 4901
                          Recruiting 010420.
OTHER                     Hosp Sotero de Rio Av Concha y Toro 3459
                          Puente Alto Santiago de Chile Santiago, Luis
                          Noriega (562) 29-5 5026 Recruiting 010420.
OTHER                     Ospedale S Orsola Devision Malattie Infettive
                          / Via Massarenti 11 Bologna, Francesco Chiodo
                          (39 )051- 3414 49 Recruiting 010420.
OTHER                     Royal Free Hosp Pond Street London, Margaret
                          Johnson (020)783-02589 Recruiting 010420.
OTHER                     Ospedale Luigi Sacco Cargnel Via G B Grassi
                          74 Milano, Antonietta Cargnel (39 )02 -3579
                          9379 Recruiting 010420.
OTHER                     Hosp Nacional dos de Mayo Parque Historia de
                          la Medicina Peruana Lima, Eduardo Ticona
                          (511) 32-8 2451 Recruiting 010420.
OTHER                     Servicio de Dermatologia-Hosp del Salvador Av
                          Salvador 360 Providencia Santiago de Chile
                          Santiago, Juan Ballesteros (526) 34-0 4575
                          Recruiting 010420.
OTHER                     Hosp Clinico de La Pontificia Universidad
                          Catolica de Chile Marcoleta 367 Santiago de
                          Chile Santiago, Carlos Perez (526) 63-2 4864
                          Recruiting 010420.
OTHER                     Services des Maladies Infectieuses 33 Blvd de
                          Picpus Paris Cedex 12, Willy Rozenbaum (33
                          )140- 19 3030 Recruiting 010420.
OTHER                     Tygerberg Hosp Infectious Diseases Clinic 8th
                          Floor East Site / Fransie Van ZyRoad Parow
                          Cape Town, Michele Zeir (021) 93-8 5230
                          Recruiting 010420.
OTHER                     Hosp General San Juan de Dios 1a Av 11-19 /
                          Zona 1 Guatemala, Eduardo Arathoon (502) 23-2
                          9589 Recruiting 010420.
OTHER                     Hosp Dr Domingo Luciani Final de la av Rio de
                          Janero / El Llanito / Petare Miranda, Anselmo
                          Rosales (257) 46-30 4883 Recruiting 010420.
OTHER                     Hosp U de Caracas / Ciudad UCV / piso 2
                          Servicio de Enfermededades Infecciosas
                          Adultos / LChaguaramos Caracas, Marisela
                          Silva (582) 66-2 6091 Recruiting 010420.
OTHER                     Hosp Vargas de Caracas Esquina Pirineos / San
                          Jose Caracas, Manuel Cortesia Recruiting
                          010420.
OTHER                     Consultorio Royal Ctr Seccion A / Primer Piso
                          No 108 / Zona 5 Panama, Nestor Sosa (507)
                          26-3 3464 Recruiting 010420.
OTHER                     Hosp Germans Trias I Pujol Consultas Vih /
                          Ctra Del Canyet S/N / Badalona Barcelona,
                          Bonaventura Clotet (34 )93 -497 8887
                          Recruiting 010420.
OTHER                     CHU De Bicetre 78 Rue Du General Leclerc
                          Paris, Jean-Fancois Delfraissy (33 )145- 21
                          2891 Recruiting 010420.
OTHER                     Univ Zu Koeln Medizinische Klinik 1 / Haus
                          116 - Joseph-Str 9 Koeln, Gerd Fatkenheuer
                          (022)1 2-78 4886 Recruiting 010420.
OTHER                     Universitatsspital Zurich Ramistrasse 100
                          Zurich, Markus Flepp (41 )125-5 3222
                          Recruiting 010420.
OTHER                     Hosp Carlos III Servicio De Infecciosos / C
                          Sinesio Delgado 10-12 Madrid, Juan
                          Gonzalez-Lahoz (34 )91 -453 2500 Recruiting
                          010420.
OTHER                     Pulmologisches Zentrum Der Stadt Wien
                          Immunambulanz / Sanatoriumsstr 2 Wien,
                          Norbert Vetter (41 )910-60 42001 Recruiting
                          010420.
OTHER                     Hospital Gustave Dron 135 Rue du President
                          Coty Tourcoing, Yves Mouton (33 )3 2-0 69
                          4600 Recruiting 010420.
OTHER                     Chiangmai Univ Dept of Med / 5th Floor /
                          Boonsom-Martin Chiang Mai, Khuanchai
                          Supparatpinyo (665)3 8-95015 Recruiting
                          010420.
OTHER                     Hosp Virgen Del Rocio Consultas HIV / Avda
                          Manuel Siurot S/N Sevilla, Pompeyo Viciana
                          (34 )95 -424 7628 Recruiting 010420.
OTHER                     Kaplan Med Ctr Ruth Ben Ari Institute of
                          Clinical Immunology and / AIDS CenterRehovot,
                          Zvi Bentwich (972) 8 -9441 444 Recruiting
                          010420.
OTHER                     Vajira Hosp Dept of Preventative and Social
                          Med / 1st Floor / Muslim Bldg Bangkok,
                          Wanchai Buppanharun (662) 24-3 0151 79
                          Recruiting 010420.
OTHER                     Univ of Malaya Med Ctr Madam Margaret Tan
                          Clinical Investigation Ctr Kuala Lumpur,
                          Adeeba Kamarulzaman (603) 79-50 2351
                          Recruiting 010420.
OTHER                     Hosp Kuala Lumpur Ward P1 Kuala Lumpur,
                          Christopher Lee (603) 26-90 6521 Recruiting
                          010420.
OTHER                     Ospedale Amedeo de Savoia Divisione Malattie
                          Infettive / Corso Svizzera 164 Torino, Maria
                          Luisa Soranzo (39 )011- 4393 856 Recruiting
                          010420.
OTHER                     AKH Wien Abt Fur Immundermatologie /
                          Wahrinqerqurtel 18-20 Wien, Armin Rieger (43
                          )140-400 7701 Recruiting 010420.
OTHER                     Siriraj Hosp / Mahidol Univ 4th Floor/Pa-Ob
                          Bldg / Pranrok Road Bangkok, Thanoksak
                          Anekthanonon (662) 41-9 7387 8 Recruiting
                          010420.
OTHER                     Rheinische Friedrich Wilhelms Universitaet
                          Medizinische Siegmund Freud Strasse 25 Bonn,
                          Jurgen Rockstroh (022)8 2-87 5260 Recruiting
                          010420.
OTHER                     UZ Gasthuisberg Afdoling IG Algernene /
                          Herestraat 49 Leuven , Eric Van Wijngaerden
                          (016) 34- 42 75 Recruiting 010420.
OTHER                     Ospedale Amedeo di Savoia Clinica
                          Universitaria / Corso Svizzera 164 Torino,
                          Giovanni Di Perri (39 )011- 43 93828
                          Recruiting 010420.
OTHER                     Saint Laszlo Hosp 5th Dept of Infectious
                          Diseases / Gyali ut 5-7 Budapest, Denes
                          Banhegyi (003)6 1- 455 8152 Recruiting
                          010420.
OTHER                     Cat All Immun Clin Univ La Sapienza Roma /
                          Vialle Dell Universita 37 Roma, R Aiuti (39
                          )064- 9972 007 Recruiting 010420.
OTHER                     Immunoligia Universita Cagliari Dipartimento
                          Scienze Mediche / Policlinico U Cagliari,
                          Pier Emilio Manconi (39 )070- 520 755
                          Recruiting 010420.
OTHER                     Hosp De Sao Joao Servico De Doencas
                          Infecciosas Porto, Mota Miranda (351) 22- 550
                          1727 Recruiting 010420.
OTHER                     Hosp De Santa Maria Servicio De Doencas
                          Infecciosas / Av Prof Egaz Moniz Lisboa,
                          Francisco Antunes (351) 21- 793 8043
                          Recruiting 010420.
OTHER                     CHU Saint Pierre Rue Haute 322 Brussels,
                          Nathan Clumeck (02 )535- 41 31 Recruiting
                          010420.
OTHER                     Federal AIDS Ctr 15 Sokolinoy Gory Vosmaya
                          Ulitsa Moscow, V Pokrovsky (709)5 3-65 3009
                          Recruiting 010420.
OTHER                     Ospedale degli Infermi Divisione Malattie
                          Infettive / Via Settembini 2 Rimini, R
                          Ciammarughi (37 )054- 1705 315 Recruiting
                          010420.
OTHER                     Fundacion Arriaran Santa Elvira 629 Santiago
                          de Chile Santiago, Mercelo Wolff (562) 55-1
                          6738 Recruiting 010420.
OTHER                     Infectious Hosp 30 3 Mirgorodskaya St St
                          Petersburg, A Yakovlev (781)2 2-77 2848
                          Recruiting 010420.
OTHER                     Hosp Clinic C/Villarroel / 170 Barcelona,
                          Jose Maria Gatell (34 )93 -227 5574
                          Recruiting 010420.
OTHER                     Ust Izhora Fed Infectious Hosp Prospect
                          Devyatogo Yanvarya / Bldg 3 St Petersburg, E
                          Voronin (781)2 4-64 9329 Recruiting 010420.
OTHER                     Hosp de Basurto / Enfermedades Infecciosas
                          Pabellon Revilla 3a planta / Avenida de
                          Montevideo 16-18 Bilboa, Juan Miguel Santa
                          Maria (34 )94 -441 8800 Recruiting 010420.
OTHER                     Hosp Reina Sofia Enfermedades Infecciosas /
                          Avda Menendez Pidal / s/n Cordoba, Antonio
                          Rivero (34 )95 -721 7645 Recruiting 010420.
OTHER                     Chris Hani Baragwanath Hosp Perinatal HIV
                          Research Unit / Maternity Sector / Old Potch
                          RoadSoweto Johannesburg, A Karstaedt
                          Recruiting 010420.
OTHER                     Saint James Hosp Genito Urinary Clin / James
                          St Dublin, Fiona Mulcahy (353) 14-16 2590
                          Recruiting 010420.
OTHER                     Rajavithi Hosp Dept of Med / 2nd Floor /
                          Addict Bldg Bangkok, Naruemon Pongsripian
                          (662) 24-5 3120 Recruiting 010420.
OTHER                     Ramathibodi Hosp Dept of Med / 9th Floor /
                          Rama VI Rd Bangkok, Asda Vibhagool (662) 20-1
                          2107 Recruiting 010420.
OTHER                     SEMECO Calle 17 bis / Avenidas 9 y 11 / Casa
                          962 / Barrio Aranjuez San Jose, Gisela
                          Herrera (506) 25-8 5185 Recruiting 010420.
OTHER                     Univ of Alberta/Division of Inf Dis/Dept of
                          Med 24E13 Walter MacKenzie Edmonton , AB
                          Laura Mishner [phone] Recruiting
                          010420.
OTHER                     McMaster Univ Med Ctr 1200 Main Street West
                          Hamilton , ON Lynn Kelleher [phone]
                          Recruiting 010420.
OTHER                     Gary Rubin 406-235 Danforth Ave Toronto, ON
                          [phone] Recruiting 010420.
OTHER                     Clinical Research Puerto Rico Inc 355 De
                          Diego Ave San Juan, PR 009091711 Ana Campos
                          [phone] Recruiting 010420.
OTHER                     San Juan VAMC 10 Casia St San Juan, PR
                          009265800 Zydnia Pomales [phone]
                          Recruiting 010420.
PENNSYLVANIA              Philadelphia FIGHT / Jay Kostman 1233 Locust
                          St Philadelphia, PA 19107 Kelly Novitski
                          [phone] Recruiting 010420.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Ann Arroyo
                          [phone] Recruiting 010420.
TENNESSEE                 Methodist Healthcare 1265 Union Avenue
                          Memphis, TN 38104 Debra Terry [phone]
                          Recruiting 010420.
TEXAS                     Tarrant County Infectious Diseases Associates
                          Suite 110 / 1325 Pennsylvania Ave Fort Worth,
                          TX 76104 Tara Weaver [phone] Recruiting
                          010420.
TEXAS                     Montrose Clinic 215 Westheimer Rd Houston, TX
                          77006 Mark Mall [phone] Recruiting
                          010420.
TEXAS                     Oaklawn Physicians Group 3514 Cedar Springs
                          Rd / Suite 200 Dallas, TX 75219 Gayle Trent
                          [phone] Recruiting 010420.

39
UNIQUE IDENTIFIER         FDA/01367
PROTOCOL ID NUMBERS       FDA B012
PROTOCOL TITLE            A Randomized Controlled Study Testing the
                          Efficacy of Immunotherapies to Control Plasma
                          HIV RNA Concentrations Upon Interruption of
                          Highly Active Antiretroviral Therapy.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Therapeutic AIDS Vaccine
GENERAL DESCRIPTION       PURPOSE: To determine whether HIV-specific
                          canarypox vector immunizations and/or daily
                          low-dose interleukin-2 (IL-2) result in
                          efficient immune control of viral replication
                          subsequent to an interruption of HAART.
                          Methodology: Step I: In addition to
                          continuing HAART, patients are randomized
                          into 1 of the following 4 arms: A:
                          Immunization placebo; B: Immunization with
                          the canarypox HIV-vaccine (vCP1452); C: Daily
                          low-dose IL-2 + immunization placebo; or D:
                          Daily low-dose IL-2 + canarypox HIV-vaccine
                          (vCP1452). Patients on Arms A, B, C, and D
                          receive vaccine (or vaccine placebo)
                          injections at Weeks 0, 4, 8, and 12. Patients
                          on Arms C and D receive IL-2 by
                          self-injection. HAART is not provided as part
                          of this study. Step II: Patients on all arms
                          (A, B, C, and D) who meet inclusion criteria
                          advance to Step II and interrupt HAART for a
                          minimum of 12 weeks. The efficacy of these
                          immunological therapies will be determined by
                          monitoring the dynamics of viral rebound upon
                          cessation of antiviral therapy. After 12
                          weeks of Step II, patients whose viral load
                          remains below 30,000 copies/ml remain on Step
                          II, off HAART, and continue weekly viral load
                          monitoring. Patients will not terminate Step
                          II or resume HAART unless and until their
                          viral load increases to more than 30,000
                          copies/ml on 3 successive determinations, or
                          their CD4 count decreases to less than 200
                          cells/mm3 or less than 50 percent of the
                          baseline CD4+ T cell concentration on 2
                          successive occasions.
GENERAL DESCRIPTION       METHODOLOGY: Step I: In addition to
                          continuing HAART, patients are randomized
                          into 1 of the following 4 arms: A:
                          Immunization placebo; B: Immunization with
                          the canarypox HIV-vaccine (vCP1452); C: Daily
                          low-dose IL-2 + immunization placebo; or D:
                          Daily low-dose IL-2 + canarypox HIV-vaccine
                          (vCP1452). Patients on Arms A, B, C, and D
                          receive vaccine (or vaccine placebo)
                          injections at Weeks 0, 4, 8, and 12. Patients
                          on Arms C and D receive IL-2 by
                          self-injection. HAART is not provided as part
                          of this study. Step II: Patients on all arms
                          (A, B, C, and D) who meet inclusion criteria
                          advance to Step II and interrupt HAART for a
                          minimum of 12 weeks. The efficacy of these
                          immunological therapies will be determined by
                          monitoring the dynamics of viral rebound upon
                          cessation of antiviral therapy. After 12
                          weeks of Step II, patients whose viral load
                          remains below 30,000 copies/ml remain on Step
                          II, off HAART, and continue weekly viral load
                          monitoring. Patients will not terminate Step
                          II or resume HAART unless and until their
                          viral load increases to more than 30,000
                          copies/ml on 3 successive determinations, or
                          their CD4 count decreases to less than 200
                          cells/mm3 or less than 50 percent of the
                          baseline CD4+ T cell concentration on 2
                          successive occasions.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010606)
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy, Immunotherapy, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 92 patients. 4 arms of 23
                          patients each.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 25 weeks and
                          every 4 weeks after week 25 for follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/92.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: 0900-397
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method; Random
                          Allocation; Factorial Design Study;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV seropositivity as documented by
                          ELISA and Western blot analysis. 2. Have CD4+
                          T cell levels of 200 cells/microL or higher
                          within the 12 months prior to enrollment, and
                          CD4+ T cells of 400 cells/microL or more on 2
                          successive occasions at least 14 days apart
                          within 30 days of study entry. 3. Have
                          documentation that plasma HIV RNA
                          concentrations have never been higher than 2
                          million molecules/ml, and of suppression on
                          HAART to less than 50 molecules/ml on 2
                          successive occasions at least 14 days apart
                          within 30 days of entry. 4. Have no history
                          of virologic failure (i.e., greater than
                          10,000 HIV RNA molecules/ml) while receiving
                          current HAART regimen.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.1 g/dl for males and >= 8.9
                          g/dl for females, within 30 days of entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/microL On 2
                          successive occasions at least 14 days apart
                          within 30 days of entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN ULN (Upper Limit of
                          Normal). Within 30 days of entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= ULN. Within 30 days of entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN Within 30 days of
                          entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry Negative pregnancy test.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable HAART
                          (defined as 2 or more antiretroviral drugs in
                          combination) for at least 6 months
                          consecutively.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. Topical
                          corticosteroids at a site separate from IL-2
                          and vaccine injection sites. 2. Maintenance
                          therapy for opportunistic infections that
                          develop on study treatment according to
                          standard medical care, except for foscarnet
                          during IL-2 administration, and rifabutin and
                          rifampin at any time. 3. Maintenance therapy
                          for recurrent genital herpes with 1000 mg/day
                          or less of acyclovir. 4. Erythropoietin and
                          filgrastim (G-CSF) when clinically indicated.
                          5. Antibiotics for bacterial infections as
                          clinically indicated. 6. Medications for
                          symptomatic treatment such as antipyretics
                          and analgesics. Ibuprofen and acetaminophen
                          are the preferred agents.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 19
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Documentation of virologic failure (i.e.,
                          higher than 10,000 HIV RNA molecules/ml)
                          while receiving current HAART regimen. 2.
                          Malignancy requiring chemotherapy. 3.
                          Untreated thyroid disease, with the exception
                          of treated and stable hyperthyroidism or
                          hypothyroidism for at least 4 weeks prior to
                          entry. 4. Uncontrolled allergic disorders or
                          autoimmune diseases, including asthma,
                          inflammatory bowel disease, and psoriasis. 5.
                          Egg allergy.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active substance
                          abuse that will compromise the patient's
                          ability to adhere to the study requirements.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. History of
                          immunomodulating agents including: other
                          interleukins; antibodies reactive with
                          lymphocytes, monocytes, or antigen-presenting
                          cells; and polyribonucleotides. 2. IL-2
                          therapy within 4 weeks of entry. 3. Other
                          known immunomodulatory therapies within 4
                          weeks of entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Prohibited:
                          Interferons; interleukins (other than the
                          study IL-2); sargramostim (GM-CSF);
                          dinitrochlorobenzene (DNCB); thymosin alpha 1
                          (thymosin alpha); thymopentin; inosiplex;
                          polyribonucleoside; ditiocarb sodium;
                          investigational antiretroviral agents;
                          thalidomide; St. John's wort; systemic or
                          local cytotoxic chemotherapy for malignancy;
                          and systemic corticosteroids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Current
                          AIDS-defining illness. 2. Uncontrolled active
                          cardiac disease. 3. Active coinfection with
                          hepatitis B virus or hepatitis C virus, as
                          defined by detectable viremia. 4.
                          Professionals working in close contact with
                          canaries (e.g., breeding farms and bird
                          shops), who are likely to have antibodies to
                          canarypox prior to vaccination.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 1 ml (greater than
                          or equal to 10^6.5 TCID50) at Weeks 8, and
                          12. Drug 2: 1.2 MU/m2 daily
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 2: 1.2 MU/m2
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          SC
OTHER TREATMENT INFO.     TREATMENT DURATION: A maximum of 25 weeks.
OTHER TREATMENT INFO.     END POINT: Mean log10 viral load for each
                          experimental group from the average of 5
                          values obtained during Weeks 8-12 following
                          the interruption of HAART.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reason: 1. Inability to
                          maintain viral load criteria, for Steps I and
                          II. 2. CD4+ cell level falls below 200
                          cells/microL, or below 50 percent of the
                          baseline determinations on 2 successive
                          occasions performed at least 1 week apart,
                          for Step II. 3. Noncompliance: The patient
                          takes no study medications or discontinues
                          these medicines following randomization to
                          Step I. 4. Nonadherence with clinical visits.
                          5. Treatment-related toxicity that requires
                          permanent study treatment discontinuation. 6.
                          Requirement for any prohibited medications.
                          7. Voluntary withdrawal. 8. Pregnancy and
                          breast-feeding. The patient will be followed
                          for safety for at least 1 month. Fetal
                          outcome, if available, will be recorded in
                          the clinic chart.
OTHER TREATMENT INFO.     MODIFICATION: This protocol allows for 1 dose
                          level reduction of IL-2 of 25 percent to 0.9
                          MU/m2.
SUPPORTING AGENCY         New York Hosp - Cornell Med Ctr.
LAST REVISION DATE        20010606
NEW YORK                  New York Hosp - Cornell Med Ctr 525 East 68th
                          St New York, NY 10021 Ann Dunne [phone]
                          Recruiting 010110.

40
UNIQUE IDENTIFIER         FDA/01366
PROTOCOL ID NUMBERS       FDA B011
PROTOCOL TITLE            A Phase I Study of Aventis Pasteur Live
                          Recombinant ALVAC-HIV (vCP205, HIV-1
                          env/gag/pol) in Seronegative Adults
                          Administered (1) Subcutaneously via ex vivo
                          Transfected, Autologous Dendritic Cells, (2)
                          Intradermally, or (3) Intramuscularly.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Preventative HIV Vaccine
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and
                          immunogenicity of new delivery routes for the
                          existing canarypox HIV vaccine candidate,
                          ALVAC HIV-1 (vCP205). Methodology: Healthy
                          adult volunteers are assigned randomly to
                          either a vaccine or placebo group. Injections
                          are received either intramuscularly,
                          intradermally, or by delivery under the skin
                          of the volunteer's own white blood cells
                          which have had dendritic cell reinfusion.
                          Volunteers are vaccinated at 0, 1, 3, and 6
                          month time points. Volunteers are closely
                          monitored for 1 hour after vaccination and
                          keep a diary of symptoms for 1 week
                          post-immunization. Volunteers undergo
                          leukopheresis at the start of the study and
                          after the last vaccination at Walter Reed
                          Army Medical Center. Volunteers receive
                          compensation benefits.
GENERAL DESCRIPTION       METHODOLOGY: Healthy adult volunteers are
                          assigned randomly to either a vaccine or
                          placebo group. Injections are received either
                          intramuscularly, intradermally, or by
                          delivery under the skin of the volunteer's
                          own white blood cells which have had
                          dendritic cell reinfusion. Volunteers are
                          vaccinated at 0, 1, 3, and 6 month time
                          points. Volunteers are closely monitored for
                          1 hour after vaccination and keep a diary of
                          symptoms for 1 week post-immunization.
                          Volunteers undergo leukopheresis at the start
                          of the study and after the last vaccination
                          at Walter Reed Army Medical Center.
                          Volunteers receive compensation benefits.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010618)
PROTOCOL DETAILS          STUDY INTENT: Vaccine prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 36 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 14 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/36.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: RV 138
PROTOCOL DETAILS          STUDY DESIGN: Random Allocation; Randomized
                          Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must:
                          Be in good health. Be legal US residents.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 55 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Excluded:
                          HIV-positive individuals. Individuals at
                          highest risk for HIV infection.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Use of
                          certain prescription medications.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: Allergy to eggs or
                          neomycin.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0230  ALVAC-HIV MN120TMG (vCP205)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Vaccine Group: 0, 1,
                          3, and 6 months
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneously,
                          intradermally, or intramuscularly
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 months.
SUPPORTING AGENCY         Walter Reed Army Institute of Research
                          (WRAIR).
LAST REVISION DATE        20010618
MARYLAND                  Walter Reed Army Institute of Research
                          (WRAIR) Vaccine Clinical Research Center /
                          1600 E Gude Dr Rockville, MD 20850 Catherine
                          Chaddic [phone] Recruiting 010202.

41
UNIQUE IDENTIFIER         FDA/01365
PROTOCOL ID NUMBERS       FDA 308B
PROTOCOL TITLE            A Phase IV Multicenter Study of the Efficacy
                          and Safety of 48-Week Induction Treatment
                          with TRIZIVIR (Abacavir 300 mg/Lamivudine 150
                          mg/Zidovudine 300 mg Combination Tablet BID)
                          with Efavirenz (600 mg QD) Followed by
                          48-Week Randomized, Open-Label, Maintenance
                          Treatment with TRIZIVIR with or without
                          Efavirenz in HIV-1 Infected Antiretroviral
                          Therap
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To assess durability of suppression
                          of plasma HIV-1 RNA with Trizivir (TZV) with
                          or without efavirenz (EFV) during the 48-week
                          Maintenance Phase following the 48-week
                          Induction Phase.
GENERAL DESCRIPTION       RATIONALE:
GENERAL DESCRIPTION       METHODOLOGY: Patients receive TZV plus EFV in
                          the 48-week Induction Phase. Eligible
                          patients, defined as those with plasma HIV-1
                          RNA under 50 copies/ml, participate in the
                          48-week Maintenance Phase. Patients are
                          randomized equally to receive either TZV plus
                          EFV or TZV alone. An immunology substudy will
                          be conducted, including approximately the
                          first 100 patients enrolled who agree to
                          participate.
PROTOCOL PHASE            Phase IV
OPEN/CLOSED INDICATOR     Open (010628)
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy, Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 400 patients.
                          Approximately 400 patients are enrolled into
                          the Induction Phase to ensure that
                          approximately 280 patients (140 per arm) will
                          be eligible
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Patients
                          participate in 2 weeks of screening and 48
                          weeks of Induction Therapy. If eligible,
                          patients participate in 48 weeks of
                          Maintenance Therapy. Patients are contacted
                          for follow-up 4 weeks after the last dose of
                          the study drug. Maximum dur
PROTOCOL DETAILS          ACTUAL ACCRUAL: 155/400 010628.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 42
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: ESS40013
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection documented by
                          screening plasma viremia of 5,000 copies/ml
                          or higher. 2. Adequate and reliable forms of
                          contraception, including complete abstinence
                          from intercourse starting at least 2 weeks
                          prior to the administration of study drug,
                          double barrier method, intrauterine device
                          with published data showing the expected
                          failure rate is less than 1 percent per year,
                          sterilization of female patient or male
                          partner of female patient, and any other
                          methods with published data showing that the
                          lowest expected failure rate for the method
                          is less than 1 percent per year. Note:
                          Hormonal contraception is not considered
                          adequate. 3. Consent of parent or guardian if
                          under 18.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10.0 g/dl (6.3 mmol/L) for men
                          and >= 9.0 g/dl (5.7 mmol/L) for women,
                          within 14 days prior to the first dose of
                          study medication.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3 Within 14 days
                          prior to the first dose of study medication.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: No requirement.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 14 days prior to
                          the first dose of study medication.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 14 days prior to
                          the first dose of study medication.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 40 ml/min Within 14
                          days prior to the first dose of study
                          medication.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test Abstinence
                          or effective (approved) method of birth
                          control.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: Inhaled
                          corticosteroids in asthmatic patients.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. Inhaled
                          corticosteroids in asthmatic patients. 2.
                          Chemoprophylaxis for HIV-associated
                          conditions. 3. Hematologic supportive therapy
                          with G-CSF or erythropoietin. 4. Non-HIV
                          vaccines, preferably given during or
                          immediately after a scheduled visit.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Clinically relevant hepatitis within 6 months
                          prior to screening. 2. Allergy to any of the
                          study drugs or any excipients therein.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Substance abuse
                          disorder which, in the opinion of the
                          investigator, may interfere with the
                          patient's ability to comply with the dosing
                          schedule and protocol evaluations and
                          assessments.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 4 weeks prior to entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Nonnucleoside
                          reverse transcriptase inhibitors. 2. Therapy,
                          with any licensed or investigational protease
                          inhibitor, nucleoside reverse transcriptase
                          inhibitor, or nucleotide reverse
                          transcriptase inhibitor, of 2 or more weeks
                          duration. 3. Cytotoxic chemotherapeutic
                          agents within 4 weeks prior to entry. 4.
                          Immunomodulating agents, such as systemic
                          corticosteroids, interleukins, vaccines, or
                          interferons, within 4 weeks prior to study
                          entry. 5. HIV immunotherapeutic vaccine
                          within 3 months prior to entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Nonnucleoside reverse transcriptase
                          inhibitors. 2. Any licensed or
                          investigational protease inhibitor,
                          nucleoside reverse transcriptase inhibitor,
                          or nucleotide reverse transcriptase
                          inhibitor. 3. Cytotoxic chemotherapeutic
                          agents. 4. Immunomodulating agents, such as
                          systemic corticosteroids, interleukins,
                          vaccines, or interferons. 5. HIV
                          immunotherapeutic vaccines. 6. Foscarnet
                          therapy or therapy with other agents with
                          documented activity against HIV-1 in vitro.
                          7. Astemizole, cisapride, midazolam,
                          triazolam, or ergot derivatives. 8. Other
                          experimental agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Active
                          AIDS-defining opportunistic infection or
                          disease according to the 1993 CDC AIDS
                          surveillance definition (Clinical Category C)
                          which, in the opinion of the investigator,
                          would preclude the patient from participating
                          in the study. 2. Inability, in the opinion of
                          the investigator, to complete the 96-week
                          dosing period and protocol evaluations and
                          assessments or to adhere to the study drug
                          regimen. 3. Mental or physical disorder
                          which, in the opinion of the investigator,
                          may interfere with the patient's ability to
                          comply with the dosing schedule and protocol
                          evaluations and assessments. 4. Serious
                          medical condition, such as diabetes,
                          congestive heart failure, cardiomyopathy, or
                          other cardiac dysfunction, which, in the
                          opinion of the investigator, would compromise
                          the safety of the patient. 5. Malabsorption
                          syndrome or other gastrointestinal
                          dysfunction, which may interfere with drug
                          absorption or render the patient unable to
                          take oral medication. 6. Clinically relevant
                          hepatitis. 7. Allergy to any of the study
                          drugs or any excipients therein.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0325
                          Lamivudine/Zidovudine/Abacavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: One combination
                          tablet (lamivudine 150 mg/zidovudine
                          30mg/abacavir 300 mg) bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Lamivudine 300
                          mg/zidovudine 600 mg/abacavir 600 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Patients receive
                          treatment for 48 weeks in the Induction Phase
                          and, if eligible, receive treatment for 48
                          weeks in the Maintenance Phase. Maximum
                          treatment duration is 96 weeks.
SUPPORTING AGENCY         GlaxoSmithKline.
LAST REVISION DATE        20010628
ARKANSAS                  Health for Life Clinic 123 North Van Buren
                          Little Rock, AR 72205 Ben Montgomery
                          [phone] Recruiting 010201.
ARIZONA                   Phoenix Body Positive 1144 East McDowell Road
                          Phoenix, AZ 85006 Linda Sirois [phone]
                          Recruiting 010201.
CALIFORNIA                Orange County Ctr for Special Immunology
                          11190 Warner Ave / Suite 411 Fountain Valley,
                          CA 92708 Sandy Cassarella [phone]
                          Recruiting 010201.
CALIFORNIA                Pacific Horizons Med Group 2351 Clay St San
                          Francisco, CA 94115 Jennifer Armfield
                          [phone] Recruiting 010201.
COLORADO                  Beacon Clinic / Boulder Community Hosp 1155
                          Alpine St Boulder, CO 80304 Anil Modak
                          [phone] Recruiting 010201.
DISTRICT OF COLUMBIA      Georgetown Univ Med Ctr 3800 Reservoir Rd NW
                          / 210 Kober-Cogan Building Washington, DC
                          20007 Scott Watson [phone] Recruiting
                          010201.
DISTRICT OF COLUMBIA      Dupont Circle Physicians Group 1737 20th St
                          NW Washington, DC 200091104 Linda Green
                          [phone] Recruiting 010201.
FLORIDA                   Univ of Miami / Jackson Memorial Hosp 1500
                          Northwest 12th Ave / 8th Floor Miami, FL
                          33136 Christopher Kazubski [phone]
                          Recruiting 010201.
FLORIDA                   SBMA Research 333 41st St Miami Beach, FL
                          33140 Doreen Garabedian [phone]
                          Recruiting 010201.
FLORIDA                   Infectious Disease Consultants 685 Palm
                          Springs Dr Altamonte Springs, FL 32701 Wendy
                          Simmons [phone] Recruiting 010201.
FLORIDA                   North Broward Hosp District / HIV Clinical
                          Research 1101 NW 1st St Fort Lauderdale, FL
                          33311 Howard Yontef [phone] Recruiting
                          010201.
GEORGIA                   Infectious Disease Specialists of Atlanta
                          2665 N Decatur Rd / Suite 330 Decatur, GA
                          30033 Katie McClure [phone] Recruiting
                          010201.
ILLINOIS                  Northstar Med Clinic 2835 North Sheffield Ave
                          Chicago, IL 60657 Tamara Hill [phone]
                          Recruiting 010201.
ILLINOIS                  Cook County Gen Hosp / Division of Infect
                          Diseases 2020 West Harrison Chicago, IL 60612
                          Jo Ann Despotes [phone] Recruiting
                          010201.
KENTUCKY                  University of Louisville / ID Division 511 S
                          Floyd St Louisville, KY 40202 Jayne Carwile
                          [phone] Recruiting 010201.
LOUISIANA                 HIV Outpatient Clinics / LA State Univ Med
                          Ctr 136 South Roman St New Orleans, LA 70112
                          Marsha Bennett [phone] Recruiting
                          010201.
MASSACHUSETTS             Boston Med Ctr 1 Boston Med Ctr Place /
                          Dowling Bldg Boston, MA 02118 Sue Bazner
                          [phone] Recruiting 010201.
MICHIGAN                  Dr Paul Benson 2327 Coolidge Berkley, MI
                          48072 Dorothy Dempster [phone]
                          Recruiting 010201.
MINNESOTA                 Regions Hosp / HIV/AIDS Program 640 Jackson
                          St / North Bldg St Paul, MN 55101 Jessica
                          Kopaczewski [phone] Recruiting 010201.
MINNESOTA                 Hennepin County Med Ctr 4th Floor N ID /
                          Clinic #834 / 701 Park Ave Minneapolis, MN
                          55415 Marcia Meredith [phone]
                          Recruiting 010628.
MISSISSIPPI               CRC of Mississippi 501 Marshall St Jackson,
                          MS 39202 Kevin Kantor [phone]
                          Recruiting 010201.
NORTH CAROLINA            ID Consultants 814 East Boulevard Charlotte,
                          NC 28203 Leslie Climer [phone]
                          Recruiting 010201.
NORTH CAROLINA            East Carolina Univ School of Medicine Section
                          of Infectious Diseases 3E-117 / Brody
                          Building Greenville, NC 27858 Grace Wilkins
                          [phone] Recruiting 010201.
NEW JERSEY                Hackensack University Medical Center 20
                          Prospect St Hackensack, NJ 07601 Terry
                          McKiernan [phone] Recruiting 010201.
NEW JERSEY                NJCRI 393 Central Ave / Suite 301 Newark, NJ
                          07103 Candace Tobin [phone] Recruiting
                          010201.
NEVADA                    Wellness Ctr / Las Vegas 2300 South Rancho
                          Blvd Las Vegas, NV 89102 Dennis Fuller
                          [phone] Recruiting 010201.
NEW YORK                  Aaron Diamond AIDS Rsch Ctr / Rockefeller
                          Univ 1230 York Ave New York, NY 10021 Arlene
                          Hurley [phone] Recruiting 010201.
NEW YORK                  SUNY / Health Sciences Ctr at Brooklyn 450
                          Clarkson Ave Brooklyn, NY 11203 Susan Holman
                          [phone] Recruiting 010201.
OHIO                      Summa Health System 75 Arch St Akron, OH
                          44304 Lisa Flood [phone] Recruiting
                          010201.
OKLAHOMA                  Univ of Oklahoma Infectious Disease Institute
                          835 Stanton L Young Blvd Oklahoma, OK 73117
                          Brenda Hood [phone] Recruiting 010201.
OKLAHOMA                  Associates in Med and Mental Health 2325
                          South Harvard / Suite 600 Tulsa, OK 74114
                          Marian Austin [phone] Recruiting
                          010201.
TENNESSEE                 Univ of Tennessee Med Ctr at Knoxville 1924
                          Alcoa Hwy / Clinical Trials Research Prog
                          Knoxville, TN 37920 Lacey Peltier
                          [phone] Recruiting 010201.
TEXAS                     Tarrant County Infectious Diseases Associates
                          Suite 110 / 1325 Pennsylvania Ave Fort Worth,
                          TX 76104 Tara Weaver [phone] Recruiting
                          010201.
TEXAS                     Metroplex Infectious Disease 1350 South Main
                          St Fort Worth, TX 76104 Michelle Bachman
                          [phone] Recruiting 010201.
TEXAS                     Diversified Med Practices PA 4126 Southwest
                          Freeway Houston, TX 77027 Barbara Knight
                          [phone] Recruiting 010201.
TEXAS                     Therapeutic Concepts 1200 Binz / Suite 120
                          Houston, TX 77004 Marketer Washington
                          [phone] Recruiting 010201.
TEXAS                     Infectious Diseases Associates of Houston
                          6560 Fannin / Suite 1540 Houston, TX 77030
                          Joni Blais [phone] Recruiting 010201.
TEXAS                     AIDS Outreach Center 801 West Cannon Fort
                          Worth, TX 76104 Mickey Howell [phone]
                          Recruiting 010201.
TEXAS                     Texas Tech Health Sciences Ctr 4800 Alberta
                          Ave El Paso, TX 79905 Rosy Sandoval
                          [phone] Recruiting 010201.
VIRGINIA                  Infectious Disease Consultants 10721 Main St
                          Fairfax, VA 22030 Jan Calco [phone]
                          Recruiting 010201.
VIRGINIA                  Infectious Disease Physicians Inc 3289
                          Woodburn Rd Annandale, VA 22003 Myrna Burns
                          [phone] Recruiting 010201.
WASHINGTON                Swedish Med Ctr 747 Broadway Seattle, WA
                          98122 Janice Price [phone] Recruiting
                          010201.

42
UNIQUE IDENTIFIER         NIH/01363
PROTOCOL ID NUMBERS       NIAID ACTG A5095
PROTOCOL TITLE            Phase III, Randomized, Double-Blind
                          Comparison of Three Protease
                          Inhibitor-Sparing Regimens for the Initial
                          Treatment of HIV Infection.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To compare the ability of 3 initial
                          protease inhibitor (PI)-sparing
                          antiretroviral regimens to suppress and
                          maintain HIV-1 RNA below 200 copies/ml (time
                          to failure). To determine the safety and
                          tolerability of the 3 initial PI-sparing
                          regimens.
GENERAL DESCRIPTION       RATIONALE: Current treatment guidelines
                          recommend combination regimens of 2
                          nucleoside analogues with either a PI or a
                          nonnucleoside reverse transcriptase inhibitor
                          (NNRTI) as the preferred therapy for the
                          initial treatment of HIV infection. However,
                          the efficacy of current regimens is limited
                          by their complexity, pharmacokinetic
                          characteristics, short- and long-term side
                          effects, and drug-resistance profiles at the
                          time of virologic failure. Consequently, the
                          identification of new initial regimens that
                          are simpler, better tolerated, preserve
                          treatment options in the event of virologic
                          failure, and improve on antiretroviral
                          potency is needed. In addition, recent
                          concern over the long-term toxicities of PIs
                          and the extensive cross-resistance among the
                          available PIs have led to the testing of
                          PI-sparing regimens.
GENERAL DESCRIPTION       METHODOLOGY: Step 1: Patients are randomly
                          selected to receive 1 of 3 blinded treatment
                          regimens: abacavir (ABC)/lamivudine
                          (3TC)/zidovudine (ZDV)/efavirenz (EFV),
                          ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with
                          confirmed virologic failure on Step 1 and
                          confirmed plasma HIV RNA levels of 10,000
                          copies/ml or greater must register to Step 2.
                          Patients with confirmed virologic failure on
                          Step 1 and plasma HIV RNA under 10,000
                          copies/ml may remain on Step 1 or register to
                          Step 2. Step 2: Step 2 is open label.
                          Regimens include 2 nucleoside reverse
                          transcriptase inhibitors (NRTIs) in
                          combination with either EFV or BMS-232632.
                          Based on genotypic resistance results, the
                          NRTI combination may be a fixed-dose
                          combination of 3TC/ZDV or 2 of the following:
                          ZDV, didanosine (ddI), 3TC, stavudine (d4T),
                          and ABC; however, the ZDV/d4T combination is
                          not permitted. Clinical assessments and
                          laboratory evaluations are done at entry, at
                          Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then
                          every 8 weeks thereafter for the duration of
                          the study. Evaluations are also required when
                          a protocol-allowed drug substitution is made.
                          In addition, 2 substudies are being
                          conducted: a neurology substudy for efavirenz
                          and a pharmacology substudy for BMS-232632.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy, Drug
                          safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 1125 patients. 375 per arm
                          to be accrued over approximately 66 weeks.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Patients will
                          be followed for 96 weeks beyond enrollment of
                          the last patient.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 183/1125 010731.
PROTOCOL DETAILS          STUDY DURATION: Approximately 3 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 49
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001222)
PROTOCOL DETAILS          DISEASE STUDIED: HIV InfectionsS
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Open Label; Random
                          Allocation; Single-Blind Method
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA by RT-PCR or bDNA,
                          or a second antibody test by a method other
                          than ELISA at any time prior to study entry.
                          2. Plasma HIV-1 RNA of at least 400 copies/ml
                          as measured by the Roche Amplicor or the
                          UltraSensitive HIV-1 Monitor assay (Roche
                          Molecular Systems) and performed within 90
                          days of study entry by any laboratory
                          certified for the assay. 3. A negative serum
                          or urine beta-HCG pregnancy test performed
                          within 48 hours before initiating the
                          protocol-specified medication(s), for women
                          of reproductive potential. 4. Consent of
                          parent or guardian if under 18 years of age.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 40000 /microL Within 30
                          days prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN ULN (Upper Limit of
                          Normal), within 30 days prior to study entry.
PATIENT INCLUSION CRIT.   OTHER: Serum lipase <= 1.5 x ULN within 30
                          days prior to study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test Abstinence
                          or two effective methods of birth control /
                          contraception during the study and for 90
                          days after.
PATIENT INCLUSION CRIT.   WEIGHT: Included: Weight of 40 kg or greater.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Alternative
                          therapies, such as acupuncture and
                          visualization techniques.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii
                          pneumonia for all patients having a CD4 cell
                          count of 200 cells/mm3 or less. 2. Topical
                          and oral antifungal agents, except for oral
                          ketoconazole and itraconazole. 3. Treatment,
                          maintenance, or chemoprophylaxis with
                          approved agents for opportunistic infections
                          as clinically indicated. 4. All antibiotics
                          as clinically indicated. Macrolide
                          antibiotics other than clarithromycin should
                          be used when possible. 5. Systemic
                          corticosteroid use for up to 21 days as
                          medically indicated; chronic systemic
                          corticosteroid use is not permitted, unless
                          it is within physiologic replacement levels.
                          The protocol chair or co-chair(s) must be
                          contacted in these instances. 6. Recombinant
                          erythropoietin, granulocyte
                          colony-stimulating factor, and
                          granulocyte-macrophage colony-stimulating
                          factor as medically indicated. 7. Regularly
                          prescribed medications, such as antipyretics,
                          analgesics, allergy medications,
                          antidepressants, sleep medications, oral
                          contraceptives, megestrol acetate,
                          testosterone, or any other medications as
                          medically indicated. 8. Sildenafil citrate.
                          Caution should be used in the concomitant use
                          of this drug with NNRTIs and PIs as there is
                          a potential for drug interaction. In the
                          event that a patient is prescribed sildenafil
                          citrate, a reduced dose of 25 mg is
                          suggested. 9. Alternative therapies, such as
                          vitamins. Herbal medications should be
                          avoided. 10. Systemic cytotoxic chemotherapy.
                          Allowed with caution: 1. Concomitant use of
                          statins, other than lovastatin or
                          simvastatin, with PIs. Note: There is a
                          potential for drug interaction with NNRTIs.
                          2. Alcohol consumption, as it may exacerbate
                          CNS symptoms of EFV. 3. Medications that
                          potentially interact with EFV, NVP, and/or
                          BMS-232632, including: alprazolam,
                          atorvastatin, amitriptyline, bupropion,
                          carbamazepine, cerivastatin,
                          chlorpheniramine, chlorpromazine,
                          chlorzoxazone, cimetidine, clarithromycin,
                          clofibrate, clorazepate, clozapine, codeine,
                          cyclosporine, desipramine, diazepam and other
                          benzodi
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: Any
                          previous known hypersensitivity to components
                          of the study drug formulations.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current substance
                          abuse that could compromise compliance with
                          the study medication, at the discretion of
                          the local investigator.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any prior
                          antiretroviral therapy. 2. Any
                          immunomodulator, HIV vaccine, or
                          investigational therapy within 30 days prior
                          to study entry. 3. Any other vaccination
                          within 30 days prior to study entry. 4. Acute
                          therapy, for serious infection or other
                          serious medical illnesses that are
                          potentially life threatening and require
                          systemic therapy and/or hospitalization,
                          within 14 days prior to study entry. 5.
                          Treatment within 14 days prior to study entry
                          with any of the following: amiodarone,
                          astemizole, bepridil, cisapride, ergot or
                          ergot derivatives, itraconazole, systemic
                          ketoconazole, midazolam, propoxyphene,
                          quinidine, rifabutin, rifampin, terfenadine,
                          thalidomide, triazolam, or St. John's wort.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. All other
                          antiretroviral therapies, other than study
                          medications. 2. All other investigational
                          drugs, unless specified in permitted
                          medications. 3. Amiodarone, astemizole,
                          bepridil, cisapride, ergot alkaloids or drugs
                          containing derivatives of ergot alkaloids,
                          St. John's wort, itraconazole, ketoconazole,
                          midazolam, propoxyphene, quinidine,
                          rifabutin, rifampin, terfenadine,
                          thalidomide, triazolam, and vincristine. 4.
                          Chronic systemic corticosteroid use, unless
                          it is within physiologic replacement levels.
                          5. Concomitant use of lovastatin or
                          simvastatin with PIs. Avoided: Herbal
                          medications.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Pneumocystis
                          carinii pneumonia, if not clinically stable
                          or if acute therapy not completed at least 7
                          days prior to study entry. 2. Other serious
                          infection or serious medical illness, such as
                          disseminated Mycobacterium avium complex, if
                          not clinically stable or if chronic
                          (maintenance) therapy of at least 14 days has
                          not been completed prior to study entry. 3.
                          Other infections or medical illnesses, if not
                          clinically stable or if therapy not completed
                          prior to study entry. Oral and vaginal
                          candidiasis, mucocutaneous herpes simplex,
                          and other minor illnesses (in the opinion of
                          the investigator) have no restriction. 4. Any
                          condition which, in the opinion of the
                          investigator, would compromise the patient's
                          ability to participate in the study. 5.
                          Malignancy requiring systemic chemotherapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0325
                          Lamivudine/Zidovudine/Abacavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0285  BMS-232632
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0257  Lamivudine/Zidovudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0126  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0004  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0269  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0043  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 8  DRG-0116  Stavudine
SUBSTANCE IDENTIFICATION  Drug 9  DRG-0016  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 10: DRG-031  Didanosine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Step 1, Arm A or B:
                          One tablet (ABC 300 mg/3TC 150 mg/Z300 mg)
                          bid. Drug 2: Step 1, Arm C or Step 2 option:
                          One tablet (3TC 150 mg/300 mg) bid. Drug 3:
                          Step 1, Arm A or B: 300 mg bid, administered
                          individualdose reduction of ZDV or
                          substitution of ZDV is required. Step 2
                          option: 300 mg bid. Drug 4: Step 1, Arm A, B,
                          or C: 150 mg bid, administered individually
                          if dose reduction of ZDV or substitution of
                          ZDV anABC is required. Step 2 option: 150 mg
                          bid. Drug 5: Step 1, Arm A, B, or C: 200 to
                          300 mg bid, administeredindividually if dose
                          reduction or substitution of ABC is
                          requirStep 2 option: 200 to 300 mg bid. Drug
                          6: Step 1, Arm A or C, or Step 2, Arm D: 600
                          mg qd. Drug 7: Step 1, Arm A, B, or C, as
                          substitution for ZDV: 20 to bid if 60 kg or
                          more; 15 to 30 mg bid if less than 60 kg.
                          Step 2 option: 20 to 40 mg bid if 60 kg or
                          more; 15 to 30 mg biless than 60 kg. Drug 8:
                          Step 1, Arm A or C, or Step 2, Arm D, as
                          substitution fEFV: 200 mg qd x 14 d, then 200
                          mg bid. Drug 9: Step 1, Arm A or B, as
                          substitution for ABC: 125 to 200bid if 60 kg
                          or more; 75 to 125 mg bid if less than 60 kg.
                          Step 2 option: 125 to 200 mg bid if 60 kg or
                          more; 75 to 125 mgif less than 60 kg. For the
                          enteric-coated formulation, tablets may be
                          taken once di.e., 250 to 400 mg qd if 60 kg
                          or more; 125 to 250 mg qd if lethan 60 kg.
                          Drug 10: Step 2, Arm E: 200 to 400 mg qd
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: ABC 600 mg/3TC 300
                          mg/ZDV 600 mg. Drug 2: 3TC 300 mg/ZDV 600 mg.
                          Drug 3: 600 mg. Drug 4: 300 mg. Drug 5: 400
                          mg to 600 mg. Drug 6: 600 mg. Drug 7: 40 to
                          80 mg if 60 kg or more; 30 to 60 mg if less
                          than Drug 8: 200 mg for 14 days, then 400 mg.
                          Drug 9: 125 mg to 400 mg. Drug 10: 200 to 400
                          mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral. Drug 5: Oral.
                          Drug 6: Oral. Drug 7: Oral. Drug 8: Oral.
                          Drug 9: Oral. Drug 10: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Patients continue on the
                          treatment until 96 weeks after the last
                          patient is enrolled.
OTHER TREATMENT INFO.     END POINT: 1. The primary efficacy endpoint
                          of the study is the time from randomization
                          to first virologic failure (2 successive
                          measurements of HIV-1 RNA of 200 copies/ml or
                          greater). 2. The safety of the Step 1
                          regimens will be assessed according to the
                          time from the start of study treatment to the
                          first development of Grade 3 or Grade 4 sign,
                          symptom, or laboratory abnormality that is at
                          least 1 grade higher than baseline. All new
                          adverse events occurring after treatment
                          dispensation and up to 56 days after the date
                          of the last dose of Step 1 study medications,
                          or until initiation of new medications,
                          whichever occurs first, will be included. 3.
                          The tolerability of the Step 1 regimens will
                          be assessed according to the time from start
                          of study treatment to the discontinuation of
                          either ABC or EFV, whichever occurs first.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Drug-related
                          toxicity. 2. Development of an exclusionary
                          condition. 3. Requirement for excluded
                          concomitant medications. 4. Failure to attend
                          3 consecutive clinic visits. 5. Request by
                          the patient to withdraw. 6. Request of the
                          primary care provider if she/he thinks the
                          study is no longer in the best interest of
                          the patient. 7. Clinical reasons believed
                          life threatening by the physician, even if
                          not addressed in the toxicity management of
                          the protocol. 8. Patient judged by the
                          investigator to be at significant risk of
                          failing to comply with the provisions of the
                          protocol as to cause harm to self or
                          seriously interfere with the validity of the
                          study results. 9. At the discretion of the
                          Adult AIDS Clinical Trials Group, Food and
                          Drug Administration, National Institute of
                          Allergy and Infectious Diseases,
                          investigator, or pharmaceutical sponsor(s).
OTHER TREATMENT INFO.     MODIFICATION: Dosage reductions are permitted
                          for toxicity management of ZDV, ddI, d4T, and
                          BMS-232632, in accordance with protocol
                          guidelines.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Kaiser Permanente LAMC 1505 N Edgemont St /
                          Second Floor Los Angeles, CA 90027 Gloria
                          Roman [phone] Recruiting 010529.
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010406.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010228.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010612.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010702.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 010522.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 010406.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Mario Guerrerro
                          [phone] Recruiting 010423.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 010522.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010405.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010406.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Ericka Patrick [phone] Recruiting
                          010717.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010528.
IOWA                      Univ of Iowa Hosp and Clinic 200 Hawkins Dr
                          Iowa City, IA 52242 Julie Katseres
                          [phone] Recruiting 010621.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010528.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010423.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010323.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010323.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010323.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 010418.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010423.
NORTH CAROLINA            Moses H Cone Memorial Hosp 1200 North Elm St
                          Greensboro, NC 27401 Lisa Dasnoit
                          [phone] Recruiting 010405.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 010323.
NEBRASKA                  Univ of Nebraska Med Ctr 985130 Nebraska Med
                          Ctr Omaha, NE 681985130 Frances Van Meter
                          [phone] Recruiting 010314.
NEW YORK                  St Mary's Hosp (Univ of Rochester/Infectious
                          Diseases) 601 Elmwood Ave Rochester, NY 14642
                          Carol Greisberger [phone] Recruiting
                          010621.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010502.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010423.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 010712.
NEW YORK                  Aaron Diamond AIDS Rsch Ctr / Rockefeller
                          Univ 1230 York Ave New York, NY 10021 Arlene
                          Hurley [phone] Recruiting 010323.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Rachele Cruz
                          [phone] Recruiting 010502.
NEW YORK                  Cornell Clinical Trials Unit 119 West 24th St
                          / Ground Floor New York, NY 10011 Todd
                          Stroberg [phone] Recruiting 010418.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 010318.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010418.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Valery Hughes [phone]
                          Recruiting 010418.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010418.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010405.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 010502.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 010621.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 010508.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] Recruiting 010702.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010314.
PENNSYLVANIA              Philadelphia Veterans Administration Med Ctr
                          536 Johnson Pavilion Philadelphia, PA 19104
                          Joseph Quinn [phone] Recruiting 010605.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 010405.
RHODE ISLAND              Brown Univ / Miriam Hosp 164 Summit Ave /
                          Immunology Ctr Providence, RI 02906 Joan
                          Gormley [phone] Recruiting 010405.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 010405.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 010612.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Carrie Derkowski [phone]
                          Recruiting 010628.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Chip
                          Lohner [phone] Recruiting 010410.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010627.

43
UNIQUE IDENTIFIER         NIH/01362
PROTOCOL ID NUMBERS       NIAID ACTG P1013
PROTOCOL TITLE            A Phase I/II Trial of Ritonavir and Indinavir
                          in Children Failing Other Antiretroviral
                          Therapy.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
GENERAL DESCRIPTION       PURPOSE: Stage A: To determine doses of
                          ritonavir (RTV) and indinavir (IDV), in 2
                          dosing ratios, that are safe, tolerable, and
                          achieve similar systemic exposure shown to be
                          effective in adults. Stages A and B: To
                          assess the pharmacokinetics, safety, and
                          tolerability of the 2 combination regimens in
                          pediatric HIV-infected patients who have
                          failed other antiretroviral therapies. To
                          assess the antiretroviral activity and the
                          relationship of the pharmacokinetic profiles
                          of the 2 combinations of RTV and IDV to the
                          degree and durability of viral suppression.
GENERAL DESCRIPTION       RATIONALE: Combination regimens of RTV and
                          IDV in adults offer the benefit of 2 potent
                          antiretroviral agents, convenience of
                          twice-daily dosing, unrestricted timing of
                          meals, and fewer renal complications. There
                          are limited, largely anecdotal, data from
                          children suggesting that initial virological
                          response can also be attained in children
                          given IDV with RTV, but there are not
                          sufficient pharmacokinetic data to define
                          appropriate dose regimens. This study
                          evaluates the clinical feasibility of this
                          regimen for children.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified for
                          Stage A on the basis of age/Tanner stage and
                          ability to swallow intact capsules. Within
                          Stage A, patients are randomized to either
                          Balanced Dose or Low Dose RTV treatment arms.
                          Patients in the Balanced Dose Arm receive RTV
                          and IDV in approximately equal doses. The Low
                          Dose RTV Arm receives a dosing ratio of
                          RTV:IDV of approximately 1:3. Stage A aims to
                          find appropriate doses of RTV:IDV through
                          intensive pharmacokinetic analysis done at
                          Week 4 (or 2 weeks after a stable dose of
                          study drugs has been reached) and Week 16.
                          Stage B opens to enrollment after the best
                          doses have been determined in Stage A based
                          on the following: 1) safety and tolerability
                          for patients treated for 8 or more weeks and
                          2) pharmacokinetics criteria. For Stage B,
                          patients are randomized after real-time
                          genotypic screening and stratified by
                          age/Tanner stage and use of a new nucleoside
                          reverse transcriptase inhibitor (NRTI). Stage
                          B tests the virologic activity, safety, and
                          tolerability of the dose selected for each
                          treatment arm in Stage A. Patients without
                          significant genotypic resistance are enrolled
                          into each treatment arm. Other patients with
                          significant genotypic resistance to RTV or
                          IDV are also enrolled. Laboratory and
                          clinical evaluations at scheduled clinic
                          visits determine HIV RNA levels and
                          pharmacology, safety, and immunologic
                          parameters.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Optimal dose of combination
                          drug therapy, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 116 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 96 weeks, with
                          an optional 48-week extension if virologic
                          criteria are met.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 8/116 010724.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 24
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001213)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1013
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Dose-Response Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV infection as demonstrated by 2
                          positive viral tests on peripheral blood or
                          CSF (DNA or RNA PCR, HIV co-culture or
                          neutralizable p24 antigen), 1 of which must
                          be either a peripheral blood HIV co-culture
                          or a peripheral blood HIV DNA PCR. If patient
                          is more than 18 months of age at the time of
                          testing, evidence of infection by at least 2
                          positive HIV antibody tests is acceptable. 2.
                          Have HIV RNA level above 10,000 copies/ml
                          within 30 days prior to entry. 3. Have
                          evidence of antiretroviral therapy failure
                          (defined as: 1) more than 0.75 log rebound
                          from virologic nadir and above 10,000
                          copies/ml after more than 16 weeks of
                          combination therapy or 2) less than a 1 log
                          decrease of viral load after more than 16
                          weeks combination therapy) while receiving
                          more than 16 weeks of unchanged, continuous,
                          combination antiretroviral therapy. 4. Have a
                          body surface area greater than 0.48 m2. 5.
                          Have signed consent of parent or legal
                          guardian.
PATIENT INCLUSION CRIT.   PLATELET COUNT: 25000 to 49000 /mm3 Grade 3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test Negative pregnancy
                          test within 30 days of study entry Abstinence
                          or effective (approved) method of birth
                          control.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: IDV or RTV
                          separately or sequentially.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. NRTIs as
                          selected by the primary care provider prior
                          to a patient's randomization on study. At
                          least 1 NRTI is required by this protocol and
                          additional NRTIs may be prescribed at the
                          treating physician's discretion. All NRTI
                          therapy must be determined prior to a
                          patient's randomization on study and if new
                          NRTI is started it must be started on the
                          same day as the first doses of study drugs.
                          2. IVIG. Required: At least 1 NRTI.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 02
                          years less than or equal to 17 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Excluded: Failure
                          of HIV virus to be amplified for
                          determination of genotypic resistance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Receipt of IDV
                          and RTV in combination. 2. Glucocorticoids at
                          systemic doses above 1 mg/kg/day for more
                          than 14 days at entry. 3. Immunomodulatory
                          therapy other than IVIG within 3 months of
                          study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Protease
                          inhibitors not prescribed by this study. 2.
                          Nonnucleoside reverse transcriptase
                          inhibitors. 3. Hydroxyurea. 4. All
                          investigational drugs. 5. HIV vaccines. 6.
                          Systemic cytotoxic chemotherapy. 7.
                          Medications known to yield clinically
                          significant interactions with cytochrome P450
                          substrates.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Active malignancy
                          requiring chemotherapy. 2. Significant
                          genotypic resistance to IDV or RTV at
                          screening, for Stage A only. Determination of
                          significant resistance will be made at
                          designated virology laboratory. 3. Current
                          Grade 3 to 4 clinical or laboratory
                          abnormality at screening as defined by the
                          DAIDS standard toxicity tables with the
                          following exceptions: Grade 3 ANC (greater
                          than 250 to 399/mm3) and Grade 3 platelet
                          count (greater than 25,000 to 49,000/mm3)
                          will be allowed to enter. 4. Inability to be
                          followed by a PACTG center for the duration
                          of this trial.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Stage A: Balanced
                          Dose and Low Dose Arms, 350 mg/m2 q12Drug 2:
                          Stage A: Balanced Dose Arm: 300 mg/m2 q12h.
                          Low Dose Arm: 125 mg/m2 q12h
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Stage A: Balanced Dose
                          and Low Dose Arms, 700 mg/m2. Drug 2: Stage
                          A: Balanced Dose Arm: 600 mg/m2. Low Dose
                          Arm: 250 mg/m2
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 96 weeks.
OTHER TREATMENT INFO.     END POINT: Life-threatening adverse events;
                          dose-limiting toxicity as defined in the
                          protocol; a log drop of 0.75 from entry HIV
                          RNA; and a confirmed rebound to within 0.75
                          log below entry HIV RNA.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. The mean of the HIV
                          RNA reduction at Weeks 12 and 16 is less than
                          0.75 log from the entry measures. 2. HIV RNA
                          rebounds to within 0.75 log of entry
                          confirmed by 2 specimens 4 weeks apart
                          anytime after the Week 16 visit. 3. Drug
                          toxicity experienced by Stage A patients
                          requiring dose reduction of IDV. 4. Refusal
                          of further treatment and/or follow-up
                          evaluations by patient or legal guardian. 5.
                          Investigator determination that further
                          participation would be detrimental to the
                          patient's health or well-being. 6. Patient
                          failure to comply with the study requirements
                          so as to cause harm to self or seriously
                          interfere with the validity of the study
                          results. 7. Patient requirement for treatment
                          with disallowed medications. 8. Drug toxicity
                          as defined in the protocol. 9. Pregnancy.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 010627.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 010419.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 010522.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 010522.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          010621.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 010419.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          010627.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699
                          Margaret Cowie [phone] Recruiting
                          010502.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Kirk
                          Bertelsen [phone] Recruiting 010502.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 010502.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 010730.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 010522.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Lisa Cerrachio
                          [phone] Recruiting 010717.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 010419.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 010612.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010731.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 010419.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 010702.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 010517.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 010419.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Sylvia Davila Nieves [phone] Recruiting
                          010419.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Felipe Pabon [phone]
                          Recruiting 010419.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Jill Utech [phone] Recruiting
                          010509.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 010522.

44
UNIQUE IDENTIFIER         NIH/01360
PROTOCOL ID NUMBERS       NIAID ACTG A5086
PROTOCOL TITLE            Evaluation of the Role of Temporary Cessation
                          of Antiretroviral Treatment and Resistance
                          Testing-Based Selection of Antiretroviral
                          Drugs in the Virologic Response to Salvage
                          Therapy for Heavily Treatment-Experienced
                          HIV-Infected Individuals Failing Current
                          Antiretroviral Therapy.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare the proportion of
                          patients in each arm with plasma HIV-1 RNA
                          levels below 400 copies/ml at Week 48 after
                          randomization.
GENERAL DESCRIPTION       RATIONALE: Virologic failure occurs in a
                          large proportion of individuals receiving
                          treatment with combination antiretroviral
                          therapy. Studies suggest that treatment
                          interruption prior to initiation of a
                          multiple-drug rescue regimen may improve
                          virologic response in individuals who have
                          failed several prior antiretroviral regimens.
                          Other studies suggest there is a virologic
                          benefit derived from using genotypic or
                          phenotypic resistance testing in selecting
                          salvage therapy regimens for patients failing
                          antiretroviral therapy. This study tests the
                          hypothesis that salvage regimens selected on
                          the basis of HIV-1 resistance genotype,
                          phenotype, and treatment history will be more
                          effective if there is a period of treatment
                          interruption before initiating that regimen.
GENERAL DESCRIPTION       METHODOLOGY: Patients continue their
                          antiretroviral therapy until randomization.
                          Based on the results of the pre-entry
                          genotype and phenotype tests and treatment
                          history, an individualized salvage therapy
                          regimen (not provided by the study) is
                          selected by the site investigator(s).
                          Additionally, patients start or continue
                          maintenance therapy (not provided by the
                          study) for opportunistic infections (OIs).
                          Patients are randomized to 1 of 2 treatment
                          arms. In Arm A, patients have antiretroviral
                          treatment interruption for a period of 16
                          weeks (Step 1), followed by initiation of the
                          salvage therapy regimen (Step 2). In Arm B,
                          patients switch immediately to the salvage
                          therapy regimen. [AS PER AMENDMENT 2/15/01:
                          Patients who become pregnant during Step 1 of
                          Arm A must be advised to begin their
                          selected, individualized salvage therapy
                          regimen or a modified salvage regimen.
                          Patients who become pregnant during Step 2 of
                          Arm A or Arm B have therapy evaluated and
                          undergo any changes required by their
                          pregnancy.] Patients in both arms are
                          monitored for plasma HIV-1 RNA levels, CD4+
                          and CD8+ cell counts, and HIV drug resistance
                          genotypes and phenotypes for a duration of 64
                          weeks from randomization. Patients on Arm A
                          are also monitored for immune reactivation by
                          measurement of T-cell subsets and plasma
                          cytokines during treatment interruption.
                          Patients may participate in a virology
                          substudy (A5100s) and an immunology substudy
                          (A5104s).
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Strategy determination.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 220 patients. 110 per arm.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 64 weeks from
                          randomization.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 3/220 010629.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 21
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010215)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5086. Substudy
                          AACTG A5100s. Substudy AACTG A5104s
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV infection as documented by any
                          licensed ELISA test and confirmed by Western
                          blot, HIV culture, HIV antigen, plasma HIV-1
                          RNA, or a second antibody test by a method
                          other than ELISA at any time before study
                          entry. 2. Have a high likelihood of
                          multidrug-resistant HIV-1 in plasma (i.e.,
                          HIV-1 that has resistance to at least 1 drug
                          from each of the 3 approved drug classes),
                          and defined as both: 1) extensive prior
                          exposure to all 3 classes of antiretroviral
                          drugs (at least 2 NRTIs for at least 12
                          months, at least 2 PIs each for at least 6
                          months [RTV 100 or 200 mg bid plus 1 other PI
                          is considered 1 PI for the purposes of this
                          study], and 1 or more NNRTIs for at least 3
                          months); and 2) history of virologic failure,
                          in the opinion of the clinician, of an
                          antiretroviral therapy regimen that predates
                          the current failing regimen and for which
                          treatment was not discontinued because of
                          toxicity. 3. Have virologic failure on
                          current potent antiretroviral therapy, as
                          defined by a detectable plasma HIV-1 RNA
                          level of at least 10,000 copies/ml (as
                          measured in a Roche-certified laboratory)
                          within 42 days prior to study entry. Patients
                          must have been on the failing regimen for at
                          least 8 weeks prior to entry and for at least
                          4 weeks prior to performance of screening
                          genotypic and phenotypic resistance testing;
                          patients should continue this regimen to the
                          time of entry unless clinically
                          contraindicated. 4. Have had screening
                          results of genotypic and phenotypic analyses
                          returned to the site from the Virco
                          laboratory. 5. Have had a salvage therapy
                          regimen selected by the site investigator. 6.
                          Have a CD4+ T-lymphocyte count of at least
                          150 cells/microL within 42 days prior to
                          entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 150 cells/microL
                          Within 42 days prior to study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test Pregnancy allowed
                          under certain conditions. See 'Inclusion -
                          General Criteria' section.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Potent
                          antiretroviral therapy, defined as the use of
                          at least 3 anti-HIV drugs in combination.
                          Note: For purposes of this study, low-dose
                          ritonavir (100 to 200 mg bid) with 1 other PI
                          is counted as a single PI.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Inability to have a potent antiretroviral
                          therapy regimen (as defined in the protocol)
                          constructed based on medication history
                          because of unacceptable drug intolerance or
                          toxicity from available antiretroviral drugs.
                          2. Treatment interruption of more than 4
                          weeks in the past 6 months.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: The following
                          immunomodulating agents, within 14 days prior
                          to entry: erythropoietin; G-CSF; GM-CSF;
                          interleukins; and therapeutic HIV vaccines.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Systemic
                          chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Malignancy
                          requiring treatment with systemic
                          chemotherapy or radiation therapy. 2.
                          Expectation of being available for less than
                          1 year.
OTHER TREATMENT INFO.     END POINT: Proportion of patients in each arm
                          with plasma HIV-1 RNA below 400 copies/ml at
                          Week 48 after randomization.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Requirement for
                          systemic chemotherapy or radiation therapy
                          for treatment of a malignancy. 2. Patient
                          failure, without reasonable cause, to attend
                          3 consecutive study visits. 3. Patient
                          request. 4. Discretion of the investigator.
                          5. Discretion of the protocol team, or DAIDS.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010314.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 010522.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010712.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 010528.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 010522.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010405.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010502.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010405.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010508.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010405.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010405.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010405.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 010502.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010528.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Rachele Cruz
                          [phone] Recruiting 010517.
NEW YORK                  Cornell Clinical Trials Unit 119 West 24th St
                          / Ground Floor New York, NY 10011 Todd
                          Stroberg [phone] Recruiting 010528.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 010502.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Valery Hughes [phone]
                          Recruiting 010528.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010314.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 010612.
TEXAS                     Children's Med Ctr of Dallas 1935 Motor St
                          Dallas, TX 75235 Dewan Perry [phone]
                          Recruiting 010517.

45
UNIQUE IDENTIFIER         FDA/01358
PROTOCOL ID NUMBERS       FDA 283G
PROTOCOL TITLE            US Expanded Access Program of Tenofovir
                          Disoproxil Fumarate in the Treatment of HIV-1
                          Infected Patients Who Have Limited Treatment
                          Options.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: The primary objective of this study
                          is to make tenofovir disoproxil fumarate (DF)
                          available to HIV-infected patients who have
                          failed commercially available antiretroviral
                          treatment regimens, have limited treatment
                          options, and are at risk for disease
                          progression, prior to the commercial
                          availability of this antiretroviral agent.
                          Methodology: Patients receive daily doses of
                          tenofovir DF.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive daily doses of
                          tenofovir DF.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010727)
PROTOCOL DETAILS          STUDY INTENT: Expanded access.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Patients
                          continue on the study until
                          treatment-limiting toxicity, patient is lost
                          to follow-up, voluntary withdrawal, or
                          termination of the program by Gilead
                          Sciences.
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001117)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: GS-00-955
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Expanded Access
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented laboratory diagnosis of
                          HIV-1 infection (positive ELISA HIV-1
                          antibody test confirmed by Western blot, p24
                          assay, HIV-1 RNA, or culture). 2. Plasma
                          HIV-1 RNA levels of 10,000 copies/ml or more
                          by PCR (values obtained within previous 2
                          months are acceptable). 3. A CD4 count of 100
                          cells/mm3 or less within the previous 2
                          months. Patients with CD4 count greater than
                          100 and up to and including 200 cells/mm3,
                          with documented evidence of an AIDS-defining
                          opportunistic infection within the past 90
                          days, will also be eligible. 4. Treatment
                          failure with at least 2 protease inhibitors
                          (PIs) or with at least 1 PI plus a
                          nonnucleoside reverse transcriptase inhibitor
                          (NNRTI). 5. A lack of viable combinations of
                          antiretroviral agents with available drugs
                          based on current treatment guidelines and the
                          patient's previous antiretroviral use. 6.
                          Negative serum pregnancy test.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 100 cells/mm3 Within
                          the previous 2 months. Patients with CD4 >
                          100 and <= 200 cells/mm3 and documented
                          evidence of an AIDS-defining opportunistic
                          infection within the past 90 days are
                          eligible.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl <= 3.0 mg/dl for
                          patients with indinavir-associated
                          hyperbilirubinemia.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Serum phosphorous >= 2.2 mg/dl. Serum
                          amylase <= 1.5 x ULN or greater than 1.5 x
                          ULN if serum lipase is <= 1.5 x ULN (Upper
                          Limit of Normal).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 30 days after Not pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of clinically significant renal or
                          bone disease.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current alcohol or
                          substance abuse judged by the investigator to
                          potentially interfere with patient
                          compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Adefovir
                          dipivoxil (until pharmacokinetic data are
                          available to guide dosing), if taken within 7
                          days of study enrollment. 2. Nephrotoxic
                          agents, such as but not limited to:
                          aminoglycoside antibiotics, cidofovir,
                          foscarnet, intravenous (IV) amphotericin B,
                          IV pentamidine, IV vancomycin, and other
                          agents with significant nephrotoxic
                          potential, if taken within 7 days of study
                          enrollment. 3. Chemotherapeutic agents with
                          nephrotoxic potential (e.g., cisplatin), if
                          taken within 7 days of study enrollment. 4.
                          Prior therapy that, in the opinion of the
                          investigator, would make the patient
                          unsuitable for the program or unable to
                          comply with the dosing requirements.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Adefovir
                          dipivoxil (until pharmacokinetic data are
                          available to guide dosing). 2. Nephrotoxic
                          agents, such as but not limited to:
                          aminoglycoside antibiotics, cidofovir,
                          foscarnet, intravenous (IV) amphotericin B,
                          IV pentamidine, IV vancomycin, and other
                          agents with significant nephrotoxic
                          potential. 3. Chemotherapeutic agents with
                          nephrotoxic potential (e.g., cisplatin).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Any
                          clinical condition that, in the opinion of
                          the investigator, would make the patient
                          unsuitable for the program or unable to
                          comply with the dosing requirements. 2. Renal
                          dysfunction. 3. Bone Disease.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0290  Tenofovir disoproxil
                          fumarate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 300 mg once daily
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 300 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Patients continue on the
                          treatment until treatment-limiting toxicity,
                          voluntary withdrawal, or termination of the
                          program by Gilead Sciences.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1.
                          Treatment-limiting toxicity. 2. Voluntary
                          withdrawal. 3. Termination of the program by
                          Gilead Sciences.
SUPPORTING AGENCY         Gilead Sciences Inc.
LAST REVISION DATE        20010727

46
UNIQUE IDENTIFIER         NIH/01357
PROTOCOL ID NUMBERS       NIAID HIVNET 026
PROTOCOL TITLE            A Multisite Phase II Clinical Trial to
                          Evaluate the Immunogenicity and Safety of
                          ALVAC-HIV vCP1452 Alone and Combined with MN
                          rgp120 in Brazil, Haiti, and Trinidad and
                          Tobago.
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Preventative HIV Vaccine
GENERAL DESCRIPTION       PURPOSE: To evaluate the immunogenicity and
                          confirm the safety of 2 vaccine regimens:
                          ALVAC-HIV vCP1452 combined with MN rgp120,
                          and ALVAC-HIV vCP1452 given alone. The
                          primary objectives related to immunogenicity
                          include: 1) evaluation of the net CD8+ CTL
                          response rate for each active treatment arm
                          and 2) comparisons of mean titers of
                          neutralizing antibodies to HIV-1 MN between
                          each active treatment arm and the placebo
                          arm. The primary objectives related to
                          evaluation of safety are: comparison of the
                          rates of severe systemic and rates of severe
                          local reactions for each of the active
                          treatment arms to the placebo arm.
GENERAL DESCRIPTION       RATIONALE: There is no cure for HIV infection
                          or AIDS in spite of recent advances in
                          antiviral therapy. Furthermore, drug therapy
                          is too expensive for most affected
                          populations. For this reason, there is a
                          commitment to the development of safe,
                          effective vaccines to prevent HIV infection
                          and AIDS worldwide. This study evaluates the
                          immunogenicity and safety of candidate HIV-1
                          vaccines, based on the canarypox vector
                          termed ALVAC, alone and combined with an MN
                          rgp120 product, at 3 international sites.
GENERAL DESCRIPTION       METHODOLOGY: Volunteers from Haiti, Brazil,
                          and Trinidad and Tobago are enrolled into 1
                          of 3 arms and followed for 18 months. Arm 1
                          volunteers receive ALVAC-HIV vCP1452 at 0, 1,
                          3, and 6 months. Arm 2 volunteers receive
                          ALVAC-HIV vCP1452 on the same schedule as Arm
                          1 and receive HIV-1 MN rgp120 subunit
                          simultaneously with the 3-month and 6-month
                          vaccine doses. Arm 3 volunteers receive a
                          placebo. Blood and urine samples are
                          collected for immunologic assays, virologic
                          determinations, pregnancy testing, and safety
                          assessments. Risk behavior and social harms
                          are assessed every 6 months during follow-up.
                          At all clinic visits volunteers receive
                          counseling on avoidance of HIV infection and
                          pregnancy. Participants are tested for HIV-1
                          every 3 to 6 months. Counseling and follow-up
                          for any needed medical care are provided.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Primary prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 120 patients. 40 per site:
                          30 immunogen, 10 control.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 18 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 24/120 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (990615)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: HVTN 026
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must:
                          1. Be recruited primarily from Projeto Praca
                          Onze, if from Brazil; be identified from
                          pools of individuals referred from the
                          GHESKIO and family planning clinics, if from
                          Haiti; or be identified from several sources,
                          including STD clinic attenders, if from
                          Trinidad or Tobago. 2. Have not acquired a
                          sexually transmitted disease (STD) in the
                          last 6 months (syphilis, gonorrhea, first
                          episode herpes, PID, trichomonas, chancroid,
                          chlamydia, lymphogranuloma venereum,
                          mucopurulent cervicitis, acute epididymitis,
                          acute proctitis, and nongonococcal
                          urethritis). 3. Have not had more than 1
                          sexual partner in the last 6 months. 4. Have
                          not injected drugs or used crack cocaine in
                          the last 6 months. 5. Not have exchanged sex
                          for money or drugs in the last 6 months. 6.
                          Be available for 18 months of follow-up. 7.
                          Have a normal history and physical
                          examination. 8. Be negative for hepatitis B
                          surface antigen. 9. Be negative for HTLV-1.
                          10. Be negative for RPR or FTA-ABS. 11. Be
                          negative for sickle screen (those with sickle
                          cell trait will be eligible). 12. Have
                          HIV-seronegativity ELISA and RNA PCR on
                          specimen obtained within 8 weeks of initial
                          immunization. 13. Have EBV-viable line (i.e.,
                          confirmed by the HIVNET Central Laboratory to
                          be mature enough to perform CTL assays) at
                          time of first immunization.
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 30 %.
PATIENT INCLUSION CRIT.   PLATELET COUNT: 125000 to 550000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN ULN (Upper Limit of
                          Normal). Institutional ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: White count >= 3,500 cells/mm3 and <=
                          15,000 cells/mm3 with normal differential or
                          approved by site physician. Total lymphocyte
                          count >= 800 cells/mm3. Normal urine dipstick
                          for protein, glucose, and blood (Trace
                          protein or 1+ is acceptable if creatinine is
                          normal).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 3 days of
                          initial drug administration Abstinence or
                          effective method of birth control /
                          contraception 1 month before and during the
                          study.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 60 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Volunteers with
                          the following prior conditions are excluded:
                          1. History of immunodeficiency, chronic
                          illness, malignancy, autoimmune disease, or
                          use of immunosuppressive medications.
                          Individuals with a history of cancer are
                          excluded unless there has been surgical
                          excision followed by a sufficient observation
                          period to give a reasonable assurance of
                          cure. 2. History of anaphylaxis or history of
                          other serious adverse reactions to vaccines.
                          3. History of serious allergic reaction to
                          any substance, requiring hospitalization or
                          emergent medical care (e.g., Stevens-Johnson
                          syndrome, bronchospasm, or hypotension).
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: 1. Injection of
                          drugs or use of crack cocaine in the last 6
                          months. 2. More than 1 sexual partner in the
                          last 6 months. 3. Exchange of sex for money
                          or drugs in the last 6 months.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Blood products or
                          immunoglobulin in the past 6 months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Live
                          attenuated vaccines within 60 days of planned
                          vaccination. Medically indicated subunit or
                          killed vaccines (e.g., influenza or
                          pneumococcal) are not exclusionary but should
                          be given at least 2 weeks away from HIV
                          immunizations. 2. Experimental agents within
                          30 days prior to planned vaccination. 3.
                          HIV-1 vaccines or placebo in a previous HIV
                          vaccine trial.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Medical or
                          psychiatric condition or occupational
                          responsibilities that preclude patient
                          compliance with the protocol. 2. Sexual
                          partner known to be HIV-infected unless
                          practicing abstinence or consistent latex
                          condom use for the last 6 months. 3. Sexual
                          partner known to be at high risk of HIV
                          infection (multiple sexual partners in the
                          last 6 months, injection drug or crack
                          cocaine use in the last 6 months, diagnosed
                          with STD in the last 6 months [syphilis,
                          gonorrhea, first episode herpes, PID,
                          trichomonas, chancroid, chlamydia,
                          lymphogranuloma venereum, mucopurulent
                          cervicitis, acute epididymitis, acute
                          proctitis, nongonococcal urethritis, or
                          hepatitis B]). 4. Active tuberculosis (TB).
                          Volunteers with a positive PPD and a chest
                          x-ray showing no evidence of active TB and
                          not requiring INH therapy are eligible. 5.
                          Allergy to egg products, thimerosal, or
                          neomycin.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0270  MN rgp120/HIV-1
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Groups A and B: 1
                          ml, Days 0, 28, 84, and 168. Drug 2: Arm A: 1
                          ml, Days 84 and 168
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Intramuscular
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 months.
OTHER TREATMENT INFO.     END POINT: Safety (occurrence of severe
                          systemic and severe local reactions); and
                          immunogenicity (evaluated by CTL reactivity
                          to HIV-1 gag, and env proteins; and induction
                          of neutralizing antibody to HI-1 MN).
OTHER TREATMENT INFO.     DISCONTINUE: Participants may be discontinued
                          for the following reasons: 1. HIV infection.
                          2. Pregnancy. 3. Grade IV systemic event
                          classified as probably or definitely
                          associated with immunization. 4. Grade IV
                          local adverse event classified as probably
                          or definitely associated with immunization.
                          5. Type 1 hypersensitivity associated with
                          immunization. 6. Intercurrent illness that is
                          not expected to resolve prior to the next
                          scheduled immunization. Participants who are
                          terminated from the immunization schedule
                          will remain in study follow-up as scheduled.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
OTHER                     Med Research Foundation of Trinidad 7 Queens
                          Park East Port of Spain, Courtenay
                          Bartholomew [phone] Recruiting 010119.
OTHER                     Institut Natl de Laboratoire et de Recherches
                          Cornell-GHESKIO / 33 Blvd Harry Truman
                          Port-au-Prince, Jean Pape (509)220-031
                          Recruiting 010119.
OTHER                     Hosp Univ Clementino Fraga Filho Lab de AIDS
                          / Av BrigadeiroTrompowski s/n / 4o andar Ilha
                          do FuRio de Janeiro RJ, Dr Mauro Schechter
                          (212)703-114 Recruiting 010119.

47
UNIQUE IDENTIFIER         NIH/01355
PROTOCOL ID NUMBERS       NIAID ACTG A5079
PROTOCOL TITLE            A Prospective, Multicenter, Randomized,
                          Placebo-Controlled Trial of Physiologic
                          Testosterone Supplementation for HIV-Positive
                          Men with Mildly to Moderately Reduced Serum
                          Testosterone Levels and Abdominal Obesity.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To test the hypothesis that the
                          change in visceral fat cross-sectional area
                          from baseline to 24 weeks will be greater
                          with testosterone replacement than with
                          placebo in HIV-positive men with abdominal
                          obesity who have mildly to moderately reduced
                          serum testosterone levels.
GENERAL DESCRIPTION       RATIONALE: Reports suggest that many
                          HIV-infected patients on antiretroviral
                          therapy experience an increase in abdominal
                          fat. The mechanisms of abdominal fat
                          accumulation in HIV-infected patients are not
                          known. Studies have shown: treatment with
                          testosterone gel reduces total body fat in
                          young, androgen-deficient men; testosterone
                          replacement in middle-aged men with
                          mid-segment obesity decreases visceral fat;
                          and replacement doses of testosterone
                          decrease fat mass and augment lean body mass
                          in HIV-infected men with androgen deficiency.
                          Therefore, there is a strong rationale for
                          evaluating the effectiveness of testosterone
                          replacement in HIV-infected men with visceral
                          obesity and low testosterone levels.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified based on
                          their viral load. Patients receive either
                          testosterone gel or placebo applied to the
                          skin once daily for 24 weeks. Patients remain
                          on stable potent antiretroviral regimens,
                          which are not supplied through the study.
                          Patients who receive testosterone during the
                          first 24 weeks are eligible to receive it for
                          an additional 24 weeks. Patients on placebo
                          are followed for an additional 24 weeks.
                          Clinical and laboratory evaluations for
                          visceral fat changes are performed throughout
                          the study.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 86 patients. 43 per arm.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/86.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 15
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001219)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG 5079
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2.
                          Waist-to-hip ratio greater than 0.95 or
                          abdominal circumference greater than 100 cm.
                          3. Self-report of increasing abdominal girth,
                          and increasing belt or waist size after
                          initiation of antiretroviral therapy. 4.
                          Plasma HIV-1 RNA copy number equal to or less
                          than 10,000 copies/ml documented within 6
                          weeks prior to screening.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.1 g/dl Or equal to or less
                          than the upper limit of normal (ULN) for the
                          laboratory.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN ULN (Upper Limit of
                          Normal). If total bilirubin is > 1.5 ULN,
                          fractionate to obtain direct and indirect
                          bilirubin. Patients receiving indinavir are
                          eligible if their total bilirubin is < 4 x
                          ULN and th
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Serum total testosterone 125-400
                          ng/dl. Prostate-specific antigen < 4 ng/ml.
                          Serum thyroid-stimulating hormone (TSH) level
                          in the normal range for the local laboratory.
                          Body mass index (BMI) => 18 kg/m2 or =< 40
                          kg/m2. Fasting serum glucose =< 126 mg/dl.
                          Plasma triglyceride level =< 1000 mg/dl.
                          Patients who are not fasting and have
                          triglycerides > 1000 mg/dl should return to
                          the clinic in a fasting state for this
                          measurement.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable potent
                          antiretroviral therapy regimens for at least
                          12 weeks prior to study entry.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Potent
                          antiretroviral therapy for at least 24 weeks
                          after entering study. Allowed: 1. Granulocyte
                          colony-stimulating factor (G-CSF). 2.
                          Standard maintenance and prophylaxis therapy
                          for opportunistic infections provided
                          patients have been on a stable dosage regimen
                          for 2 weeks prior to screening. 3.
                          Erythropoietin. 4. Symptomatic therapy
                          (analgesics, antihistamines, antiemetics,
                          antidiarrheal agents, etc.). 5. Replacement
                          levels of thyroid drugs (same drug and dose
                          at 30 days prior to entry). 6. Initiation or
                          change in lipid-lowering therapy at the
                          discretion of the investigator in
                          consultation with the protocol chairs, during
                          the open-label phase of the study.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 70 years.
PATIENT SEX               MALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of prostate cancer. 2. Grade 2
                          diarrhea defined as 5-7 loose stools per day
                          or diarrhea lasting longer than 1 week,
                          within 6 weeks of study entry. 3. History of
                          unstable angina or decompensated heart
                          failure. 4. History of thromboemboli. 5.
                          History of sleep apnea.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence that, in the
                          opinion of the investigator, would interfere
                          with adherence to study requirements.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: 1. Initiation of a
                          weight reduction or lipid-lowering diet for
                          at least 12 weeks prior to study entry. 2.
                          Initiation of any new resistance training
                          exercise or heavy endurance type of exercise
                          for at least 12 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Visceral
                          radiation.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any
                          testosterone derivative, glucocorticoids, any
                          appetite stimulant, dronabinol, megestrol
                          acetate, androstenediols, oxandrolone, or any
                          other anabolic agents such as
                          dehydroepiandrosterone (DHEA) or growth
                          hormone within 12 weeks prior to study entry.
                          2. Hydroxyurea within 30 days of study entry.
                          3. Change in lipid-lowering therapy for 24
                          weeks prior to study, if patient is on
                          lipid-lowering therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          chemotherapy. 2. Antidiabetic medications,
                          including but not limited to insulin,
                          acetohexamide, chlorpropramide, glimepiride,
                          glipizide, glyburide, tolazamide, acarbose,
                          metformin, rosiglitazone, and pioglitazone.
                          3. Granulocyte-macrophage colony-stimulating
                          factor (GM-CSF). 4. Cytokines (e.g.,
                          interleukins and interferon) or cytokine
                          inhibitors (e.g., thalidomide). 5.
                          Ketoconazole. 6. Concomitant use of ritonavir
                          with simvastatin or lovastatin. 7.
                          Experimental therapies (not FDA approved) or
                          medications in other blinded studies. 8.
                          Initiation of any new therapy that is
                          designed to promote weight gain or loss,
                          including both prescription (e.g., dronabinol
                          and megestrol acetate) and nonprescription
                          products. 9. Prescribed structured treatment
                          interruptions in antiretroviral therapy. 10.
                          Anabolic hormones (e.g., growth hormone and
                          testosterone [in addition to study drug]) and
                          other anabolic steroids. 11. Systemic
                          glucocorticoids. 12. Hydroxyur
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Any active
                          malignancy, except stable, limited cutaneous
                          lesions that are not anticipated to require
                          systemic chemotherapy or visceral radiation
                          while on study. 2. Prostatic enlargement
                          associated with an American Urological
                          Association (AUA) symptom score greater than
                          7. 3. Unresolved prostate abnormality
                          detected on digital rectal examination. 4.
                          Diabetes mellitus defined as fasting serum
                          glucose greater than 126 mg/dl. Patients with
                          random glucose levels greater than 126 mg/dl
                          should have blood drawn for serum glucose
                          evaluations after fasting for at least 8
                          hours. Patients with diabetes mellitus
                          (treated or untreated) will be excluded. 5.
                          Systolic blood pressure greater than 160 mm
                          Hg. Diastolic blood pressure greater than 100
                          mm Hg. 6. Any active opportunistic infection
                          (OI). Patients who are on stable OI
                          maintenance therapy for at least 12 weeks
                          will be allowed. 7. Undiagnosed palpable
                          breast mass. 8. Allergy to components of
                          testosterone gel.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0339  Testosterone
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 10 g applied once
                          daily
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Topical gel
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks with an optional
                          additional 24 weeks.
OTHER TREATMENT INFO.     END POINT: Change in visceral fat
                          cross-sectional area from baseline to Week
                          24, measured by CT scan.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Grade 4 study
                          drug-related toxicity. Patients who develop a
                          Grade 3 study drug-related toxicity may be
                          continued on study drug at the discretion of
                          the investigator. The protocol team should be
                          notified about these toxicities and the
                          investigator's intent to continue or
                          discontinue the study drug. 2. Refusal by
                          patient or legal guardian of further
                          treatment and/or follow-up evaluations. 3.
                          Determination by the investigator that
                          further participation would be detrimental to
                          the patient's health or well-being. 4.
                          Patient failure to comply with the study
                          requirements so as to cause harm to self or
                          seriously interfere with the validity of the
                          study results. 5. Patient requirement for
                          treatment with disallowed medications. 6.
                          Non-compliance defined as patient missing
                          more than 2 consecutive weeks of study
                          treatment. 7. Generalized debilitation or
                          transfer to nursing home or hospice such that
                          follow-up visits and administration of study
                          medication are no longer possible. 8.
                          Detection of prostate or breast cancer at any
                          time during treatment.
OTHER TREATMENT INFO.     MODIFICATION: No dosage reduction of the
                          study drugs will be allowed.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010625.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010625.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 010625.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 010702.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 010625.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010731.
HAWAII                    Queens Med Ctr Leahi Hospital / Young
                          Building / 3675 Kilauea Ave Honolulu, HI
                          96816 Debra Ogata-Arakaki [phone]
                          Recruiting 010625.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010625.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010625.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010625.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010625.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010625.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010625.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 010625.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010625.

48
UNIQUE IDENTIFIER         FDA/01354
PROTOCOL ID NUMBERS       FDA 316B
PROTOCOL TITLE            A Randomized, Open-Label, Two Arm Trial to
                          Compare the Safety and Antiviral Efficacy of
                          GW433908/Ritonavir QD to Nelfinavir BID When
                          Used in Combination with Abacavir and
                          Lamivudine for 48 Weeks in Antiretroviral
                          Therapy Naive HIV-1 Infected Subjects.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To compare the magnitude and the
                          durability of antiviral response of
                          GW433908/ritonavir (RTV) qd and nelfinavir
                          (NFV) bid when used in combination with
                          abacavir (ABC)/lamivudine (3TC) bid over 48
                          weeks in antiretroviral therapy (ART)-naive
                          patients. Methodology: Patients are
                          randomized to 1 of 2 treatment arms. One arm
                          is treated with GW433908/RTV plus ABC and
                          3TC. The other is treated with NFV plus ABC
                          and 3TC. Each group is treated for 48 weeks.
                          The following are compared in the 2 arms: 1)
                          magnitude and durability of antiviral
                          response; 2) safety, tolerance, and antiviral
                          response after 24 and 48 weeks of therapy; 3)
                          time to treatment failure; 4) immunologic
                          response; 5) occurrence of events related to
                          metabolic abnormalities; and 6) development
                          of viral resistance in a subset of patients
                          following treatment. Also studied are: 1)
                          steady-state plasma drug trough
                          concentrations; 2) demographic, virologic,
                          immunologic, pharmacologic, and adherence
                          factors that may be associated with treatment
                          outcome; 3) patient adherence to the drug
                          regimens; 4) study medication utilization;
                          and 5) resource utilization.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to 1 of
                          2 treatment arms. One arm is treated with
                          GW433908/RTV plus ABC and 3TC. The other is
                          treated with NFV plus ABC and 3TC. Each group
                          is treated for 48 weeks. The following are
                          compared in the 2 arms: 1) magnitude and
                          durability of antiviral response; 2) safety,
                          tolerance, and antiviral response after 24
                          and 48 weeks of therapy; 3) time to treatment
                          failure; 4) immunologic response; 5)
                          occurrence of events related to metabolic
                          abnormalities; and 6) development of viral
                          resistance in a subset of patients following
                          treatment. Also studied are: 1) steady-state
                          plasma drug trough concentrations; 2)
                          demographic, virologic, immunologic,
                          pharmacologic, and adherence factors that may
                          be associated with treatment outcome; 3)
                          patient adherence to the drug regimens; 4)
                          study medication utilization; and 5) resource
                          utilization.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010618)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy, Drug
                          safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 624 patients. 624
                          worldwide; 150 U.S.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks
                          minimum.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 459/624 010618.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 37
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: APV30002
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have the signed consent of a parent or legal
                          guardian if under 18 years of age. 2. Have
                          screening plasma HIV-1 RNA of 1,000 copies/ml
                          or greater (if no other documentation of HIV
                          infection exists, a positive result here will
                          serve as documentation for this study). 3. Be
                          of non-childbearing potential or agree to use
                          a proven barrier method of contraception
                          (e.g., spermicide plus condom) during the
                          study period. Hormonal contraceptives are not
                          considered sufficient.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Not specified.
PATIENT INCLUSION CRIT.   SGOT(AST): < Grade 3 within 28 days of study
                          entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): < Grade 3 within 28 days of study
                          entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Negative pregnancy test.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of clinically relevant pancreatitis
                          or hepatitis within the last 6 months. 2.
                          History of drug or other allergy which, in
                          the opinion of the investigator,
                          contraindicates participation in the trial or
                          known hypersensitivity to any study
                          medications.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current alcohol or illicit
                          drug use which, in the opinion of the
                          investigator, may interfere with the
                          patient's ability to comply with the
                          requirements of the study. Note: patients
                          stable on methadone can be considered for
                          participation.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 28 days of study drug administration.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy (defined as 4 weeks or more with any
                          nucleoside reverse transcriptase inhibitor
                          [NRTI] and no nonnucleoside reverse
                          transcriptase inhibitor [NNRTI] or protease
                          inhibitor [PI]) following documented
                          infection. Mothers who have previously
                          received 1 dose of the NNRTI nevirapine
                          during pregnancy for prevention of
                          mother-to-child HIV transmission are
                          permitted to enter the study. 2. Cytotoxic
                          chemotherapeutic agents within 28 days of
                          study drug administration. 3.
                          Immunomodulating agents (such as systemic
                          corticosteroids, interleukins, or
                          interferons) or any agent with known anti-HIV
                          activity (such as hydroxyurea or foscarnet)
                          within 28 days of study drug administration.
                          4. HIV vaccine within 3 months prior to
                          commencement of study drug. 5. The following
                          medications within 28 days of commencement of
                          study drug: amiodarone, astemizole, bepridil,
                          bupropion, cisapride, clorazepate, clozapine,
                          diazepam, dihydroergotamine, encainide,
                          ergonovin
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapeutic agents. 2. Within 28 days of
                          commencement of study drug: amiodarone,
                          astemizole, bepridil, bupropion, cisapride,
                          clorazepate, clozapine, diazepam,
                          dihydroergotamine, encainide, ergonovine,
                          ergotamine, estazolam, flecainide,
                          flurazepam, lovastatin, meperidine,
                          methylergonovine, midazolam, pimozide,
                          piroxicam, propafenone, propoxyphene,
                          quinidine, rifabutin, simvastatin,
                          terfenadine, triazolam, and zolpidem (these
                          drugs have been excluded for safety reasons);
                          phenobarbital, phenytoin, carbamazepine,
                          dexamethasone, troglitazone, primidone,
                          ethosuximide, rifampin, and St. John's wort
                          (these drugs have been excluded because they
                          have the potential to decrease plasma
                          protease inhibitor concentrations). 3. Other
                          investigational drugs/therapies (note:
                          treatments available through a treatment IND
                          or other expanded-access mechanism will be
                          evaluated on a case-by-case basis in
                          consultation with the sponsor). 4.
                          Antiretroviral drugs (o
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Active/acute CDC
                          Category C event (per 1993 classification).
                          2. Malabsorption syndrome or other
                          gastrointestinal dysfunction which might
                          interfere with drug absorption or render the
                          patient unable to take oral medication. 3.
                          Any serious medical condition (e.g.,
                          diabetes, cardiac dysfunction, hepatitis)
                          which, in the opinion of the investigator,
                          might compromise the safety of the patient.
                          4. Any acute laboratory abnormality at
                          screening which, in the opinion of the
                          investigator, should preclude the patient's
                          participation in the study of an
                          investigational compound. Any Grade 4
                          laboratory abnormality at screening will
                          exclude a patient from study participation.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0337  GW433908
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 3: 1395 mg qd. (Change
                          to 1400mg qd at Week 32)
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 3: 1395 mg. (1400mg)
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral. Drug 5: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
SUPPORTING AGENCY         Glaxo Wellcome Inc.
LAST REVISION DATE        20010618
CALIFORNIA                Kaiser Hospital 2025 Morse Ave Sacramento, CA
                          95825 Jason Flamm [phone] Recruiting
                          010619.
CALIFORNIA                AIDS Research Alliance 621-A North San
                          Vicente Blvd West Hollywood, CA 90069 Stephen
                          Brown [phone] Recruiting 010619.
CALIFORNIA                Park Ctr for Health / Keith Vrhel 4067 Park
                          Blvd San Diego, CA 92103 Keith Vrhel
                          [phone] Recruiting 001219.
CALIFORNIA                Orange County Ctr for Special Immunology
                          11190 Warner Ave Fountain Valley, CA 92708
                          Paul Cimoch [phone] Recruiting 001219.
CALIFORNIA                AIDS Healthcare Foundation 1300 North Vermont
                          Ave / Suite 606 Los Angeles, CA 90027 Charles
                          Farthing [phone] Recruiting 001219.
CALIFORNIA                LAGLC 1625 N Schrader Blvd Rm 319 Los
                          Angeles, CA 90028 Robert Bolan [phone]
                          Recruiting 010619.
DISTRICT OF COLUMBIA      Dupont Circle Physicians Group 1737 20th St
                          NW Washington, DC 200091104 Richard Elion
                          [phone] Recruiting 010619.
FLORIDA                   Infectious Diseases Associates 1425 South
                          Osprey Ave Sarasota, FL 34239 Vilma Vega
                          [phone] Recruiting 001219.
FLORIDA                   CRI of South Florida 1320 South Dixie Hwy
                          Coral Gables, FL 33146 Allan Stein
                          [phone] Recruiting 001219.
FLORIDA                   Univ of Miami Dept of Medicine 1800 Northwest
                          10th Ave / R-60A Miami, FL 33136 Margaret A
                          Fischl [phone] Recruiting 010619.
FLORIDA                   Infectious Disease Research Inst 4620 N
                          Habana Ave Tampa, FL 33614 Bienvenido Yangco
                          [phone] Recruiting 001219.
FLORIDA                   Specialty Med Care Ctrs of South Florida Inc
                          1313 NW 36th St Miami, FL 33142 Ronald
                          Lubetsky [phone] Recruiting 001219.
FLORIDA                   Gary Richmond MD 315 Southeast 14th St Fort
                          Lauderdale, FL 33316 Gary Richmond
                          [phone] Recruiting 001219.
FLORIDA                   Jeffrey Levenson 6798 Crosswinds St
                          Petersburg, FL 33710 Jeffrey Levenson
                          [phone] Recruiting 001219.
FLORIDA                   Infectious Disease Consultants 685 Palm
                          Springs Dr Altamonte Springs, FL 32701 Edwin
                          DeJesus [phone] Recruiting 001219.
FLORIDA                   Therafirst Med Ctr 4011 North Federal Hwy
                          Fort Lauderdale, FL 33308 Anthony LaMarca
                          [phone] Recruiting 001219.
GEORGIA                   SMO USA 1820 Highway 20 Conyers, GA 30013
                          Gerald Pierone [phone] Recruiting
                          001219.
GEORGIA                   Med College of Georgia 1521 Pope Ave / Bldg
                          FF119 Augusta, GA 30912 Cheryl Newman
                          [phone] Recruiting 010619.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon Ave Atlanta, GA 30308 Melanie A
                          Thompson [phone] Recruiting 001219.
INDIANA                   Indiana Univ Med School 1001 West 10th St
                          Indianapolis, IN 46202 Lawrence Wheat
                          [phone] Recruiting 010619.
MASSACHUSETTS             Hawthorne Med Associates / PAACA 4586A
                          Acushnet Ave New Bedford, MA 02745 Andrew
                          Artenstein [phone] Recruiting 001219.
MASSACHUSETTS             Brigham and Women's Hosp 75 Francis St
                          Boston, MA 02115 Paul Sax [phone]
                          Recruiting 010619.
MINNESOTA                 Abbott-Northwestern Hosp / Clinic 42 2545
                          Chicago Ave South Minneapolis, MN 55404 Frank
                          Rhame [phone] Recruiting 010619.
MISSOURI                  Southampton Healthcare Inc 2340 Hampton Ave
                          St Louis, MO 63139 David Parks [phone]
                          Recruiting 001219.
NEW JERSEY                VAMC New Jersey Healthcare System 385 Tremont
                          Ave East Orange, NJ 07018 Robert Eng
                          [phone] Recruiting 010619.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Ronald Poblete [phone]
                          Recruiting 010619.
NEW YORK                  Bronx Veterans Affairs Med Ctr 130 West
                          Kingsbridge Rd Bronx, NY 10468 Sheldon Brown
                          [phone] Recruiting 010619.
NEW YORK                  North Shore Univ Hosp 300 Community Dr
                          Manhasset, NY 11030 David Shepp [phone]
                          Recruiting 010619.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Ross Hewitt
                          [phone] Recruiting 010619.
NEW YORK                  St Lukes - Roosevelt Hosp Ctr 432 West 58th
                          St New York, NY 10019 George McKinley
                          [phone] Recruiting 010619.
OHIO                      Univ of Cincinnati / Holmes Hosp Eden and
                          Albert Sabin Way Cincinnati, OH 452670405
                          Judith Feinberg [phone] Recruiting
                          010619.
PENNSYLVANIA              Hahnemann Univ Hosp Broad and Vine Sts / MS
                          209 Philadelphia, PA 19102 Daniel Alvarez
                          [phone] Recruiting 010619.
PENNSYLVANIA              Milton S Hershey Med Ctr 500 Univ Dr Hershey,
                          PA 170330850 Elaine Eyster [phone]
                          Recruiting 010619.
SOUTH CAROLINA            Burnside Clinic 14 Calendar Ct Columbia, SC
                          29206 Alfred Burnside [phone]
                          Recruiting 001219.
TENNESSEE                 Methodist Healthcare 1265 Union Avenue
                          Memphis, TN 38104 Danny Lancaster
                          [phone] Recruiting 010619.
TEXAS                     Joseph C Gathe 1200 Binz / Suite 120 Houston,
                          TX 77004 Joseph Gathe [phone]
                          Recruiting 001219.
TEXAS                     Nicholas Bellos 3801 Gaston Ave Suite 300
                          Dallas, TX 75246 Lee Ann OIiver [phone]
                          Recruiting 001219.

49
UNIQUE IDENTIFIER         NIH/01353
PROTOCOL ID NUMBERS       NIAID ACTG A5068
PROTOCOL TITLE            A Randomized Phase I/II Pilot Study of
                          Intermittent Withdrawal of Antiretroviral
                          Therapy as an Immunization Strategy and
                          Double-Blinded Immunization with ALVAC-HIV
                          vCP1452 in Subjects with Persistent CD4+ Cell
                          Counts Greater Than 500 Cells/mm3 and Plasma
                          HIV-1 RNA Levels < 50 Copies/ml.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Therapeutic AIDS Vaccine
GENERAL DESCRIPTION       PURPOSE: To compare the effects of different
                          methods of antigen stimulation (intermittent
                          potent antiretroviral therapy [ART]
                          withdrawal versus ALVAC versus both) versus
                          no antigen stimulation on the mean of the
                          log10 HIV-1 RNA copies/ml in the last 2 weeks
                          of the endpoint readout period (Step 6) of
                          potent ART withdrawal. To establish the
                          safety of intermittent withdrawal of ART with
                          and without HIV-specific vaccine in patients
                          with persistent CD4+ T-cell counts greater
                          than 500/mm3 and persistent plasma HIV-1 RNA
                          levels below 50 copies/ml.
GENERAL DESCRIPTION       RATIONALE: The best hope for long-term
                          control of HIV infection in an individual
                          probably rests with the resumption of
                          effective HIV-specific immune responses.
                          A5068 hopes to determine whether intermittent
                          antiretroviral therapy withdrawal serves to
                          stimulate HIV-specific immune responses and
                          control of viral replication. This approach
                          will be compared with vaccination with
                          ALVAC-HIV vCP1452. In addition, it is
                          conceivable that intermittent antiretroviral
                          therapy withdrawal could boost and broaden
                          the prime response to exogenous vaccine and
                          that will be studied as well.
GENERAL DESCRIPTION       METHODOLOGY: Patients continue receiving
                          their potent ART (not provided by the study)
                          and are randomized to 1 of 4 treatment
                          strategies as follows: Arm A: ALVAC placebo
                          and potent ART for 92 weeks with a single 12-
                          to 20-week therapy withdrawal period. Arm B:
                          ALVAC placebo and potent ART for 84 weeks
                          with a 4- to 6-week therapy withdrawal
                          period, a 4-week therapy withdrawal period,
                          and a 12- to 20-week therapy withdrawal
                          period. Arm C: ALVAC vCP1452 vaccine and
                          potent ART for 92 weeks with a single 12- to
                          20-week therapy withdrawal period. Arm D:
                          ALVAC vCP1452 vaccine and potent ART for 84
                          weeks with a 4- to 6-week therapy withdrawal
                          period, a 4-week therapy withdrawal period,
                          and a 12- to 20-week therapy withdrawal
                          period. Immunizations of placebo or vaccine
                          are administered in 3 separate sets of 3
                          injections per set (9 total). The study is a
                          multiple-step study. Patients in Arms B and D
                          receive a 4-week period of potent ART therapy
                          along with the first set of immunizations
                          (Step 1) followed by therapy withdrawal for
                          4-6 weeks (Step 2). Alternating periods of
                          therapy resumption (Step 3, consisting of 16
                          weeks on potent ART with the second set of
                          vaccine administrations), a second therapy
                          withdrawal (Step 4 for 4 weeks), and another
                          therapy resumption (Step 5, consisting of 16
                          weeks on potent ART with the third set of
                          vaccine administrations) follow. Patients in
                          Arms A and C remain on Step 1 for the first
                          44 weeks on study. After 44-46 weeks on
                          study, patients in all arms have therapy
                          withdrawn for 12-20 weeks (Step 6). Following
                          completion of Step 6, patients whose HIV-1
                          RNA levels are below 10,000 copies/ml are
                          encouraged to remain off potent ART (Step 7)
                          until completion of the study as long as CD4+
                          T-cell levels remain 50 percent or more of
                          their baseline levels. Otherwise, patients
                          restart their potent ART regimens (Step 8)
                          and receive virologic and CD4+ T-cell
                          monitoring until completion of the study. All
                          patients are monitored at regular clinic
                          visits. HIV-1 RNA levels and CD4+ T-cell
                          counts are measured. Male patients may
                          participate in substudy A5101s (Male Genital
                          Secretions) and patients in Arms B and D may
                          participate in substudy A5111s (Latent
                          Infected T-Cell Clearance).
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Immunology, Strategy determination.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients. 25 in each
                          of 4 treatment arms.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: About 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 9/100 010731.
PROTOCOL DETAILS          STUDY DURATION: About 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 12
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001128)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5068. Substudy
                          AACTG A5101s. Substudy AACTG A5111s
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection documented by any
                          licensed ELISA test kit and confirmed by
                          Western blot, HIV-1 culture, HIV-1 antigen,
                          plasma HIV-1 RNA, or a second antibody test
                          by a method other than ELISA at any time
                          before study entry. 2. Have documentation of
                          current, persistent CD+ T-cell counts greater
                          than 500 cells/mm3 for a period of at least 6
                          months before study entry, in which 1 month
                          equals 30 days, verified by at least 3
                          measurements separated from each other by at
                          least 1 month, with the first measurement
                          performed at least 6 months before study
                          entry and the other 2 measurements performed
                          within 6 months of study entry. All CD4+
                          T-cell counts obtained within 6 months prior
                          to study entry must be greater than 500
                          cells/mm3. 3. Have documentation of current,
                          persistent HIV-1 RNA levels below 400
                          copies/ml for a period of at least 6 months
                          before study entry, in which 1 month equals
                          30 days, verified by at least 3 measurements
                          separated from each other by at least 1
                          month, with the first measurement performed
                          at least 6 months before study entry and the
                          other 2 measurements performed within 6
                          months of study entry. All HIV-1 RNA levels
                          obtained within 6 months prior to study entry
                          must be less than 400 copies/ml. Have an
                          HIV-1 RNA level below 50 copies/ml by the
                          Roche Amplicor HIV-1 Monitor UltraSensitive
                          assay at study screening. 4. Have a negative
                          urine or serum beta-HCG pregnancy test within
                          45 days before study entry. 5. Provide
                          documentation of menopause, sterilization, or
                          azoospermia, if female not of reproductive
                          potential (have reached menopause or
                          undergone hysterectomy, oophorectomy, or
                          tubal ligation). 6. Agree not to participate
                          in a conception process (e.g., active attempt
                          to become pregnant or to impregnate, sperm
                          donation, in vitro fertilization), and if
                          participating in sexual activity that could
                          lead to pregnancy, the female study
                          patient/male partner must use a reliable form
                          of contraception while receiving
                          protocol-specified medication and for 12
                          weeks after study completion. 7. Have consent
                          of parent or guardian if under 18 years of
                          age.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.1 g/dl for men and > 8.9 g/dl
                          for women, within 45 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3 Within 45 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 500 cells/mm3 For at
                          least 6 months before study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN ULN (Upper Limit of
                          Normal). Unless elevated due to patient
                          receiving indinavir and in the absence of
                          other evidence of significant liver disease.
                          Within 45 days prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 45 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 45 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN Within 45 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception during the study and for 90
                          days after Not breast-feeding Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Acupuncture.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Currently
                          receiving first potent ART regimen. Patients
                          who have received a potent ART regimen that
                          was changed to the current potent ART
                          regimen, for reasons other than virologic
                          failure (potent ART is defined as a
                          3-or-more-drug combination antiretroviral
                          therapy regimen), may be eligible. Allowed:
                          1. Topical corticosteroids. If a patient
                          requires frequent topical therapy to a large
                          surface area of the body, the protocol
                          co-chairs should be contacted to discuss
                          whether the patient should continue to
                          participate in this study. 2. Systemic
                          corticosteroids for short periods (less than
                          21 days) for acute conditions, though the
                          protocol co-chairs should be notified. 3.
                          Anabolic steroids. 4. Maintenance therapy for
                          opportunistic infections that develop while
                          on study according to standards of medical
                          care, except rifabutin and rifampin at any
                          time. 5. Antibiotics for bacterial
                          infections. 6. Regularly prescribed
                          medications, such as antipyretics,
                          analgesics, antidepressants, antihistamines,
                          sleep medications, oral contraceptives,
                          megestrol acetate, testosterone, and other
                          medications for chronic conditions that do
                          not affect the immune system. 7. Alternative
                          therapies, such as vitamins. 8.
                          Erythropoietin and filgrastim (G-CSF), when
                          clinically indicated. 9. Licensed, non-HIV,
                          killed or subunit vaccines may be
                          administered provided they are given more
                          than 1 month before and 1 month after the HIV
                          vaccine being administered in this protocol,
                          and at least 14 days prior to any HIV-1 RNA
                          measurement and at least 30 days prior to an
                          HIV-1 RNA measurement that will be used to
                          determine eligibility for any step in the
                          protocol. Licensed, non-HIV, killed, or
                          subunit vaccines may not be administered
                          during any period of treatment interruption.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Any acute infection or medical illness within
                          14 days before study entry. 2. History of
                          lymph node irradiation. 3. Close contact
                          through working with canaries (e.g., breeding
                          farms, bird shops) likely to induce
                          development of antibodies to canarypox before
                          study enrollment (individuals with a pet
                          canary are not excluded). 4. HIV-1
                          seroconversion within 1 year before study
                          entry.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence which, in the
                          opinion of the investigator, would interfere
                          with adherence to study requirements.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Lymph node
                          irradiation.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any immune
                          modulators or suppressors within 45 days of
                          study entry including but not limited to
                          drugs such as systemic corticosteroids;
                          interferons; interleukins; thalidomide;
                          sargramostim (granulocyte-macrophage
                          colony-stimulating factor [GM-CSF]);
                          dinitrochlorobenzene (DNCB); thymosin alpha;
                          thymopentin; inosiplex; polyribonucleoside;
                          and ditiocarb sodium. 2. Hydroxyurea within
                          45 days before study entry. 3. Any HIV
                          vaccine. 4. Any interruption in potent ART of
                          greater than 7 consecutive days within 1 year
                          before study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Abacavir as
                          part of the current potent ART regimen;
                          interferons; interleukins; sargramostim
                          (GM-CSF); dinitrochlorobenzene (DNCB);
                          thymosin alpha 1; thymopentin; rifampin;
                          rifabutin; inosiplex; polyribonucleoside;
                          ditiocarb sodium; investigational
                          antiretroviral agents; thalidomide; systemic
                          or local cytotoxic chemotherapy for
                          malignancy; immunoenhancing or
                          immunosuppressive drugs such as cyclosporin,
                          methotrexate, azathioprine, anti-CD25
                          antibody; systemic corticosteroids for long
                          periods (21 days or more); any HIV-specific
                          vaccine other than the one specified in this
                          protocol; hydroxyurea; systemic cytotoxic
                          chemotherapy; and medications whose use is
                          contraindicated in the presence of the
                          patient's antiretroviral therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Any malignancy
                          that may require systemic therapy. 2.
                          Sensitivity or allergy to albumin.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm C: 1.0 ml at
                          weeks 0, 1, 2, 20, 21, 22, 40, 41, andArm D:
                          1.0 ml at weeks 0, 1, and 2
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular
OTHER TREATMENT INFO.     END POINT: The readout period of potent ART
                          withdrawal is defined as the third potent
                          ART withdrawal period in Arms B and D and the
                          first potent ART withdrawal period in ARMS A
                          and C, and, regardless of how long a patient
                          remains off ART therapy, the readout period
                          ends either when the patient resumes ART
                          therapy or 20 weeks after commencement of the
                          readout period, whichever comes first. 1.
                          Mean of log10 HIV-1 RNA copies/ml at the last
                          2 scheduled evaluations during the endpoint
                          readout period of potent ART withdrawal
                          (final viral setpoint). 2. For arms with
                          intermittent potent ART withdrawal (Arms B
                          and D), a dichotomous safety endpoint is
                          defined as negative if, after at least a
                          16-week retreatment period before the
                          endpoint readout therapy withdrawal period:
                          (1) the patient fails to achieve less than
                          1,000 HIV-1 RNA copies/ml or (2) the patient
                          fails to achieve a CD4+ T-cell count or
                          percentage of 70 percent or higher of their
                          baseline CD4+ T-cell count or percentage;
                          otherwise, positive. For arms without an
                          intermittent potent ART withdrawal (Arms A
                          and C), a dichotomous safety endpoint is
                          defined as negative if, after 44 weeks in
                          Step 1: (1) the patient fails to achieve
                          under 1,000 HIV-1 RNA copies/ml or (2) the
                          patient fails to achieve a CD4+ T-cell count
                          or percentage of 70 percent or higher of
                          their baseline CD4+ T-cell count or
                          percentage; otherwise, positive.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Study completion.
                          2. Refusal of further treatment and/or
                          follow-up evaluations by the patient or legal
                          guardian. 3. Pregnancy. 4. Determination that
                          further participation would be detrimental to
                          the patient's health or well-being. 5.
                          Failure to adhere to study regimen or other
                          study requirements so as to cause harm to
                          self or seriously interfere with the validity
                          of the study results. 6. Treatment required
                          with medications that are disallowed while on
                          this study. 7. A change in therapy regimen
                          not approved by the study co-chairs. 8.
                          Detection of mutations in viral isolates with
                          the potential to confer resistance to current
                          antiretroviral therapy.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 010423.
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010318.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010423.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010502.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Dilcia Ortega
                          [phone] Recruiting 010423.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 010318.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010418.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 010406.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 010423.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] Recruiting 010522.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Chip
                          Lohner [phone] Recruiting 010627.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010605.

50
UNIQUE IDENTIFIER         FDA/01351
PROTOCOL ID NUMBERS       FDA 315A
PROTOCOL TITLE            A Randomized Open-Label Trial Comparing the
                          Tolerability of Videx EC Capsules to Videx
                          Tablets in Adults with HIV Infection.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare between treatment arms
                          the proportion of patients, at Study Week 2,
                          with a Gastrointestinal Symptom Rating Scale
                          (GSRS) rating of at least 2.0 (frequent or
                          prolonged and troublesome) on at least 1 of
                          the following items: abdominal pains, nausea
                          and vomiting, borborygmus, abdominal
                          distension, and loose stools.
GENERAL DESCRIPTION       RATIONALE: Despite its therapeutic advantages
                          and proven efficacy in the treatment of
                          HIV-infected patients, didanosine may
                          continue to be underutilized because many
                          patients experience undesirable
                          gastrointestinal (GI) side effects and
                          palatability problems. Once-daily dosing with
                          Videx EC is expected to improve patient
                          adherence with possible improved palatability
                          and remove the GI side effects associated
                          with the buffers included in the tablet.
                          Videx EC once-daily dosing would improve pill
                          burden by decreasing from 2 tablets to 1
                          capsule per day. Therefore, Videx EC may
                          represent a significant step toward achieving
                          better patient satisfaction, improved regimen
                          adherence, and optimal virologic outcomes
                          with Videx-containing regimens.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          either continue their current Videx
                          tablet-containing regimen for an additional 2
                          weeks or replace their Videx tablets with
                          Videx EC. Patients who remain on Videx
                          tablets are switched to the EC formulation at
                          Study Week 2 for the remaining 4 weeks of the
                          study period. For patients who continue and
                          successfully complete the Week 6 study visit,
                          an optional extended dosing period is offered
                          until Videx EC becomes commercially available
                          or the study funder terminates the study.
                          Blood specimens for safety evaluations and
                          viral load are collected at Weeks 0, 1, 2, 4,
                          and 6. For patients participating in the
                          extended dosing period, the visit schedule is
                          every 8 weeks. Symptom scores between the 2
                          treatment groups are compared, with the
                          primary comparison occurring at the Week 2
                          visit. Analyses include changes in GSRS
                          scores administered by clinician interview at
                          each study visit. Assessment of GI symptoms,
                          palatability features, dosing convenience,
                          lifestyle effects, and Videx preference is
                          evaluated by the patient. Adverse events are
                          assessed objectively by the observations of
                          both the investigator and the patient.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (001208)
PROTOCOL DETAILS          STUDY INTENT: Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 200 patients. 100 per arm.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 8 weeks with
                          optional extended dosing period.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/200.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 15
PROTOCOL DETAILS          VERSION NUMBER & DATE: (000727)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: BMS-006
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patient must: 1.
                          Have documented HIV infection as determined
                          by 1 of the following: (1) positive ELISA
                          confirmed by either Western blot or
                          Immunofluorescence; (2) positive HIV culture;
                          (3) positive HIV p24 antigen detection; or
                          (4) positive plasma HIV RNA detection. 2.
                          Have written informed consent of a legally
                          acceptable representative if patient is not
                          of legal age. 3. Score 2 or higher for 1 or
                          more of the following symptoms: abdominal
                          pain, nausea and vomiting, borborygmus,
                          abdominal distension, and loose stools at
                          Week -2 (Visit 1) and Week 0 (Visit 2) GSRS
                          questionnaires. 4. Have a negative urine
                          pregnancy test at Week -2 (Visit 1) and Week
                          0 (Visit 2), for women of childbearing
                          potential. 5. Be available for a period of at
                          least 8 weeks.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 x ULN Within 30 days of
                          screening.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 1.5 x ULN Within 30 days of
                          screening.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 1.5 x ULN Within 30 days of
                          screening.
PATIENT INCLUSION CRIT.   OTHER: Total serum amylase or lipase <= 1.4 x
                          ULN within 30 days of screening.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Negative pregnancy test within 14 days
                          of study entry Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable
                          Videx-containing antiretroviral regimen,
                          using Videx tablets either once or twice
                          daily, for at least 2 weeks prior to the
                          screening visit.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Trimethoprim/sulfamethoxazole, dapsone,
                          aerosolized pentamidine. Prophylaxis for
                          Pneumocystis carinii pneumonia (PCP) is
                          strongly recommended for patients with CD4
                          cell counts of at least 200/mm3 or prior
                          episodes of PCP. If patients require therapy
                          for PCP with IV pentamidine, Videx should be
                          stopped while IV pentamidine is being
                          administered and for 1 week after cessation
                          of IV pentamidine. Absorption of ketoconazole
                          or other medication requiring the presence of
                          low gastric pH may be inhibited if given at
                          the same time as Videx tablets; oral
                          acidifying agents are not allowed. Patients
                          taking these agents should do so at least 2
                          hours before taking Videx. The choice of drug
                          for Pneumocystis prophylaxis, in accordance
                          with the current CDC guideline, is at the
                          discretion of the investigator. 2.
                          Immunizations recommended by the Advisory
                          Committee on Immunization Practices (ACIP)
                          for routine practice. 3. Erythropoietin,
                          G-CSF, or GM-CSF for myelosuppression
                          emerging on study. 4. Acyclovir or
                          valacyclovir. 5. Standard treatment for
                          tuberculosis management, unless otherwise
                          excluded. 6. All other medically indicated
                          treatments.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 16
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic pancreatitis. 2.
                          History of gallstones.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Excessive alcohol
                          intake which, in the judgment of the
                          investigator, increases the risk of
                          pancreatitis.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Treatment for an
                          active AIDS-defining opportunistic infection
                          within 4 weeks of screening visit. Those
                          patients with chronic candidiasis or
                          bacterial infection will be allowed.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Currently
                          taking Videx oral solution. 2. Medications
                          which, in the judgment of the investigator,
                          increase the risk of pancreatitis. 3.
                          Anticipated or expected change to the
                          patient's currently prescribed HIV
                          medications or complementary or alternative
                          medicines (CAMS) within 8 weeks following the
                          screening visit. 4. Investigational drugs or
                          participation in a clinical trial involving
                          antiretroviral medications; exceptions may be
                          granted for Phase IV studies with approval of
                          PharmaResearch project manager (or designee)
                          on a case-by-case basis. 5. Nelfinavir or
                          amprenavir. 6. Potent neurotoxic drugs
                          including vincristine, zalcitabine, and
                          thalidomide. 7. Drugs that increase serum
                          levels of Videx. For more information, refer
                          to the package insert. 8. Current or
                          anticipated systemic therapy for treatment of
                          malignancy. 9. Oral acidifying agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Current bilateral
                          peripheral neuropathy of at least Grade 2,
                          which, in the opinion of the investigator,
                          precludes study participation. 2. Active
                          ongoing GI disease or infection (e.g.,
                          colitis, diverticulitis, Crohn's disease,
                          peptic ulcer disease, giardiasis,
                          cryptosporidiosis, etc.). 3. Intractable
                          diarrhea or severe malabsorption. 4.
                          Inability to tolerate oral medication. 5. Any
                          other clinical condition or prior therapy
                          that, in the opinion of the investigator,
                          would make the patient unsuitable for the
                          study or unable to comply with the dosing
                          requirements or study scheduled visits.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0016  Didanosine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Videx tablets: Same
                          dose level that patient was taking to study
                          entry. Videx EC: Same dose level that patient
                          was taking for Videx tabprior to study entry
                          or once daily (400 mg qd if at least 60 kg250
                          mg qd if under 60 kg)
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 weeks with optional
                          extended dosing period.
OTHER TREATMENT INFO.     END POINT: Safety (proportion of patients
                          with a GSRS rating of at least 2.0 for any of
                          the following items: abdominal pains, nausea
                          and vomiting, borborygmus, abdominal
                          distension, loose stools).
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Physician's
                          decision including, but not limited to, major
                          toxicity, adverse events, noncompliance, and
                          any other serious and unexpected or
                          life-threatening toxicity. 2. Pregnancy.
                          Patients are followed until the conclusion of
                          the pregnancy. 3. Patient requires disallowed
                          medications. 4. Patient requires a permanent
                          change in his/her current antiretroviral
                          regimen (documented at Week -2 screening
                          visit) at any time during the 8-week study
                          period. 5. Patient's request. Patients who
                          discontinue due to an adverse event should be
                          followed until resolution or 30 days after
                          completing the study.
SUPPORTING AGENCY         PharmaResearch Corp.
LAST REVISION DATE        20001208
CALIFORNIA                Tower ID Med Associates 8631 W 3rd St /
                          #1015E Los Angeles, CA 90048 Shangri La Cully
                          [phone] Recruiting 010105.
CALIFORNIA                Pacific Horizons Med Group 2351 Clay St San
                          Francisco, CA 94115 Amy Sullivan
                          [phone] Recruiting 010104.
CALIFORNIA                Altamed Medical Health Services 5427 East
                          Whittier Blvd Los Angeles, CA 90022 Monica
                          Lopez [phone] Recruiting 010104.
DISTRICT OF COLUMBIA      George Washington Univ Med Ctr 2150
                          Pennsylvania Ave NW Washington, DC 20037
                          Scott Watson [phone] Recruiting 010105.
FLORIDA                   Community Research Initiative of South
                          Florida 1320 South Dixie Hwy Coral Gables, FL
                          33146 Jean Telusma [phone] Recruiting
                          010105.
GEORGIA                   Atlanta VA Med Ctr 1670 Clairmont Rd Mailstop
                          RIM-111 Decatur, GA 30033 Laura Gallager
                          [phone] Recruiting 010105.
MICHIGAN                  Wayne State Univ - WSU/DMC / Univ Hlth Ctr
                          4201 Saint Antoine / POD 7C Detroit, MI 48201
                          Jan Kosmyna [phone] Recruiting 010104.
MINNESOTA                 Park Nicollet Med Ctr / Hlth Education 3800
                          Park Nicollet Blvd / 6th Floor St Louis Park,
                          MN 55416 Renee St Jacque [phone]
                          Recruiting 010104.
NORTH CAROLINA            Jemsek Clinic 16630 Northcross Dr / Suite 102
                          Huntersville, NC 28078 Paula Hutcherson
                          [phone] Recruiting 010104.
NEW YORK                  Treatment for Life Ctr One Brookdale Plaza
                          Brooklyn, NY 112123198 Victor Bouzi
                          [phone] Recruiting 010104.
PENNSYLVANIA              Bornemann Internal Medicine 145 N 6th Street
                          / Suite 205 Reading , PA 19601 Paula Shivers
                          [phone] Recruiting 010105.
SOUTH CAROLINA            Burnside Clinic 14 Calendar Ct Columbia, SC
                          29206 Dan Woodward [phone] Recruiting
                          010104.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 010105.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd / KI - 900 Dallas, TX
                          75235 Claudia Quittner [phone]
                          Recruiting 010105.
VIRGINIA                  Hampton Roads Med Specialists 2112 Executive
                          Dr Hampton, VA 23666 Lois H Ullman
                          [phone] Recruiting 010104.

51
UNIQUE IDENTIFIER         FDA/01349
PROTOCOL ID NUMBERS       FDA 314A
PROTOCOL TITLE            A Phase II, Open Label, Multicenter Study to
                          Assess the Safety and Efficacy of 100 Mg DPC
                          083 Once Daily in Combination with Nucleoside
                          Analogue Reverse Transcriptase Inhibitors in
                          HIV-1-Infected Subjects Who Are Failing
                          Treatment with a Non-Nucleoside Reverse
                          Transcriptase Inhibitor-Containing Regimen.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and
                          tolerability of 100 mg DPC 083 once daily in
                          combination with 2 nucleoside reverse
                          transcriptase inhibitors (NRTIs) in
                          HIV-1-infected patients who are failing
                          therapy with a nonnucleoside reverse
                          transcriptase inhibitor (NNRTI)-containing
                          regimen. To evaluate the efficacy of 100 mg
                          DPC 083 once daily in combination with 2
                          NRTIs in HIV-1-infected patients who are
                          failing therapy with an NNRTI-containing
                          regimen, as assessed by suppression of plasma
                          HIV-1-RNA levels after 8, 24, and 48 weeks of
                          treatment.
GENERAL DESCRIPTION       RATIONALE: Preclinical and human
                          pharmacokinetic data suggest that DPC 083 can
                          be administered once daily and provide trough
                          plasma concentrations of free drug that will
                          suppress replication of HIV-1, including
                          strains containing key resistance mutations
                          observed after failure of treatment with
                          currently available NNRTIs. This study will
                          provide an assessment of safety and a
                          preliminary assessment of the efficacy of DPC
                          083 when administered at a dose of 100 mg
                          once daily in combination with 2 NRTIs, in a
                          population of HIV-1-infected patients who are
                          failing treatment with an NNRTI-containing
                          regimen.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive DPC 083 once
                          daily in combination with 2 NRTIs. The 2
                          NRTIs are selected by the investigators,
                          based on HIV-1 genotyping results. Analyses
                          for patient safety and drug efficacy are done
                          at Weeks 8, 24, and 48 using results from
                          clinical laboratory tests and physical exams.
                          Patients continue to receive DPC 083 and
                          NRTIs until the last patient enrolled in the
                          study completes 48 weeks of treatment.
                          Patients return for post-therapy follow-up
                          visits at 1 and 3 months following early
                          termination or study completion. Some
                          patients may participate in a substudy which
                          evaluates changes in HIV-1 levels in
                          cerebrospinal fluid (CSF).
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010713)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients. A minimum of
                          30 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Screening,
                          treatment until the last patient enrolled has
                          completed 48 weeks treatment, and 3 months
                          post-treatment follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 12/30 010713.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (000929)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: DPC 083-203
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Be 18 years or older (or of legal age of
                          consent, whichever is greater). 2. Have a
                          documented diagnosis of HIV-1 infection by
                          antibody assay (enzyme immunoassay confirmed
                          by Western immunoblot), positive HIV-1
                          culture, or detectable plasma HIV-1-RNA level
                          by reverse transcriptase polymerase chain
                          reaction (RT-PCR). 3. Have documented
                          evidence of virologic failure (not
                          attributable to medication intolerance or
                          nonadherence) after treatment with an NNRTI
                          (nevirapine, delavirdine, or efavirenz) and
                          no more than 2 NRTIs. Virologic failure is
                          defined as follows: failure to achieve a
                          plasma HIV-1-RNA level less than 400
                          copies/ml by RT-PCR assay (or less than 500
                          copies/ml by branched-chain DNA [bDNA] assay)
                          after 6 months of treatment; or documented
                          rebound in plasma HIV-1-RNA level above 400
                          copies/ml by RT-PCR assay (or 500 copies/ml
                          by bDNA assay), confirmed on more than 1
                          occasion, after achieving a plasma HIV-1-RNA
                          level below either of these values. 4. Have
                          screening HIV-1 genotype performed while
                          receiving the NNRTI-containing regimen, or
                          within 2 weeks after stopping that regimen.
                          5. Have plasma HIV-1-RNA levels quantitated
                          by RT-PCR of 1,000 copies/ml or higher within
                          45 days prior to Day 1. 6. Be willing to use
                          an effective, medically-accepted (including
                          barrier) method of contraception during the
                          study, as defined by the principal
                          investigator. Oral or subcutaneous
                          contraceptives should not be used as the only
                          method of birth control. If study medication
                          is discontinued, patients should continue to
                          use contraception for the subsequent 3
                          months.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 10.0 g/dl for males, > 9.0 g/dl
                          for females.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 mg/dl (180 micromol/L).
PATIENT INCLUSION CRIT.   OTHER: Gamma-glutamyl transferase (GGT) < 3 x
                          ULN. Neutrophil count > 750/mm3.
                          International Normalized Ratio (INR) <= 1.3.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception during the study and for 90
                          days after Not breast-feeding Not pregnant.
PATIENT INCLUSION CRIT.   WEIGHT: 50 kg or more.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Over-the-counter medications, as well as
                          vitamins, dietary supplements, or holistic or
                          herbal medications, with documentation on
                          study case report form of generic medication
                          name and reason for its administration. 2.
                          Physiological glucocorticoid doses such as
                          prednisone equal to or under 7.5 mg/day or
                          its equivalent. 3. A short course (under 2
                          weeks) of pharmacologic glucocorticoid
                          therapy. 4. Vaccines may be administered at
                          the time of a study visit only after blood
                          samples have been drawn.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Virologic failure of any regimen containing
                          an HIV protease inhibitor. 2. Virologic
                          failure of more than 1 regimen containing an
                          NNRTI. 3. Participation in any DPC 083 study.
                          4. History of any coagulation disorders. 5.
                          Suicide attempt.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: 1. Use of illicit
                          intravenous drugs within 6 months of
                          initiating study treatment. 2. Current
                          alcohol or illicit drug use that, in the
                          investigator's opinion, will interfere with
                          the patient's ability to comply with the
                          dosing schedule and protocol evaluations.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any
                          investigational NNRTI. 2. Any experimental
                          drug for any indication within 30 days of
                          initiating study treatment. 3. Systemic
                          immunomodulatory agents (e.g., interferons,
                          interleukins, or thalidomide) within 30 days
                          of initiating study treatment. 4. Systemic
                          immunosuppressive agents for more than 2
                          weeks, including prior treatment (within 3
                          months of initiating treatment) with systemic
                          glucocorticoids. Physiological glucocorticoid
                          doses such as prednisone of 7.5 mg/day or
                          less or its equivalent will be allowed. 5.
                          Carbamazepine, phenytoin, or Hypericum
                          perforatum (St. John's wort) within 30 days
                          of initiating study treatment. 6. Any
                          vaccination within 3 weeks prior to
                          screening.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Non-study
                          antiretroviral medications. 2. Hydroxyurea.
                          3. Another experimental therapy. 4. Systemic
                          immunosuppressive agents. Physiological
                          glucocorticoid doses such as prednisone equal
                          to or under 7.5 mg/day or its equivalent will
                          be allowed. A short course (under 2 weeks) of
                          pharmacologic glucocorticoid therapy will be
                          allowed. 5. Systemic immunomodulatory agents
                          (e.g., interferons, interleukins, or
                          thalidomide). 6. Systemic chemotherapy or
                          systemic radiation therapy for treatment of
                          malignancy. 7. Any of the following systemic
                          medications that are potentially potent
                          inducers of the hepatic metabolism of DPC
                          083: carbamazepine, Hypericum perforatum (St.
                          John's wort), and phenytoin.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Life expectancy
                          of less than 12 months. 2. Pregnancy
                          (confirmed by a positive serum beta human
                          chorionic gonadotropin [beta-hCG] test) or
                          breast-feeding. 3. Presence of the
                          K103N/L100I double mutation in the HIV-1 RT
                          gene detected on screening HIV-1 genotype. 4.
                          Malignancy that requires systemic therapy. 5.
                          Any evidence that the patient is at immediate
                          risk of self-harm, as noted by a response
                          score of 2 or 3 in response to question
                          number 9 of the Beck Depression Inventory. 6.
                          Any clinically significant diseases (other
                          than HIV-1 infection) or clinically
                          significant findings during the screening
                          medical history or physical examination that,
                          in the investigator's or sponsor's opinion,
                          would compromise the safety of the patient or
                          the outcome of the study. 7. Difficulty
                          swallowing capsules/tablets.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0335  DPC 083
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 100 mg once daily in
                          the evening
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 100 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Until the last patient
                          enrolled has completed 48 weeks of treatment.
                          If the antiretroviral combinations are well
                          tolerated, the protocol may be amended
                          periodically to extend this study and
                          increase the total duration of dosing. The
                          study has already been extended once, from 24
                          to 48 weeks of treatment, based on a review
                          of the first 10 patients enrolled which
                          demonstrated that the drug is well-tolerated.
OTHER TREATMENT INFO.     END POINT: Safety; pharmacokinetics; and
                          efficacy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Deemed by the
                          sponsor or investigator that it is not in the
                          patient's best interest to continue. 2.
                          Entered the study in violation of the
                          protocol. 3. Required the use of long-term,
                          unacceptable concomitant medication. 4.
                          Developed a Grade 4 adverse experience (AE)
                          or repeated Grade 3 AEs. 5. Had disease
                          progression that, in the investigator's
                          opinion, precluded the patient's continued
                          participation in the study. 6. Missed 2
                          consecutive study visits or consumed less
                          than 80 percent of study medication over any
                          4-week period. 7. Met virologic failure
                          criteria (identified in protocol) and chose
                          to discontinue the study. Patients must be
                          discontinued from treatment for the following
                          reasons: 1. Withdrawal of consent. 2.
                          Pregnancy. 3. Termination of the study by the
                          sponsor.
OTHER TREATMENT INFO.     MODIFICATION: No dose adjustments of DPC 083
                          are made unless agreed upon by both the
                          sponsor and the investigator.
SUPPORTING AGENCY         DuPont Pharmaceuticals Co.
LAST REVISION DATE        20010713
CALIFORNIA                Orange Coast Med Group 361 Hosp Rd Suite 126
                          Newport Beach, CA 92663 Charles Walworth
                          [phone] Recruiting 001215.
CALIFORNIA                AIDS Healthcare Foundation 1300 North Vermont
                          Ave / Suite 606 Los Angeles, CA 90027 Charles
                          Farthing [phone] Recruiting 010713.
FLORIDA                   Saint Josephs Comprehensive Research
                          Institute 4200 N Armenia Ave / Suite 3 Tampa,
                          FL 33607 Allis Emnett [phone]
                          Recruiting 001215.
FLORIDA                   Bach and Godofsky 101 Riverfront Blvd / Suite
                          460 Bradenton, FL 34205 Debra Blanco
                          [phone] Recruiting 010713.
ILLINOIS                  Northstar Med Clinic 2835 North Sheffield Ave
                          Chicago, IL 60657 Harriett Wittert
                          [phone] Recruiting 001215.

52
UNIQUE IDENTIFIER         NIH/01348
PROTOCOL ID NUMBERS       NIAID ACTG A5077
PROTOCOL TITLE            Virologic Studies in Compartmental Samples
                          from HIV-Infected Subjects Changing or
                          Initiating Potent Antiretroviral Therapy.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To evaluate the relationship between
                          baseline viral load in blood and in nonblood
                          compartments and the time to virologic
                          failure. To evaluate the relationship between
                          viral load in nonblood compartments at the
                          time of suppression of plasma HIV-1 RNA
                          levels and the time to subsequent virologic
                          failure. To analyze the frequency of
                          detecting HIV-1 in saliva, genital
                          secretions, and lymphoid tissues from
                          patients with persistently suppressed plasma
                          HIV-1 RNA levels.
GENERAL DESCRIPTION       RATIONALE: The goal of antiretroviral therapy
                          is maximal suppression of HIV-1 replication.
                          Yet studies show that there is ongoing
                          replication of latent virus in the blood and
                          lymphoid tissues of some patients receiving
                          potent antiretroviral therapy who have had
                          suppressed plasma HIV-1 RNA levels for
                          prolonged periods of time. This continued
                          viral persistence and replication could
                          eventually result in virologic failure and
                          clinical progression as well as selection and
                          transmission of resistant HIV-1. There is a
                          need to identify, quantify, and determine
                          significance of viral reservoirs in
                          compartments other than blood. A5077 is
                          designed to evaluate the relationship between
                          viral load in blood and nonblood compartments
                          and time to virologic failure in patients
                          initiating or changing potent antiretroviral
                          therapy.
GENERAL DESCRIPTION       METHODOLOGY: Patients contribute samples of
                          blood at study entry (prior to changing or
                          initiating potent antiretroviral therapy),
                          Week 8 and every 8 weeks thereafter until
                          Week 96, and (if applicable) within 30 days
                          of confirmed virologic failure. Samples of
                          saliva and either genital secretions or
                          lymphoid tissue, or both, are collected at
                          study entry (prior to changing or initiating
                          potent antiretroviral therapy), Weeks 16, 48,
                          and 96, and within 30 days of confirmed
                          virologic failure. Clinical assessments and
                          medication updates are done at study visits.
                          Blood samples are tested for HIV-1 genotypic
                          resistance studies, HIV-1 proviral DNA
                          studies, and HIV-1 quantitation. If total
                          blood volumes exceed safe limits, blood
                          samples will not be drawn for A5077 but the
                          A5077 protocol team will request access to
                          plasma and PBMC samples from any coenrolled
                          study if applicable.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 164 patients. Accrual is
                          stratified to ensure equal enrollment of
                          males (n = 82) and females (n = 82).
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 96 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 64/164 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 20
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001102)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5077
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study;
                          Cross-Sectional Study; Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have the signed consent of a parent or legal
                          guardian if under 18 years of age. 2. Have
                          HIV-1 infection documented by any licensed
                          ELISA test kit and confirmed by either
                          Western blot, HIV-1 culture, HIV-1 antigen,
                          plasma HIV-1 RNA, or a second antibody test
                          by a method other than ELISA at any time
                          prior to study entry. 3. Have documentation
                          of a plasma HIV-1 RNA PCR or bDNA value of at
                          least 2,000 copies/ml by any of the following
                          certified methods within 60 days of study
                          entry: Chiron bDNA version 3.0; standard
                          Roche Amplicor HIV-1 Monitor assay;
                          UltraSensitive Roche Amplicor HIV-1 Monitor
                          assay; Organon Teknika Nucleic Acid
                          Sequence-Based Amplification (NASBA) HIV-1
                          RNA QT assay; or Organon Teknika NucliSens
                          HIV-1 RNA QT assay . 4. Be willing to
                          contribute samples of blood, saliva, and
                          either genital secretions or lymphoid tissue,
                          or both, at the required study visits. 5. Be
                          willing to allow the protocol team to have
                          access to results of blood tests and/or use
                          of blood samples and use of data derived from
                          clinic records and other coenrolled studies
                          (if applicable) while participating in A5077.
                          6. Have a negative urine or serum beta-HCGG
                          pregnancy test (women with reproductive
                          potential only) within 14 days of study
                          entry. Note: If a woman becomes pregnant
                          while participating in A5077, she will be
                          allowed to continue on study, but allowed
                          only to contribute blood and saliva samples
                          until the pregnancy is completed. Following
                          completion of the pregnancy, she will be
                          allowed to resume genital secretion and/or
                          lymphoid tissue collection procedures. 7.
                          Receive their primary HIV-related care at an
                          AACTG site if not enrolled in other AACTG
                          clinical trials.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test within 14 days of study entry.
PATIENT INCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Changing or
                          initiating potent antiretroviral therapy (not
                          provided by the study). Potent antiretroviral
                          therapy is defined as a minimum of 3
                          antiretroviral drugs that include any of the
                          following combinations: 2 nucleoside
                          analogues and a nonnucleoside reverse
                          transcriptase inhibitor (NNRTI); 2 nucleoside
                          analogues and abacavir; 2 nucleoside
                          analogues and a protease inhibitor (PI); 2
                          PIs and an NNRTI; 2 PIs and a nucleoside
                          analogue; or a nucleoside analogue, an NNRTI,
                          and a PI.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. A new or a
                          change in medication within 14 days prior to
                          study entry, required by active opportunistic
                          infections (OIs), opportunistic diseases,
                          intercurrent illnesses, or other infections,
                          including but not limited to active lower
                          genital tract infections. (Note: Patients who
                          require a new or a change in medication for
                          oral candidiasis or hairy leukoplakia within
                          14 days prior to study entry are not excluded
                          from participation.) 2. Immunomodulatory
                          agents within 14 days prior to study entry.
                          3. Active immunization within 14 days prior
                          to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: Active opportunistic
                          infections (OIs), opportunistic diseases,
                          intercurrent illnesses, or other infections,
                          including but not limited to active lower
                          genital tract infections, requiring a new or
                          a change in medication within 14 days prior
                          to study entry.
OTHER TREATMENT INFO.     END POINT: 1. Virologic failure (defined as
                          confirmed blood plasma HIV-1 RNA of 200
                          copies/ml or higher at Week 16 or later.
                          Patients without blood plasma HIV-1 RNA at
                          Week 16 or later will be considered virologic
                          failures at Week 16; patients without an
                          available confirmatory blood plasma viral
                          load will be considered virologic failures).
                          2. Conditional virologic failure (occurring
                          at the first of 2 successive time points at
                          Week 16 or after, where blood plasma HIV-1
                          RNA is 200 copies/ml or higher. Patients
                          without an available confirmatory blood
                          plasma viral load will be considered
                          virologic failures. If a patient does not
                          have virologic failure, the patient will be
                          considered censored at the last time point
                          with a blood plasma HIV-1 RNA measure). 3.
                          Virus detection (ability to detect virus from
                          saliva, genital secretions, and lymphoid
                          tissues).
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patient or legal
                          guardian refusal for further follow-up
                          evaluations. 2. Investigator determination
                          that further participation would be
                          detrimental to the patient's health or
                          well-being. 3. Patient failure to comply with
                          the study requirements so as to cause harm to
                          self or seriously interfere with the validity
                          of the study results. Patients who
                          discontinue the study before Week 96 must
                          have the evaluations required at Week 96
                          performed within 30 days of premature
                          discontinuation. If a study visit in which
                          compartmental evaluations was performed
                          occurred within 30 days prior to premature
                          study discontinuation, these evaluations do
                          not need to be repeated.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010205.
CALIFORNIA                San Francisco VA Med Ctr 3180 18th St San
                          Francisco, CA 941104206 Julieann Lewis
                          [phone] Recruiting 010205.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010124.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 010522.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 010522.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010316.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Ericka Patrick [phone] Recruiting
                          010517.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010316.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010502.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Charles Raines
                          [phone] Recruiting 010723.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 010423.
MISSOURI                  Washington Univ / St Louis Connect Care 4511
                          Forest Park Parkway / Suite 304 Saint Louis,
                          MO 63108 Mike Klebert [phone]
                          Recruiting 010522.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          010517.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 010627.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010522.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010213.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010410.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 010316.
RHODE ISLAND              Brown Univ / Miriam Hosp 164 Summit Ave /
                          Immunology Ctr Providence, RI 02906 Joan
                          Gormley [phone] Recruiting 010316.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010502.

53
UNIQUE IDENTIFIER         FDA/01345
PROTOCOL ID NUMBERS       FDA 313A
PROTOCOL TITLE            The Safety and Efficacy of a
                          Ritonavir-Enhanced Agenerase Regimen as
                          Salvage Therapy in HIV-Infected Individuals.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine the safety profile of a
                          ritonavir-enhanced Agenerase regimen. To
                          evaluate the efficacy of a ritonavir-enhanced
                          Agenerase regimen in patients who have failed
                          a previous nelfinavir (Viracept)-containing
                          regimen. To determine the usefulness of
                          therapeutic drug monitoring and phenotyping
                          in protease inhibitor-experienced patients.
                          Methodology: HIV-infected patients will be
                          treated with a ritonavir-enhanced Agenerase
                          regimen.
GENERAL DESCRIPTION       METHODOLOGY: HIV-infected patients will be
                          treated with a ritonavir-enhanced Agenerase
                          regimen.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (001110)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (000827)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: APV-430
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have laboratory-confirmed HIV infection and
                          be clinically stable. 2. Have plasma HIV RNA
                          of more than 1,000 copies/ml. 3. Be willing
                          and able to comply with the study
                          requirements, in the opinion of the
                          investigator. 4. Be susceptible to Agenerase.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /microL.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: amylase <= 3 x ULN; lipase <= 3 x ULN.
                          ULN (Upper Limit of Normal).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: 1. More than 12
                          weeks of prior antiretroviral treatment. 2.
                          Failure of a single protease
                          inhibitor-containing regimen containing
                          nelfinavir.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of malabsorption syndrome.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any protease
                          inhibitor other than nelfinavir. 2.
                          Agenerase.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Triazolam, astemizole, ergot medications,
                          cisapride, midazolam, bepridil, rifampin,
                          terfenadine, and pimozide. 2. Nonnucleosides.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Intolerance to
                          ritonavir. 2. Malabsorption syndrome. 3.
                          Liver disease or impairment. 4. Pancreatic
                          disease or impairment. 5. A bleeding
                          disorder. 6. Participation in another
                          investigational drug or device trial.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0258  Amprenavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
SUPPORTING AGENCY         ViroLogic Inc.
LAST REVISION DATE        20001110
TEXAS                     Joseph Gathe Private Practice 1200 Binz St /
                          Suite 120 Houston, TX 77004 Marketer
                          Washington [phone] Recruiting 001120.

54
UNIQUE IDENTIFIER         NIH/01344
PROTOCOL ID NUMBERS       NIAID ACTG A5096
PROTOCOL TITLE            Use of Single Photon Emission Computed
                          Tomography (SPECT) as a Noninvasive
                          Alternative to Liver Biopsies in Assessing
                          Liver Involvement in Subjects Coinfected with
                          HIV and Hepatitis C Virus (HCV).
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine which Single Photon
                          Emission Computed Tomography (SPECT)
                          parameters can be utilized in a staging
                          system comparable to parameters in current
                          hepatic staging systems for assessing liver
                          pathology.
GENERAL DESCRIPTION       RATIONALE: Assessment with a liver biopsy is
                          currently the standard of practice to
                          determine the status of liver involvement in
                          patients with HCV. A direct comparison
                          between SPECT results and liver pathology has
                          been examined in patients with liver disease
                          other than infectious hepatitis. SPECT has
                          been found to be more accurate than standard
                          liver-spleen scans in assessing liver
                          pathology. While current data suggest that
                          liver pathology may correlate with SPECT,
                          which specific SPECT parameters are
                          predictive of certain hepatic pathology is
                          unknown. The pilot study will compare SPECT
                          parameters with the results of liver biopsies
                          to determine the limitations of SPECT.
GENERAL DESCRIPTION       METHODOLOGY: All screened patients are
                          registered into Step 1, in which they receive
                          a radioactive tracer injection and SPECT
                          scan. Specific SPECT parameters will be
                          measured to determine a grading scale
                          corresponding to that used in liver biopsy
                          results. Some patients undergoing a second
                          liver biopsy in A5071 are enrolled into Step
                          2, with permission from protocol co-chairs,
                          in which a pregnancy test and second SPECT
                          scan are performed. Patients are reimbursed
                          for completing each SPECT scan. SPECT scans
                          or copies are reviewed to establish which
                          parameters correspond to category E of the
                          Knodell stage based on severity of fibrosis.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Natural history, Clinical
                          Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 44 patients. At least 44
                          paired liver biopsies (from A5071) and SPECT
                          scans will be enrolled in the study. Accrual
                          will consist of 23 biopsy-SPECT pair
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 72 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 36/44 010503.
PROTOCOL DETAILS          STUDY DURATION: 24 months accrual plus 72
                          weeks on study.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 11
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (001023)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5096
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have given consent for A5071 (if they are in
                          the screening process) or have enrolled in
                          A5071 and: are undergoing screening for A5071
                          and scheduled for a liver biopsy within 8
                          weeks, have had a liver biopsy within 12
                          weeks prior to enrollment in A5096, or are
                          enrolled in A5071 with plans to schedule a
                          liver biopsy within 8 weeks of having a SPECT
                          scan. 2. Intend to have a SPECT scan
                          conducted within 7 calendar days from the
                          time of A5096 registration. 3. Have a SPECT
                          scan no earlier than 2 weeks after the liver
                          biopsy but within 8 weeks of the liver biopsy
                          (if SPECT scan is not conducted prior to the
                          liver biopsy). Note: Patients off drug/on
                          study in A5071 and planning to have a liver
                          biopsy within 8 weeks are still eligible.
                          Note: Patients who have had the liver biopsy
                          and SPECT scan performed during screening for
                          A5071 but do not enter A5071 are still
                          eligible. The pathology will be obtained for
                          central review. In this circumstance, the
                          A5096 co-chairs should be contacted for
                          details on obtaining central pathology
                          readings on liver biopsies.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          Allergy or sensitivity to technetium Tc 99m
                          sulfur colloid or other technetium sulfur
                          colloids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          condition are excluded: Allergy or
                          sensitivity to technetium Tc 99m sulfur
                          colloid or other technetium sulfur colloids.
OTHER TREATMENT INFO.     END POINT: Histology (numeric score for
                          Category E of the Knodell HAI); and SPECT
                          (parameters to be measured: intrahepatic
                          shunted blood flow, intrahepatic shunt index,
                          total hepatic blood flow, liver and spleen
                          volumes, spleen-to-liver uptake ratio, bone
                          marrow-to-liver uptake ratio, left-to-right
                          hepatic lobe uptake ratio, and liver
                          heterogeneity).
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patients register
                          for A5096 but do not receive a SPECT scan or
                          liver biopsy within the required time frames.
                          2. Discontinuation from A5071 (off study). 3.
                          Pregnancy. 4. Patient request. 5. Request of
                          the primary care provider if she/he thinks
                          the study is no longer in the best interest
                          of the patient. 6. Clinical reasons believed
                          life-threatening by the physician. 7. Patient
                          is judged by the investigator to be at
                          significant risk of failing to comply with
                          the provisions of the protocol so as to cause
                          harm to self or seriously interfere with the
                          validity of the study results.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010119.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010118.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010222.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 010228.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010323.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010118.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 001215.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010222.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] No longer recruiting 010417.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Chip
                          Lohner [phone] Recruiting 010316.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010323.

55
UNIQUE IDENTIFIER         NIH/01341
PROTOCOL ID NUMBERS       NIAID ACTG P1020-A
PROTOCOL TITLE            Phase I/II, Open-Label, Pharmacokinetic and
                          Safety Study of a Novel Protease Inhibitor
                          (BMS 232632) in Combination Regimens in
                          Antiretroviral Therapy (ART)-Naive and
                          -Experienced HIV-Infected Infants, Children,
                          and Adolescents.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Treatment IND
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To determine the pharmacokinetic
                          profile and dosing schedule of the capsule
                          formulation for BMS-232632 in combination
                          with 2 nucleoside reverse transcriptase
                          inhibitors (NRTIs) in HIV-infected children
                          and adolescents. To determine the
                          pharmacokinetic profile and dosing schedule
                          of the powder formulation for BMS-232632 in
                          combination with 2 NRTIs in HIV-infected
                          infants and young children. To determine the
                          safety and tolerability of BMS-232632 in
                          HIV-infected infants, children, and
                          adolescents.
GENERAL DESCRIPTION       RATIONALE: Advancements in antiretroviral
                          drug treatments for HIV-infected children and
                          adolescents are hindered by patient
                          non-adherence. The availability of a powder
                          formulation and the once-daily dosing
                          schedule makes BMS-232632 an attractive agent
                          for improved adherence in pediatric treatment
                          regimens. This study is designed to provide
                          pharmacokinetic data to guide dosing
                          recommendations for BMS-232632 in infants,
                          children and adolescents. During the study,
                          the safety and tolerance of BMS-232632 will
                          be closely monitored, and preliminary
                          virologic efficacy data will be obtained.
GENERAL DESCRIPTION       METHODOLOGY: All patients receive the study
                          drug BMS-232632 once a day with 2 other
                          antiretroviral drugs (not provided by the
                          study). Patients are stratified into 1 of 4
                          groups with respect to age and study drug
                          formulation. Patients in Group 1 are infants
                          age 3 months and 1 day up to 2 years and take
                          BMS-232632 in powder form. Patients in Groups
                          2 and 3 are children age 2 years and 1 day up
                          to 13 years. Group 2 receives BMS-232632 in
                          powder form, while Group 3 receives the
                          capsule form. Patients in Group 4 are
                          adolescents age 13 years and 1 day up to 21
                          years and take BMS-232632 in capsule form.
                          Enrollment starts with 5 patients per
                          stratum. Patients within each stratum are
                          evaluated for pharmacokinetic and safety
                          criteria. The dose may be adjusted until one
                          is found that passes both sets of criteria,
                          then 5 additional patients are enrolled.
                          Enrollment continues for each stratum once
                          all patients within that stratum meet the
                          pharmacokinetics criteria. Patients continue
                          in the study until the last patient to enroll
                          in the study has reached Week 96 of his/her
                          treatment. Patients visit the clinic every 4
                          weeks through Week 48, then every 8 weeks. At
                          every visit, a complete medical history and
                          physical exam is performed, and urine and
                          blood samples are collected. Patients of
                          childbearing age have a pregnancy test
                          performed at each visit.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          safety, Drug tolerance, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 72 patients. Minimum of 72
                          patients. Four groups with at least 18
                          patients each.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 96 weeks after
                          the last patient is enrolled.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 38/72 010731.
PROTOCOL DETAILS          STUDY DURATION: 96 weeks after the last
                          patient is enrolled.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 40
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (001117)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1020-A
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Dose-Response Design
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have a confirmed diagnosis of HIV infection
                          defined by the current definition of the
                          PACTG Virology Core Laboratory Committee. The
                          current (April 00) definition requires 2
                          positive assays from 2 different samples [AS
                          PER AMENDMENT 11/17/00: 2 positive peripheral
                          blood samples from different days]. The 2
                          results may be in any combination of the
                          following: at any age -- DNA PCR or HIV
                          culture [AS PER AMENDMENT 11/17/00: HIV
                          culture, HIV-DNA PCR, or plasma HIV RNA of
                          10,000 copies/ml or higher]; age greater than
                          4 weeks -- p24 antigen detection [AS PER
                          AMENDMENT 11/17/00: neutralizable HIV p24
                          antigen (regular or ICD)]; and age greater
                          than 18 months -- licensed ELISA with
                          confirmatory Western blot. [AS PER AMENDMENT
                          11/17/00: At least 1 of the above tests must
                          be completed in an ACTG-certified laboratory,
                          which is approved to perform the assay for
                          protocol testing.] This definition may be
                          updated by the PACTG Virology Core Laboratory
                          Committee at any time. This study will update
                          the sites if these assays or their
                          combination is modified. The protocol will
                          always use the current definition of
                          confirmed HIV infection. 2. Have any Centers
                          for Disease Control and Prevention (CDC)
                          clinical classification and immune status. 3.
                          Be antiretroviral treatment-naive or
                          -experienced. Patients must be able to add 2
                          new NRTIs as part of their new therapy in
                          this protocol, or have genotypic evidence of
                          sensitivity to 2 NRTIs (the NRTIs must be
                          used in combinations recommended in the
                          Guidelines for the Use of Antiretroviral
                          Agents in Pediatric and Adolescent HIV
                          Infection). If the patient has previously
                          received treatment with zalcitabine,
                          didanosine (ddI) will not be considered a new
                          NRTI for his/her new regimen under this
                          protocol, and vice-versa. Abacavir will be
                          excluded as 1 of the NRTI options for the
                          patient's regimen. 4. Show evidence of
                          retained phenotypic sensitivity to BMS-232632
                          (resistance index ratio of less than 10) when
                          the patient has failed (after at least 12
                          weeks of therapy) 2 or more courses of
                          PI-containing regimens. 5. Have demonstrated
                          ability and willingness to swallow study
                          medications. 6. Have signed consent of parent
                          or guardian if under 18 years of age. 7. Have
                          a viral load of 5,000 copies/ml or higher,
                          confirmed by PACTG Virology Core Central
                          Laboratory.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. Any
                          medication prescribed by the patient's
                          clinician that is not disallowed by the
                          study. 2. Intravenous gamma globulin
                          treatment. 3. Chronic steroids. 4. Rifampin
                          will be allowed only with dose adjustment, if
                          needed, and permission by the study team
                          prior to entering the study. The team should
                          be notified of these patients after the
                          screening visit. The study chair will discuss
                          each case with the team and determine if the
                          patient may participate after the rifampin
                          dose has been adjusted.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 03
                          months less than or equal to 21 years.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Treatment with
                          any of the following within 180 days prior to
                          study entry: anabolic steroids, megestrol
                          acetate, interleukin, interferon,
                          thalidomide, or growth hormone.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Abacavir
                          will be excluded as 1 of the NRTIs for the
                          patient's regimen. 2. Antiretroviral
                          therapies other than the regimens described
                          in this study. 3. Investigational drugs. 4.
                          Systemic cytotoxic chemotherapy. 5. Chronic
                          acetaminophen use, defined as more than 3
                          doses per day, for more than 7 days. 6.
                          Treatment with any of the following:
                          alprazolam, amiodarone, astemizole, bepridil,
                          bupropion, carbamazepine, cisapride,
                          clorazepate, clozapine, diazepam,
                          dexamethasone, encainide, estazolam, ergot
                          alkaloids and derivatives, flecainide
                          acetate, flurazepam, ketoconazole,
                          isotretinoin, itraconazole, meperidine,
                          midazolam, phenobarbital, phenytoin,
                          pimozide, piroxicam, propafenone,
                          propoxyphene, quinidine, rifabutin,
                          terfenadine, triazolam, or zolpidem. 7.
                          Grapefruit juice for the duration of the
                          study, as per dosing directions given by
                          Bristol-Myers Squibb (BMS). [8. AS PER
                          AMENDMENT 11/17/00: ddI once daily.].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Active hepatitis.
                          2. Acute serious/invasive infection requiring
                          therapy at the time of enrollment. 3. Active
                          malignancy requiring chemotherapy. 4. Any
                          clinically significant diseases (other than
                          HIV infection) or clinically significant
                          findings during the screening medical history
                          or physical examination that, in the
                          clinician's opinion, would compromise the
                          outcome of this study. 5. Any laboratory or
                          clinical toxicity of at least Grade 2 at
                          study entry. 6. Hypersensitivity to any
                          component of the formulation of BMS-232632.
                          7. Co-enrollment in PACTG 299, PACTG 265,
                          PACTG 391, or PACTG 1011.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0314  BMS-232632
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Starting dose: 310
                          mg/m2 qd in the morning.
                          Pharmacokinetics-based dose adjustments may
                          be made to a maximudose of 400 mg/m2 qd in
                          the morning
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, powder and
                          capsule formulations
OTHER TREATMENT INFO.     TREATMENT DURATION: 96 weeks after the last
                          patient is enrolled.
OTHER TREATMENT INFO.     END POINT: To determine the pharmacokinetic
                          profile and optimal dosing schedule of the
                          capsule and powder formulations of BMS-232632
                          in combination with 2 NRTIs in HIV-infected
                          infants, children, and adolescents.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Drug toxicity
                          according to protocol guidelines. 2. Need of
                          treatment not allowed in the study. 3.
                          Pregnancy or breast-feeding. 4. Treatment
                          failure, as defined in the protocol. If the
                          protocol chair, the site investigator, and
                          the patient's caregiver decide that it is in
                          the best interest of the child to stay on
                          his/her current treatment, he/she will be
                          allowed to continue on the study. 5.
                          Investigator determines that further
                          participation would be detrimental to the
                          patient's health or well-being. 6.
                          Non-compliance. 7. Patient and/or guardian
                          refuses further treatment and/or follow-up
                          evaluations.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                UCLA Med Ctr 10833 Le Conte Ave Los Angeles,
                          CA 90095 Maryanne Dillon [phone]
                          Recruiting 010119.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 010406.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 010222.
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 010119.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Mary Caffery [phone]
                          Recruiting 010503.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Maryanne Dillon
                          [phone] Recruiting 010627.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 010418.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Julie Ziegler
                          [phone] Recruiting 010316.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 010222.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 010228.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          010502.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Lucrecia Rios [phone]
                          Recruiting 010517.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699
                          Margaret Cowie [phone] Recruiting
                          001129.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Kirk
                          Bertelsen [phone] Recruiting 010410.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 001110.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 010517.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 010318.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 010502.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 010410.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Lisa Cerrachio
                          [phone] Recruiting 010406.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 001110.
NEW YORK                  Montefiore Medical / AECOM 1300 Morris Park
                          Ave Bronx, NY 19461 Gayle Kreinik
                          [phone] Recruiting 010723.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 001129.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Shailaja Kancherla Recruiting 010117.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010418.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 010207.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 001110.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 010423.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 010406.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 010502.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          010117.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 001110.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          010207.
PENNSYLVANIA              Saint Christopher's Hosp for Children Erie
                          Ave at Front St Philadelphia, PA 191341095
                          Roslynn Buie [phone] Recruiting 010418.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Anne Cope [phone] Recruiting
                          010418.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          001110.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 010406.
VIRGINIA                  Children's Hosp of the King's Daughters 601
                          Children's Lane Norfolk, VA 23507 Donna
                          Sandifer [phone] Recruiting 001110.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 010124.

56
UNIQUE IDENTIFIER         NIH/01339
PROTOCOL ID NUMBERS       NIAID ACTG A5078
PROTOCOL TITLE            Carotid Artery Intima-Media Thickness in
                          HIV-Infected and Uninfected Adults: A Pilot
                          Study.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: Cross-Sectional: To compare
                          differences in the baseline intima-media
                          thickness (IMT) of the carotid artery between
                          HIV-infected participants receiving protease
                          inhibitor (PI)-containing regimens and
                          participants not receiving PI-containing
                          regimens (Group 1 versus Group 2). To compare
                          differences in the baseline IMT of the
                          carotid artery between HIV-infected
                          participants and HIV-negative participants
                          (Group 2 versus Group 3 or Group 1 and Group
                          2 versus Group 3 as appropriate).
                          Longitudinal: To compare the rate of change
                          in the IMT of the carotid artery between
                          HIV-infected participants receiving
                          PI-containing regimens and participants not
                          receiving PI-containing regimens (Group 1
                          versus Group 2). To compare the rate of
                          change in IMT of the carotid artery between
                          HIV-infected participants and HIV-negative
                          participants (Group 2 versus Group 3 or Group
                          1 and Group 2 versus Group 3 as appropriate).
GENERAL DESCRIPTION       RATIONALE: Determination of clinical, lipid,
                          and nonlipid risk factors has traditionally
                          been the approach for gauging an individual's
                          risk for coronary artery disease (CAD).
                          However, low-cost, noninvasive carotid artery
                          IMT has been found to demonstrate correlation
                          with CAD as good or better than lipid and
                          nonlipid risk factors. This study will
                          attempt to identify the role of PI therapy
                          and HIV infection on the risk of development
                          of subclinical atherosclerosis by comparing
                          carotid IMT among study groups.
GENERAL DESCRIPTION       METHODOLOGY: Three groups are studied. Group
                          1 is composed of HIV-positive participants
                          who receive a PI-containing regimen. Group 2
                          is composed of HIV-positive participants who
                          do not receive a PI-containing regimen. Group
                          3 is composed of HIV-negative participants.
                          Participants at each site are enrolled into a
                          triad consisting of an individual from each
                          group. Each member of the triad is closely
                          matched by gender, age, smoking and
                          menopausal status, race, and normal or
                          hypertensive blood pressure. All 3 members of
                          the triad must be identified before they are
                          registered to the study. All participants
                          visit the clinic every 24 weeks for 96 weeks.
                          At each visit, participants have a physical
                          exam, a medical history covering the time
                          since their last visit, blood tests for
                          fasting lipids and glucose, and an IMT test.
                          The absolute value for carotid IMT is
                          compared among the 3 groups. Viral load and
                          CD4 counts are measured in Groups 1 and 2
                          participants. At Week 96 (the last visit)
                          participants in Group 3 are tested for HIV.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Adverse effects, Drug therapy,
                          Natural history.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 132 patients. Three groups
                          of 44 participants each.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately 2
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 42/132 010731.
PROTOCOL DETAILS          STUDY DURATION: 9 months enrollment plus 2
                          years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010427)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5078
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study;
                          Cross-Sectional Study; Longitudinal Study;
                          Matched-Pair Design; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants in
                          Groups 1 and 2 must have: 1. HIV-1 infection
                          as documented by any licensed ELISA test kit
                          and confirmed by either Western blot, HIV-1
                          culture, HIV-1 antigen, plasma HIV-1 RNA, or
                          a second antibody test by a method other than
                          ELISA at any time prior to study entry. 2. An
                          HIV-1 RNA plasma level of 10,000 copies/ml or
                          less. 3. A negative pregnancy test within 60
                          days prior to study entry. Participants in
                          Group 3 must have: HIV-1 negativity as
                          documented by a licensed ELISA test kit
                          within 60 days of study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Body mass index (BMI) <= 30. Fasting
                          glucose level <= 126 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required for participants
                          in Group 1: At least 1 PI therapy for 2 or
                          more years of continuous use prior to study
                          entry. Participants who received 2 or more
                          PIs must have a total combined duration of
                          continuous exposure for 2 or more years. [AS
                          PER AMENDMENT 4/27/01: Interruptions in
                          therapy for 4 weeks or less for management of
                          toxicity or to change therapy are allowed.
                          Participant's statement is sufficient for
                          documentation of prior receipt of PIs.]
                          Required for participants in Group 2:
                          Treatment for at least 6 consecutive months
                          sometime in the past (documentation
                          required), if not currently receiving
                          therapy.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: [Allowed: AS PER
                          AMENDMENT 04/27/01: Replacement therapy for
                          hypothyroidism if TSH level is normal.]
                          Required for participants in Group 1: At
                          least 1 PI therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Participants with
                          the following prior conditions are excluded:
                          1. Cardiovascular disease [AS PER AMENDMENT
                          4/27/01: (including a history of angina,
                          myocardial infarction, or abnormal stress
                          test), stroke], diabetes, renal disease,
                          liver disease, and hypothyroidism by
                          thyroid-stimulating hormone testing. [AS PER
                          AMENDMENT 4/27/01: Liver disease is no longer
                          an exclusion. Participants with a history of
                          hypothyroidism who are on replacement therapy
                          and have a normal TSH are eligible to
                          enroll.] 2. Family history of myocardial
                          infarctions prior to age 55 for first-degree
                          male relatives and age 65 for first-degree
                          female relatives. First degree is defined as
                          parents, brothers, sisters, or children.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence which, in the
                          opinion of the investigator, would interfere
                          with adherence to study requirements.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: [Excluded: AS PER
                          AMENDMENT 4/27/01: Radiation therapy.].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: [Excluded: AS PER AMENDMENT
                          4/27/01: Systemic steroids (prednisone or the
                          equivalent) at doses greater than 5 mg/day
                          for more than 30 consecutive days.] Excluded
                          for participants in Group 2: Any
                          PI-containing antiretroviral therapies for 3
                          months or more at any time prior to study.
                          [AS PER AMENDMENT 4/27/01: Participant's
                          statement is sufficient for documentation on
                          lack of receipt of PIs.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: [Excluded: AS PER
                          AMENDMENT 4/27/01: 1. Oral hypoglycemia
                          agents and/or thiazolidinediones. 2. Systemic
                          chemotherapy. 3. Systemic steroids
                          (prednisone or the equivalent) at doses
                          greater than 5 mg/day for more than 30
                          consecutive days.] Excluded for participants
                          in Group 2: Any PI-containing antiretroviral
                          therapies. Participants should not be
                          planning to initiate therapy with a PI in the
                          upcoming months. The team understands that
                          the need for PI therapy could change during
                          the course of the study but would like to
                          avoid enrolling participants who are planning
                          on starting a PI. [AS PER AMENDMENT 4/27/01:
                          Participant's statement is sufficient for
                          documentation on lack of receipt of PIs.].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Participants with the
                          following symptoms or conditions are
                          excluded: 1. Cardiovascular disease [AS PER
                          AMENDMENT 4/27/01: (including a history of
                          angina, myocardial infarction, or abnormal
                          stress test), stroke], diabetes, renal
                          disease, liver disease, and hypothyroidism by
                          thyroid-stimulating hormone testing. [AS PER
                          AMENDMENT 4/27/01: Liver disease is no longer
                          an exclusion. Participants with a history of
                          hypothyroidism who are on replacement therapy
                          and have a normal TSH are eligible to
                          enroll.] 2. Chronic illness, defined as
                          requiring systemic therapy, with the
                          exception of hypertension. 3. Uncontrolled
                          hypertension. 4. Obesity defined as body mass
                          index (BMI) greater than 30.
OTHER TREATMENT INFO.     END POINT: Cross-Sectional: Carotid artery
                          IMT at baseline [AS PER AMENDMENT 4/27/01:
                          (average of entry and Week 1 evaluations)].
                          Longitudinal: Carotid artery IMT at Weeks 24,
                          48, 72, and 96.
OTHER TREATMENT INFO.     DISCONTINUE: Participants may be discontinued
                          for the following reasons: 1. Investigator's
                          decision that continuing in the study would
                          be harmful to the health of the participant.
                          2. Participant is unable to keep
                          appointments. 3. Administrative reasons. 4.
                          Participant's requirement for disallowed
                          treatment.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 001229.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 001229.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 001229.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Mario Guerrerro
                          [phone] Recruiting 010111.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010111.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 001229.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] Recruiting 010406.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 001229.

57
UNIQUE IDENTIFIER         NIH/01337
PROTOCOL ID NUMBERS       NIAID ACTG A5072
PROTOCOL TITLE            Evaluation of the Relationship Between
                          Immunologic Recovery After Highly Active
                          Antiretroviral Therapy and the Ability to
                          Mobilize CD34+ Stem Cells Following G-CSF
                          Administration.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To determine whether stem cell
                          reserves present prior to initiation of
                          highly active antiretroviral therapy (HAART)
                          predict subsequent immunologic recovery after
                          maximal viral suppression. To determine the
                          effect of maximally suppressive
                          antiretroviral therapy on stem cell reserves.
GENERAL DESCRIPTION       RATIONALE: In HIV infection, a progressive
                          decline and/or dysfunction of several cell
                          types is seen. It is thought that stem cell
                          dysfunction or destruction may contribute to
                          the hematologic and immunologic perturbations
                          characteristic of HIV infection and may
                          possibly limit the extent of immunologic
                          recovery following HAART. This study proposes
                          to investigate whether stem cell function and
                          reserves are important in determining the
                          extent of immune reconstitution following
                          HAART.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified
                          according to CD4 count. On Day 0, patients
                          receive a 7-day cycle of subcutaneous
                          granulocyte colony-stimulating factor
                          (G-CSF). Blood samples are collected
                          regularly, and on Day 14 patients undergo
                          real-time HIV-1 RNA determinations. On Day
                          28, or sooner if HIV RNA is at least 1 log
                          above baseline on Day 14, HAART consisting of
                          daily receipt of abacavir, lamivudine,
                          amprenavir, and ritonavir is initiated and
                          continues until Week 76. Patients who achieve
                          viral suppression (below 400 copies/ml of
                          plasma HIV-1 RNA) by Week 26 are eligible to
                          receive a second 7-day cycle of G-CSF at Week
                          28 and, if viral suppression continues
                          through Week 50, a third cycle of G-CSF at
                          Week 52. Patients are followed every 8 weeks
                          for changes in viral load. Additionally,
                          patients are monitored at regular intervals
                          for surrogate markers of immunologic recovery
                          and, during each cycle of G-CSF, for
                          measurements of stem cell mobilization.
                          Patients may also volunteer for A5085s (Bone
                          Marrow Aspirate Substudy) at participating
                          sites.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy,
                          Immunology, Clinical Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 46 patients. 23 per
                          stratum.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 76 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/46.
PROTOCOL DETAILS          STUDY DURATION: Approximately 100 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010423)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5072. Substudy
                          ACTG A5085s
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2. Be a good
                          candidate, in the investigator's opinion, for
                          initiating antiretroviral therapy. 3. Have a
                          plasma HIV-1 RNA level of 1,000 copies/ml or
                          more within 28 days prior to study entry
                          performed at Johns Hopkins University using
                          the Roche Amplicor HIV-Monitor assay. 4. Have
                          a documented CD4+ count of 500 cells/mm3 or
                          less within 28 days prior to study entry.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.1 g/dl for men and > 8.9 g/dl
                          for women. Within 28 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3 Within 28 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 500 cells/mm3 Within
                          28 days prior to study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN ULN (Upper Limit of
                          Normal). Within 28 days prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 28 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 28 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN Within 28 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Not pregnant
                          Negative pregnancy test within 7 days of
                          study entry.
PATIENT INCLUSION CRIT.   OTHER: The main study has been approved for
                          prisoner participation.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Acupuncture
                          and visualization techniques.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Maintenance or chemoprophylaxis for
                          opportunistic infections including
                          Pneumocystis carinii pneumonia (which is
                          recommended for all patients who have a CD4+
                          cell count below 200 cells/mm3). 2.
                          Antibiotics and topical, and/or oral,
                          antifungal agents as medically indicated. 3.
                          Regularly prescribed antipyretics,
                          analgesics, allergy medications,
                          antidepressants, sleep medications, oral
                          contraceptives, megestrol acetate,
                          testosterone, etc., as medically indicated.
                          4. Alternative non-prescription therapies
                          such as vitamins (except for vitamin E) and
                          herbal treatments (except St. John's wort).
                          5. Recombinant erythropoietin (rEPO). Allowed
                          with caution: Baycol (with RTV); carbolith,
                          cytotoxic chemotherapy, eskalith, lithane,
                          and lithium (with G-CSF); cerivastatin and
                          sildenafil (with APV and RTV); and oral
                          contraceptives and rifabutin (with NFV).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Malignant neoplastic disease. 2. Any medical
                          condition which, in the investigator's
                          opinion, would interfere with evaluation of
                          the patient.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence which, in the
                          investigator's opinion, would interfere with
                          adherence to study requirements.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Treatment for
                          an opportunistic infection within 14 days
                          prior to study entry. 2. G-CSF or GM-CSF
                          within 180 days prior to study entry. 3. More
                          than 2 weeks of prior antiretroviral therapy
                          or any antiretroviral therapy within 90 days
                          of study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Agents
                          with immunomodulating potential including but
                          not limited to: thalidomide, interferons,
                          interleukins, pentoxifylline,
                          dinitrochlorobenzene, thymosin alpha 1,
                          thymopentin, inosiplex, polyribonucleoside,
                          ditiocarb sodium, HIV or other vaccines
                          (except if medically warranted as in flu,
                          pneumococcal, and hepatitis B vaccines),
                          hydroxyurea, and systemic IV or oral
                          corticosteroids. 2. GM-CSF (sargramostim) or
                          non-study provided G-CSF (filgrastim). 3.
                          Systematic cancer chemotherapy. 4.
                          Investigational agents not specified
                          otherwise, without study personnel approval.
                          5. Antiretroviral medications that are not
                          part of the study. 6. Drug-specific
                          prohibited concomitant medications as
                          specified in the protocol.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Malignant
                          neoplastic disease. 2. Hypersensitivity to E.
                          coli-derived proteins (e.g., Humulin [an
                          insulin] or human growth hormones [Humatrope,
                          Nutropin, Protropin, etc.]). Such
                          hypersensitivity reactions (i.e.,
                          anaphylactic reaction, bronchospasm) could
                          occur with exposure to E. coli-derived
                          products such as filgrastim. 3. Medical
                          condition which, in the opinion of the site
                          investigator, would interfere with the
                          evaluation of the patient. 4. Treatment of a
                          serious opportunistic infection.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0258  Amprenavir
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0086  Filgrastim
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 300 mg bid. Drug 2:
                          150 mg bid. Drug 3: 600 mg bid. Drug 4: 100
                          mg bid. Drug 5: 10 microg/kg daily for 7-day
                          cycle at Day 0, Week 28, aWeek 52
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 300 mg.
                          Drug 3: 1200 mg. Drug 4: 200 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 300-mg tablets.
                          Drug 2: Oral, 150-mg tablets. Drug 3: Oral,
                          150-mg capsules. Drug 4: Oral, 100-mg soft
                          gel capsules. Drug 5: Subcutaneous
OTHER TREATMENT INFO.     TREATMENT DURATION: Approximately 76 weeks
                          (HAART from Weeks 4 to 76; G-CSF at Week 0
                          and possibly Weeks 28 and 52).
OTHER TREATMENT INFO.     END POINT: Stem cell reserves present prior
                          to initiation of HAART (AUC for CD34+ cells
                          from Days 1-14 after administration of
                          G-CSF); and immunologic recovery in patients
                          who achieve maximal viral suppression of
                          post-HAART (change in CD4+ cell count from
                          baseline to 24 weeks after the institution of
                          HAART, and the change in CD3+/CD4+/CD45RA+
                          (naive) cell count from baseline to 24 weeks
                          after the institution of HAART).
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Two consecutive
                          plasma HIV-1 RNA levels greater than or equal
                          to 400 copies/ml after completion of 22 weeks
                          of antiretroviral therapy (Week 26). 2.
                          Inability to take G-CSF for any reason and/or
                          omission of a G-CSF dose. 3. Discontinuation
                          of antiretroviral therapy for a total of more
                          than 7 consecutive days. 4. Inability to take
                          either the initial combination antiretroviral
                          regimen offered by the study or the
                          alternative drugs listed for NRTI and PI
                          toxicities. 5. Patient refusal of further
                          treatment. 6. Determination by the local
                          investigator and/or protocol chair(s) that
                          further participation in the study would be
                          detrimental to the patient's health or
                          well-being. 7. Requirement for disallowed
                          medications. 8. Pregnancy 9. Any new
                          AIDS-defining illness or condition that
                          results in an inability to administer study
                          medications or prevents the patient from
                          attending follow-up visits. 10. Drug
                          toxicity.
OTHER TREATMENT INFO.     MODIFICATION: Dose reductions for study
                          medications will not be allowed.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010618.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010618.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 010618.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] No longer recruiting 010612.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] No longer recruiting
                          010627.

58
UNIQUE IDENTIFIER         NIH/01336
PROTOCOL ID NUMBERS       NIAID ACTG A5029
PROTOCOL TITLE            Assessment of Prevalence and Persistence of
                          Human Papilloma Virus (HPV) DNA in
                          HIV-Infected Women Who Are Antiretroviral
                          Naive and Have Initiated HAART.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To estimate the prevalence of human
                          papillomavirus (HPV) DNA at baseline among
                          HIV-infected women who are antiretroviral
                          naive. To estimate the rate of conversion to
                          negative HPV DNA after 48 weeks among
                          HIV-infected women who were HPV DNA positive
                          at baseline and responded to treatment with
                          highly active antiretroviral therapy (HAART)
                          through Year 1 (Week 48).
GENERAL DESCRIPTION       RATIONALE: HIV infection is a significant
                          risk factor for human HPV infection and the
                          development of HPV-associated lesions in the
                          female genital tract. Findings suggest that
                          HIV infection and/or HIV-related
                          immunosuppression increases a woman's
                          susceptibility to HPV infection or alters the
                          natural history of preexisting HPV infection.
                          Treatment with HAART has been shown to result
                          in significant increases in CD4+ cell counts
                          and partial reconstitution of the immune
                          system. It is not known whether treatment of
                          HIV infection with potent antiretroviral
                          regimens could affect the persistence of HPV
                          infection and progression of cervical
                          dysplasia. This study is important for
                          HIV-infected women because of the
                          implications for gynecologic management and
                          determination of cervical disease risk.
GENERAL DESCRIPTION       METHODOLOGY: At baseline, Weeks 24 and 48,
                          and then every 48 weeks until study
                          completion, women undergo pelvic examination
                          and cervical specimens collection by the
                          following methods: 1) Sno-strip; 2)
                          cervicovaginal lavage; 3) cervical brush
                          method; and 4) Pap smear. A colposcopy is
                          required for any woman who has an abnormal
                          Pap smear reading unless the abnormal Pap
                          smear is thought to be due to an intercurrent
                          infection. A cervical biopsy is strongly
                          recommended in the event of an abnormal
                          colposcopy. Blood is collected for HPV
                          antibody testing, viral load, and CD4
                          measures.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Clinical
                          Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 160 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until 144 weeks
                          after last patient is enrolled (approximately
                          3 to 5 years).
PROTOCOL DETAILS          ACTUAL ACCRUAL: 25/160 010724.
PROTOCOL DETAILS          STUDY DURATION: 27 months plus 144 weeks of
                          follow-up of last enrolled patient (
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 26
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (000918)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5029
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Women must: 1.
                          Have HIV-1 infection documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2. Be willing
                          to enroll in an AACTG, PACTG, or a
                          non-AACTG/PACTG pharmaceutical
                          company-sponsored antiretroviral trial that
                          provides HAART to the enrolled patients and
                          is a Phase II study or higher. 3. Have
                          written consent of a parent or guardian if
                          under 18 years.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Menstruating.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Women must
                          be willing to enroll in an AACTG, PACTG, or a
                          non-AACTG/PACTG pharmaceutical
                          company-sponsored antiretroviral treatment
                          trial that provides HAART to the enrolled
                          patients and is a Phase II study or higher.
                          Allowed: 1. Systemic corticosteroid treatment
                          for physiologic replacement. 2. Topical
                          imiquimod (Aldara) (other than intravaginal).
                          3. Intralesional interferon. 4. External
                          topical cidofovir and intralesional
                          cidofovir. 5. Topical administration of
                          5-fluorouracil.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Women with the
                          following prior conditions are excluded: 1.
                          Invasive cervical cancer. 2. Participation in
                          HPV vaccine trials.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence which, in the
                          opinion of the investigator, would interfere
                          with adherence to study requirements.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Greater than
                          14 days of any antiretroviral treatment at
                          any time since HIV diagnosis. 2. Any
                          immunomodulating, anti-HPV, and
                          investigational agents, except for unapproved
                          antiretroviral drugs provided by coenrollment
                          into a Phase II or III trial with approval
                          from an A5029 chair within 30 days of study
                          entry including, but not limited to, systemic
                          interferons, interleukins (or other
                          cytokines), thalidomide, thymopentin,
                          systemic cidofovir, HPV vaccines,
                          hydroxyurea, and granulocyte
                          colony-stimulating factor (G-CSF, filgrastim)
                          and GM-CSF (sargramostim).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Chronic
                          corticosteroid administration at
                          supraphysiologic doses. 2. Receipt of any
                          immunomodulating, investigational, or
                          anti-HPV agents, including but not limited to
                          the following: systemic interferons and
                          interleukins (or other cytokines),
                          thalidomide, thymosin alpha 1 (thymosin
                          alpha), thymopentin, systemic cidofovir, HPV
                          vaccines, hydroxyurea, G-CSF(filgrastim),
                          GM-CSF (sargramostim), and intravaginal
                          imiquimod (Aldara).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Women with the following
                          conditions are excluded: 1. Hysterectomy. 2.
                          Invasive cervical cancer. 3. Participation in
                          HPV vaccine trials.
OTHER TREATMENT INFO.     END POINT: 1) HPV DNA status
                          (positive/negative) at baseline (study entry
                          visit). 2) Conversion rate from positive HPV
                          DNA status at baseline (study entry visit) to
                          negative HPV DNA status at Year 1 (Week 48).
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patient or legal
                          guardian refusal to adhere to the study
                          requirements as determined by the
                          investigator. 2. Investigator determination
                          that further participation would be
                          detrimental to the patient's health or
                          well-being. 3. Patient failure to comply with
                          the study requirements so as to cause harm to
                          self or seriously interfere with the validity
                          of the study results. 4. Failure by women who
                          register to A5029 to initiate HAART regimen.
                          5. Patient request.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 010108.
CALIFORNIA                San Francisco VA Med Ctr 3180 18th St San
                          Francisco, CA 941104206 Julieann Lewis
                          [phone] Recruiting 010115.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010118.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010119.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 010318.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010119.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010522.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010612.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010119.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010119.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010119.
MASSACHUSETTS             Brigham and Women's Hosp Div of Infectious
                          Diseases / 15 Francis St PBB A-4 Boston, MA
                          02215 Carolyn Koziol [phone] Recruiting
                          010731.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 010109.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010118.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 001121.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010323.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 010108.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 010731.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 010119.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010108.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Felipe Pabon [phone]
                          Recruiting 010424.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010119.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 010118.
RHODE ISLAND              Brown Univ / The Miriam Hosp 164 Summit Ave /
                          Research Building / Room 215 Providence, RI
                          02906 Joan Gormley [phone] Not yet
                          recruiting 010118.
RHODE ISLAND              Brown Univ / Miriam Hosp 164 Summit Ave /
                          Immunology Ctr Providence, RI 02906 Joan
                          Gormley [phone] Recruiting 010118.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 010316.

59
UNIQUE IDENTIFIER         NIH/01335
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-04-006
PROTOCOL TITLE            A Phase I/II Safety and Immunogenicity
                          Evaluation of a Prime/Boost Vaccine Using
                          ALVAC-HIV (vCP 1452) with Recombinant gp160
                          LAI/MN-2 in HIV-Infected Subjects Treated
                          with Antiretroviral Therapy for a Minimum of
                          2 Years.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Therapeutic AIDS Vaccine
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          immunogenicity of 2 investigational vaccines,
                          ALVAC-HIV (vCP1452) and recombinant gp160
                          MN/LAI-2 with the novel adjuvant PCPP in
                          HIV-1 infected patients.
GENERAL DESCRIPTION       RATIONALE: HIV-infected patients treated with
                          antiretroviral therapy for prolonged periods
                          of time may show decreased levels of
                          HIV-specific immune responses. In these
                          patients, a prime-boost vaccine strategy may
                          induce both humoral and cell-mediated
                          immunity. The hypothesis of this study is
                          that the vaccine strategy selected will be
                          both safe and immunogenic in the patient
                          population being tested.
GENERAL DESCRIPTION       METHODOLOGY: Patients continue antiretroviral
                          medications throughout the course of this
                          study. All patients receive intramuscular
                          injections of ALVAC-HIV (vCP 1452) and
                          recombinant soluble gp160 MN/LAI-2 on Days 0,
                          30, 90, and 180. Patients are monitored for
                          safety 30 minutes after each immunization and
                          by telephone contact within 72 hours of each
                          vaccination. In addition, each patient
                          records adverse events in a diary. Patients
                          have regular physical exams, pregnancy tests,
                          and blood drawn for virologic and immunologic
                          assessments. The induction of HIV-specific
                          responses will be measured.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Immunology, Treatment IND.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 12 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 16/12 001024.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (980525)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: GCRC M01-RR00102.
                          U01AI41534-01. PMC/ADARC-001
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV infection. 2. Have absence of
                          multiply-spliced (MS) RNA determinations in
                          peripheral blood. 3. Have qualitative CD4
                          cell co-culture either negative or positive
                          for wild-type virus (as determined by
                          genotype) from blood. 4. Be participating in
                          ongoing clinical trials conducted by the
                          clinical arm of the Aaron Diamond AIDS
                          Research Center. 5. Have plasma HIV-RNA of
                          less than 50 copies/ml.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5.
PATIENT INCLUSION CRIT.   OTHER: Amylase <= 1.5 x ULN. ULN (Upper Limit
                          of Normal).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Abstinence or agree to use two
                          barrier methods of birth control /
                          contraception during the study.
PATIENT INCLUSION CRIT.   OTHER: Women and members of minority groups
                          will be actively recruited to ensure
                          representation and reflect disease patterns
                          in the local population.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: At least 2 years
                          of combination antiretroviral therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 19
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. HIV replication
                          in the presence of combination drug therapy
                          as evidenced by 1 of the following: plasma
                          HIV-RNA above the level of detection on 2
                          consecutive tests more than 2 weeks apart;
                          evidence of multiply-spliced (MS) HIV-RNA
                          species in peripheral blood (or tissue from
                          patients agreeing to optional biopsy or body
                          fluid specimen collection) or the presence of
                          culturable virus from blood (or tissue from
                          patients agreeing to optional biopsy or body
                          fluid specimen collection) that harbors
                          genotype consistent with drug resistance to 1
                          or more of the current antiretroviral agents
                          included in the patient's treatment regimen.
                          In specimens from optional tissue biopsy or
                          body fluid collection, there must be rare to
                          no HIV expressing cells as evidenced by in
                          situ hybridization. Additionally, there
                          should be no evidence of trapped virus in the
                          follicular dendritic cell network as seen by
                          in situ hybridization. 2. Allergy to eggs
                          and/or neomycin. 3. Evidence of cellular
                          immune responses to HIV-1 defined by fresh
                          CTL activity above 30 percent specific lysis
                          to 1 or more antigens at an
                          effector-to-target ratio of 25:1, or defined
                          by: CTLp above 1 in 100,000 to 1 or more
                          specific HIV antigens.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0317  gp160 MN/LAI-2
RESULTS                   Jin X, Ramanathan M Jr, Barsoum S, Deschenes
                          G, Ba L, Binley J, Hurley A, El Habib R,
                          Caudrelierl P, Zhang L, Ho DD, Markowitz M.
                          8th Conf Retro and Opportun Infect. 2001 Feb
                          4-8 (abstract no. 21).
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Administered on Days
                          0, 30, 90, 180: 1.0 ml. Drug 2: Administered
                          on Days 0, 30, 90, 180: 1.0 ml
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular, 10^7
                          TCID50. Drug 2: Intramuscular, 50 microg in
                          500 microg PCPP
OTHER TREATMENT INFO.     END POINT: Safety (monitoring for clinical
                          adverse events); and immunogenicity (baseline
                          and post-vaccination measurement of CTL
                          activity using bulk CTL assays, CTLp
                          frequencies, CTLe frequencies by tetramers if
                          available, proliferation to HIV specific
                          antigens in vitro, and levels of HIV specific
                          antibodies to gp120 and p24).
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Vaccine toxicity.
                          2. Patient decision. This decision will not
                          affect the ability to receive further care at
                          the Rockefeller University Hospital.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
NEW YORK                  Aaron Diamond AIDS Res Ctr 455 1st Ave New
                          York, NY 10016 Martin Markowitz [phone]
                          Recruiting 001115.

60
UNIQUE IDENTIFIER         NIH/01334
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-08-002
PROTOCOL TITLE            Evaluating Responses to Antiretroviral Drugs
                          in Cells and Tissues (The ERADICATE Study):
                          Comprehensive Comparisons of Viral and
                          Cellular Dynamics Among Previously-Untreated
                          Subjects with Acute HIV Infection
                          (Seroconversion Syndrome) or Recently
                          Acquired HIV Infection Versus the Early,
                          Middle, and Advanced Stages of Seropositive
                          HIV Infection.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: 1) To characterize, compare, and
                          contrast the decay curves for HIV RNA in
                          blood and other tissues in the setting of
                          acute HIV seroconversion and recently
                          acquired infection versus the early, middle,
                          and late stages of HIV infection in order to
                          assess the potential to achieve complete HIV
                          eradication from infected patients using
                          highly active antiretroviral therapy. 2) To
                          correlate serial quantitative HIV-1 RNA and
                          HIV-1 culture data obtained from blood with
                          concurrently obtained assays of other body
                          fluids and lymphoreticular tissues in order
                          to assess the viral burden in multiple body
                          compartments when very low or undetectable
                          plasma viral load has been achieved. 3) To
                          characterize the subtypes (T cells,
                          macrophages, others) and activation states
                          (by cell surface markers, local cytokine
                          production, etc.) of productively and
                          latently HIV-infected cells within
                          lymphoreticular and other body tissues during
                          the course of highly active therapy by
                          utilizing PCR-based and novel in situ
                          hybridization assays of biopsy materials. 4)
                          To describe the evolutionary dynamics of the
                          selection for resistant HIV subtypes within
                          several body compartments in acute versus
                          established HIV infection via serial
                          genotypic and phenotypic analyses of viral
                          isolates obtained before and during a course
                          of highly active combination therapy.
GENERAL DESCRIPTION       RATIONALE: Recent advancements in
                          antiretroviral therapy have led to a better
                          understanding of the natural history and
                          immunopathogenesis of HIV-1 infection. To
                          calculate the degree and duration of
                          antiretroviral effect necessary to eliminate
                          infection, characterization of residual
                          cellular and tissue HIV reservoirs following
                          high-level viral suppression is necessary.
                          The ERADICATE study will evaluate the
                          hypothesis that complete viral inhibition is
                          possible, regardless of HIV disease stage,
                          and leads to HIV eradication from tissues
                          over time.
GENERAL DESCRIPTION       METHODOLOGY: Patients are divided into 1 of 5
                          groups based on the stage of HIV infection.
                          Patients receive oral stavudine (d4T),
                          lamivudine (3TC), indinavir (IDV), and
                          nelfinavir (NFV) twice daily for 24 weeks.
                          All patients undergo basic blood sampling to
                          follow HIV-1 RNA levels and absolute T cell
                          subset numbers daily for 5 days; then 3 times
                          a week for 3 weeks; 2 times a week for 4
                          weeks; every 2 weeks for 12 weeks; and
                          monthly thereafter for a total of 3 years. In
                          addition, the following tissues are sampled
                          at baseline and after 2 weeks and 6 months on
                          therapy: 1) lymph node; 2) tonsillar; 3)
                          perirectal lymphoid; 4) cerebrospinal fluid;
                          5) and semen.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy,
                          Immunology, Clinical Evaluation, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 3 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 20/24 010731.
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (980529)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PHA 082
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have 1 of the following: 1. Plasma HIV RNA in
                          the absence of diagnostic HIV-1 ELISA or
                          Western blot with subsequent documentation of
                          HIV-1 seroconversion or repeated isolation of
                          HIV-1 in culture and no restrictions based on
                          CD4 count or viral load. 2. Current
                          diagnostic HIV-1 ELISA and Western blot with
                          documentation of negative HIV-1 serologic
                          tests within previous 120 days and no
                          restrictions based on CD4 count or viral
                          load. 3. Diagnostic HIV-1 serology with CD4
                          count greater than 500 cells/mm3 and lack of
                          evidence to demonstrate HIV acquisition
                          within previous 120 days. 4. Diagnostic HIV-1
                          serology with a CD4 count 50-500 cells/mm3.
                          5. Diagnostic HIV-1 serology with a CD4 count
                          of less than 50 cells/mm3.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.0 g/dl for men; > 8.5 g/dl
                          for women. Within 30 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 /microL Within 30
                          days prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Group 3: > 500
                          cells/mm3; Group 4: 50-500 cells/mm3; and
                          Group 5: < 50 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN (ULN) Upper Limit of
                          Normal.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN Within 30 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN Within 30 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: > 80 Within 30 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test within 14 days of study entry Abstinence
                          or effective method of birth control /
                          contraception including oral contraceptives
                          during the study.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Encouraged for
                          patients with advanced HIV disease:
                          Preventive and prophylactic therapy for
                          opportunistic infections.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Painful, bilateral peripheral sensitive
                          neuropathy which is irreversible or
                          chronically progressive.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          substance abuse that may compromise reliable
                          participation in the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy for more than 1 week. 2.
                          Immunomodulatory therapy within 2 weeks prior
                          to study entry including systemic
                          corticosteroids, cytokines, interleukins, and
                          interferon.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Medications contraindicated with indinavir
                          and/or nelfinavir (including triazolam,
                          midazolam, rifampin, terfenadine, astemizole,
                          and cisapride). 2. Immunomodulatory therapy
                          including systemic corticosteroids,
                          cytokines, interleukins, and interferon.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Severe
                          opportunistic infection or other systemic
                          illness which would limit the ability to
                          participate in this study. Moderately or
                          severely limiting symptoms such as marked
                          fatigue, anorexia, or dyspnea which would
                          make participation in this study difficult.
                          Patients in the advanced group may have a
                          history of disseminated infection such as MAC
                          or CMV as long as there is no evidence of
                          currently active infection (such as high
                          fevers or wasting) or significant sequelae of
                          involved organs (such as nephrotoxicity,
                          hepatotoxicity, or myelotoxicity failing to
                          meet laboratory inclusion criteria). 2.
                          Bleeding disorders that are clinically
                          significant, including hemophilia.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0043  Stavudine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 150 mg bid. Drug 2:
                          1000 mg bid. Drug 3: 1250 mg bid. Drug 4: 40
                          mg (30 mg if body weight is less than 60 kg)
                          bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 300 mg. Drug 2: 2000
                          mg. Drug 3: 2500 mg. Drug 4: 80 mg (60 mg if
                          body weight is less than 60 kg)
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Virologic response in blood and
                          other tissues among the groups.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Safety. 2.
                          Inability of the patient to adhere to study
                          requirements. 3. Drug toxicity. 4. If patient
                          fails to achieve less than 500 copies/ml
                          during the initial 24 weeks on the study
                          regimen, an alternative regimen, not provided
                          by the study, will be prescribed.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730

61
UNIQUE IDENTIFIER         NIH/01333
PROTOCOL ID NUMBERS       NIAID ACTG A5076
PROTOCOL TITLE            HIV-1 Resistance Testing During
                          Antiretroviral Failure: Comparison of
                          Sequencing Versus Phenotyping.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare time from randomization
                          to virologic failure between patients
                          assigned to sequencing (Arm A) versus those
                          assigned to phenotyping (Arm B).
GENERAL DESCRIPTION       RATIONALE: The emergence of drug resistance
                          is a major factor contributing to the failure
                          of antiretroviral therapy in HIV-infected
                          patients. Drug resistance can be detected by
                          genotypic or phenotypic assays, both having
                          distinct advantages and disadvantages.
                          Results from genotypic and phenotypic testing
                          are helpful in excluding from the subsequent
                          regimen drugs to which the resistance is
                          identified, and both tests predict virologic
                          response to salvage therapy in patients who
                          have failed a previous regimen. Resistance
                          testing is likely to be beneficial as an aid
                          in selecting a salvage regimen.
GENERAL DESCRIPTION       METHODOLOGY: At entry, patients are
                          randomized to Arm A (sequencing) or Arm B
                          (phenotyping) and have a resistance test
                          drawn while still receiving the current
                          regimen even though regimen failure is
                          suspected. The test results are available
                          between Weeks 1 and 4, inclusive. There are
                          weekly visits for the first 4 weeks after
                          entry to monitor viral load and maintenance
                          of the current failing (prestudy) regimen. If
                          virologic failure is confirmed, a new regimen
                          is chosen and prescribed at the first visit
                          after resistance test results are available.
                          [AS PER AMENDMENT 12/6/00: If the resistance
                          assay fails to yield results, another regimen
                          is chosen and prescribed based on the
                          patient's medical and medication history.] If
                          virologic failure is not confirmed, the
                          current drug regimen is not changed.
                          Otherwise, on-site study visits occur every 4
                          weeks until Week 24 and then every 8 weeks
                          thereafter through Week 48. [AS PER AMENDMENT
                          12/6/00: on-site study visits occur every 4
                          weeks until Week 24 and then every 8 weeks
                          thereafter]. Medical resource use is assessed
                          at baseline and then every 8 weeks through
                          Week 48. Quality of life is assessed at
                          baseline and then every 16 weeks through Week
                          48.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Questionnaire, Clinical Evaluation, Viral
                          load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 600 patients. Maximum
                          enrollment at each site will be 18 patients
                          per site (32 total sites). At a point 4
                          months or later after enrollment begins, to b
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until last
                          enrolled patient reaches Week 48.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 51/600 010731.
PROTOCOL DETAILS          STUDY DURATION: 26 weeks accrual plus 48
                          weeks treatment.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 47
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (001206)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5076
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2. Have plasma
                          HIV-1 RNA level within 30 days of study entry
                          confirming virologic failure as follows: 1
                          result greater than or equal to 10,000
                          copies/ml; or 2 results greater than or equal
                          to 1,000 copies/ml and less than 10,000
                          copies/ml (if only 1 result available at the
                          screening is greater than or equal to 1,000
                          copies/ml but less than 10,000 copies/ml, a
                          confirmatory HIV-1 RNA measure greater than
                          or equal to 1,000 copies/ml is required). 3.
                          Currently be virologically failing their
                          second, third, or fourth antiretroviral
                          regimen which includes 3 or more drugs in
                          combination. Virologic failure is defined
                          based on viral load criteria in the protocol.
                          4. Have written consent of a parent or
                          guardian if less than 18 years old.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable current 3
                          or more drug combination antiretroviral
                          regimen for at least 8 weeks before study
                          entry. Allowed: 1. Brief use of
                          corticosteroids for Pneumocystis pneumonia or
                          asthma. 2. Hydroxyurea or adefovir, including
                          at a time when they were investigational. 3.
                          Antiretrovirals that are tested in the
                          phenotypic assay including zidovudine,
                          lamivudine, stavudine, abacavir, didanosine,
                          zalcitabine, nevirapine, efavirenz,
                          delaviridine, ritonavir, saquinavir,
                          indinavir, nelfinavir, amprenavir,
                          lopinavir/ritonavir.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. Brief use
                          of corticosteroids for Pneumocystis pneumonia
                          or asthma. 2. Topical and oral antifungal
                          agents. 3. Treatment, maintenance, or
                          chemoprophylaxis with approved agents for
                          opportunistic infections as clinically
                          indicated (unless excluded elsewhere in the
                          protocol). 4. Antibiotics as clinically
                          indicated (unless excluded elsewhere in the
                          protocol). 5. Hydroxyurea. 6. Use of
                          zidovudine, lamivudine, stavudine, abacavir,
                          didanosine, zalcitabine, nevirapine,
                          efavirenz, delaviridine, ritonavir,
                          saquinavir, indinavir, nelfinavir,
                          amprenavir, lopinavir/ritonavir.
                          Lopinavir/ritonavir can be used if
                          appropriate based on resistance test results
                          and if the patient qualifies for access to
                          them (e.g., through compassionate use or
                          expanded access programs from the drug
                          manufacturer). [7. AS PER AMENDMENT 12/6/00:
                          Colony-stimulating factors for neutropenia
                          and/or anemia.].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 14
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Genotypic or phenotypic resistance test
                          results reported to the patient or his/her
                          clinician. 2. Intestinal malabsorption. 3.
                          Failure of only 1 combination antiretroviral
                          regimen. 4. Failure of 5 or more
                          antiretroviral treatment regimens, including
                          the currently failing regimen, with each
                          failing regimen containing at least 3, but no
                          more than 5, drugs, as defined in the
                          protocol. 5. Failure of antiretroviral
                          therapy caused by nonadherence to medication.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Mega-HAART
                          therapy regimen, defined as a 6 or more drug
                          combination antiretroviral regimen.
                          Hydroxyurea is not counted as an
                          antiretroviral agent for this purpose. 2. HIV
                          vaccines, immunomodulators (brief use of
                          corticosteroids for Pneumocystis pneumonia or
                          asthma is allowed), or investigational drugs
                          at any time prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral therapies other than those
                          allowed under Inclusion-Concurrent
                          Medications. 2. HIV vaccines. 3.
                          Immunomodulators [AS PER AMENDMENT 12/6/00:
                          other than those allowed under
                          Inclusion-Concurrent Medications]. 4.
                          Investigational drugs. 5. Contraindicated for
                          patients taking protease inhibitors:
                          Contraindicated medications including
                          amiodarone, cholestyramine, ergot alkaloids
                          or drugs containing derivatives of ergot
                          alkaloids, ganciclovir, interferon-alpha,
                          midazolam, quinidine, ribavirin, rifampin,
                          sucralfate, [AS PER AMENDMENT 12/6/00:
                          flecainide, pimozide, and propafenone,] and
                          terfenadine.
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Time from randomization until
                          virologic failure, with virologic failure
                          defined by: 1) lack of initial response; 2)
                          early rebound; or 3) loss of suppression, for
                          viral loads and times defined in the
                          protocol.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Failure to attend 3
                          consecutive study visits. 2. Investigator's
                          decision. 3. Protocol team or NIAID's
                          decision.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 010528.
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010117.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 001129.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010228.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010323.
CALIFORNIA                San Francisco VA Med Ctr 3180 18th St San
                          Francisco, CA 941104206 Julieann Lewis
                          [phone] Recruiting 010117.
CALIFORNIA                Santa Clara Valley Med Ctr / AIDS Community
                          Rsch Consortium 751 South Bascom Ave San
                          Jose, CA 951282699 Debbie Slamowitz
                          [phone] Recruiting 010119.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 001129.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Mario Guerrerro
                          [phone] Recruiting 010522.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 001129.
COLORADO                  Denver Dept of Health and Hosps 4200 East 9th
                          Ave / Campus Box B-196 Denver, CO 80262 M
                          Graham Ray [phone] Recruiting 010117.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010117.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010205.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Ericka Patrick [phone] Recruiting
                          010406.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010119.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 010119.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010228.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010410.
MASSACHUSETTS             Brigham and Women's Hosp Div of Infectious
                          Diseases / 15 Francis St PBB A-4 Boston, MA
                          02215 Carolyn Koziol [phone] Recruiting
                          010222.
MASSACHUSETTS             Harvard (Massachusetts Gen Hosp) 55 Fruit St
                          / Founders Bldg 8th Floor Boston, MA 02114
                          Teri Flynn [phone] Recruiting 010222.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 010213.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Charles Raines
                          [phone] Recruiting 010723.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010522.
NORTH CAROLINA            Moses H Cone Memorial Hosp 1200 North Elm St
                          Greensboro, NC 27401 Lisa Dasnoit
                          [phone] Recruiting 010405.
NORTH CAROLINA            Carolinas Med Ctr PO Box 32861 Charlotte, NC
                          28232 Sharon Hewat [phone] Recruiting
                          010228.
NORTH CAROLINA            Carolinas Med Ctr 1000 Blythe Blvd / MEB 202
                          Charlotte, NC 28203 Marjorie Massey
                          [phone] Recruiting 010119.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 010117.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010406.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 010119.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Rachele Cruz
                          [phone] Recruiting 010323.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] Recruiting 010119.
NEW YORK                  Cornell Clinical Trials Unit 119 West 24th St
                          / Ground Floor New York, NY 10011 Todd
                          Stroberg [phone] Recruiting 010222.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 010213.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Valery Hughes [phone]
                          Recruiting 010213.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010405.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010318.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 010316.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 010205.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 010405.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] Recruiting 010730.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010115.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 010405.
RHODE ISLAND              Brown Univ / Miriam Hosp 164 Summit Ave /
                          Immunology Ctr Providence, RI 02906 Joan
                          Gormley [phone] Recruiting 010405.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 010222.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 010612.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 010119.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010323.

62
UNIQUE IDENTIFIER         NIH/01331
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-08-003
PROTOCOL TITLE            Quantitative Assessment of Viral and
                          Lymphocyte Dynamics in Blood and
                          Lymphoreticular Tissues of HIV-1 Infected
                          Patients Treated with Antiretroviral Agents.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To obtain a comprehensive molecular
                          assessment of HIV-1 load and expression in
                          blood and secondary lymphoid organs,
                          including lymph node, tonsil, and gut. To
                          evaluate the kinetics of turnover of each
                          viral component following the initiation of
                          antiretroviral therapy as a means to
                          determine the respective lifespans
                          (half-lives) of virus and of different viral
                          RNA and DNA species. To evaluate the response
                          of CD4+, CD8, and other lymphocyte
                          populations to antiretroviral therapy. To
                          develop a mathematical model of virus-host
                          interaction based on accurate measurements of
                          HIV-1 and CD4+ lymphocyte dynamics.
GENERAL DESCRIPTION       RATIONALE: The natural history and
                          pathogenesis of HIV-1 infection are linked
                          closely to the replication of virus in the
                          body. Studies obtained entirely from analyses
                          of peripheral blood led to a shift in the
                          understanding of HIV-1 pathogenesis. Recent
                          studies have shown that lymphoid tissues are
                          a major reservoir for HIV and the primary
                          site of virus replication. The proposed
                          studies will provide the first comprehensive
                          assessment of HIV-1 expression and lymphocyte
                          response in both blood and lymphocyte tissue
                          compartments. The data obtained will provide
                          new insight into HIV-1 pathogenesis and
                          provide a more rational basis for treatment
                          decisions concerning early therapy of HIV-1
                          infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients are admitted to the
                          hospital for insertion of an angiocath to
                          collect blood samples periodically over 48
                          hours on the day study medication from the
                          parent study is initiated. After discharge,
                          additional blood samples are obtained over a
                          6-month period. Within 7 days prior to a
                          scheduled biopsy, patients have physical
                          examinations and laboratory evaluations done.
                          All patients undergo some combination of the
                          following during the 2-week prestudy
                          evaluation period and at Weeks 4 and 24: a)
                          superficial lymph node biopsy from cervical,
                          axillary, or inguinal area; b) rectal biopsy;
                          and/or c) tonsillar biopsy. The tissue
                          samples provide an assessment of viral and
                          cellular dynamics.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Immunology, Clinical
                          Evaluation, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 6 months (2
                          weeks pre-study evaluation plus 24 weeks
                          on-study).
PROTOCOL DETAILS          ACTUAL ACCRUAL: 2/60 010731.
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: R01 AI35467.
                          UAB/PHA100R
PROTOCOL DETAILS          STUDY DESIGN: Cohort Study
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: Be
                          participants in other University of Alabama
                          Internal Review Board (IRB)-approved studies.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 80000 /mm3 Within 7 days
                          of study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   OTHER: PTT within normal limits. Within 7
                          days of study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Chronic
                          therapy for an active AIDS-defining
                          opportunistic infection, other than
                          prophylactic therapies.
OTHER TREATMENT INFO.     END POINT: HIV burden and replication in
                          peripheral blood and lymphoid tissue.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may withdraw from the
                          study for any reason at any time.
OTHER TREATMENT INFO.     MODIFICATION: Doses of parent study drugs may
                          be modified as a result of suspected
                          drug-related toxicity.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730

63
UNIQUE IDENTIFIER         NIH/01330
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-01-001
PROTOCOL TITLE            A Single Center, Randomized Open Label Study
                          of Initial Interleukin-2 Compared to Delayed
                          Interleukin-2 When Added to Zidovudine, 3TC
                          and Nelfinavir In Order to Modulate Immune
                          Function and to Sustain Suppression of HIV-1
                          Replication Among Those Persons with Primary
                          or Early HIV Infection.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To evaluate dynamics of HIV in
                          different tissue compartments of maximally
                          suppressive antiretroviral medications with
                          interleukin-2 (IL-2) influences on viral
                          pathogenesis and immune responses to HIV
                          infection. To determine the patterns of
                          immunologic activation as measured by cell
                          surface marker levels and soluble and
                          cell-associated cytokines when persons with
                          acute or early HIV infection are treated with
                          antiretrovirals and IL-2. To examine whether
                          the extent of CD8+ cell anti-viral activity
                          as measured by non-cytotoxic and cytotoxic
                          responses affects the kinetics of viral
                          replication and viral load in various tissue
                          compartments. To determine whether a broad
                          cellular immune response to HIV infection,
                          measured by T cell repertoire, cytotoxic T
                          cell lymphocyte function, and CD4 T helper
                          function, correlates with the patterns of
                          cellular immune anti-viral responses among
                          persons with acute and early HIV infection
                          treated with antiretrovirals and IL-2.
GENERAL DESCRIPTION       RATIONALE: Following initial exposure to HIV,
                          infection is established through the rapid
                          replication of a homogeneous strain of the
                          virus. Preliminary studies of combination
                          antiretroviral therapy show that it is
                          possible to reduce circulating HIV RNA to
                          below detectable levels at this phase.
                          Sustained suppression of viral replication or
                          viral eradication may be possible only before
                          HIV has become integrated in the immune
                          system and undergone a number of quasi
                          species mutations. This study will assess the
                          feasibility of interrupting the natural
                          course of HIV infection by using
                          antiretroviral therapy soon after initial
                          infection.
GENERAL DESCRIPTION       METHODOLOGY: Nelfinavir (NFV) and
                          zidovudine/lamivudine (Combivir) treatment
                          starts as soon as possible and at most, 7
                          days from the diagnosis of HIV infection, and
                          continues for 104 weeks. After 4 weeks of
                          therapy patients are randomized to begin
                          receiving IL-2 therapy or to delay starting
                          it until Week 48. Patients may choose not to
                          receive IL-2 treatment and remain in the
                          study. Patients have clinic visits to measure
                          viral load every 4 weeks. At a final clinic
                          visit, physical examinations and collection
                          of semen, cervical fluid, blood, and saliva
                          specimens are done. Eligible consenting
                          patients have a tonsil biopsy. Patients are
                          reimbursed for participation in this study.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (001002)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 120 patients. Recruited
                          from the AIDS Clinic, San Francisco General
                          Hospital (SFGH), or by self-referral or
                          physician referral.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 224/120 010731.
PROTOCOL DETAILS          STUDY DURATION: 3 years recruitment plus 2
                          years treatment duration.
PROTOCOL DETAILS          VERSION NUMBER & DATE: (980311)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have recent HIV infection confirmed by either
                          viral RNA with no detectable HIV antibody,
                          documentation of seroconversion in the past 6
                          months, or an unreactive detuned antibody (OD
                          of less than 0.75) with a positive ELISA. 2.
                          Be available for follow-up for a period of at
                          least 96 weeks.
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 27 % In the absence of blood
                          transfusions or erythropoietin treatment in
                          the preceding 2 weeks. Within 28 days of
                          study treatment.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl (males) or 8.8 g/dl
                          (females). Within 28 days prior to study
                          treatment.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 Within 28 days
                          prior to study treatment.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN Within 28 days prior
                          to study treatment.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 10 x ULN Within 28 days prior
                          to study treatment.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN ULN (Upper Limit of
                          Normal). Within 28 days prior to study
                          treatment.
PATIENT INCLUSION CRIT.   OTHER: WBC >= 2,000/mm3. Within 28 days prior
                          to study treatment.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study Negative
                          pregnancy test within 3 days of initial drug
                          administration.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: All approved
                          medications.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Documentation of other cause for baseline
                          laboratory values (e.g., Epstein-Barr virus,
                          CMV mononucleosis syndrome, or acute
                          streptococcal pharyngitis). 2. Chronic
                          diarrhea (4 to 10 stools per day of 30 days
                          or longer duration). 3. Neoplastic disease
                          requiring systemic cytotoxic or radiation
                          therapy within 1 month of baseline/Day 0 and
                          without complete recovery from the effects of
                          these therapies.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active substance
                          abusers whose abuse interferes with the
                          ability to comply with study requirements.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 1 month of baseline/Day 0 and patient
                          has not completely recovered from the effects
                          of this therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy beyond 4 weeks. 2. Systemic cytotoxic
                          therapy within 1 month of baseline/Day 0 and
                          patient has not completely recovered from the
                          effects of this therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Neoplastic
                          disease requiring systemic cytotoxic or
                          radiation therapy or patients who have had
                          these therapies within 1 month of
                          baseline/Day 0 and have not completely
                          recovered from the effects of these
                          therapies. 2. Unstable or severe intercurrent
                          medical conditions. 3. Clinically significant
                          malabsorption syndrome, i.e., chronic
                          diarrhea (4 to 10 stools per day of 30 days
                          or longer duration), sprue, Whipple's
                          disease, pancreatic disease, irritable bowel
                          syndrome, Crohn's disease, ulcerative
                          colitis, or amyloidosis.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0285  Lamivudine/Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 300 mg
                          zidovudine/150 mg lamivudine q12h. Drug 2:
                          1250 mg q12h. Drug 3: 7.5 million units bid
                          for 5 days, every 8 weeks
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 600 mg zidovudine/300
                          mg lamivudine. Drug 2: 2500 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 300 mg
                          zidovudine/150 mg lamivudine. Drug 2: Oral.
                          Drug 3: Injection
OTHER TREATMENT INFO.     TREATMENT DURATION: 104 weeks (patients must
                          complete at least 96 weeks of therapy).
OTHER TREATMENT INFO.     END POINT: The proportion of patients with no
                          evidence of infectious virus; the incidence
                          of adverse events.
OTHER TREATMENT INFO.     MODIFICATION: If a patient experiences a
                          dose-limiting adverse event, the patient will
                          be managed as medically appropriate and
                          dosing will be held until the dose-limiting
                          toxicity has decreased in severity at least 2
                          grades and is no longer considered
                          dose-limiting. Dosing may be reinstated at
                          the next-lower dose level on the
                          every-8-hours dosing schedule. The maximum
                          duration of dosing will be 5 days and will
                          not be extended for doses missed due to
                          toxicity. Patients who develop intolerance to
                          AZT may use stavudine (d4T).
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20001002

64
UNIQUE IDENTIFIER         NIH/01328
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-04-008
PROTOCOL TITLE            An Open-Label, Single Center Trial to
                          Evaluate the Efficacy and Safety of Quadruple
                          Chemotherapy (Zidovudine, EPIVIR, 1592U89,
                          and 141W94) in Subjects Infected with HIV-1
                          (GW QUAD).
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: 1. To determine the safety and
                          efficacy of combination chemotherapy in HIV-1
                          infected patients using 141W94 (amprenavir
                          [APV]) and 1592U89 (abacavir [ABC]) in
                          combination with zidovudine (ZDV)/ lamivudine
                          (3TC). 2. To determine the dynamics of HIV-1
                          in gut-associated lymphoid tissue in the
                          gastrointestinal tract. a. To compare viral
                          activity in the lymph tissue of the
                          gastrointestinal tract to that of plasma. b.
                          To determine the rate of decay of HIV-1 in
                          tissue. 3. To determine the change in
                          lymphocyte subpopulations in blood and
                          gastrointestinal lymphoid tissue in patients
                          treated with combination antiretroviral
                          therapy (ART). 4. To monitor the decay of
                          HIV-1 in cerebrospinal fluid (CSF) in
                          patients who have detectable HIV-1 in CSF at
                          baseline.
GENERAL DESCRIPTION       RATIONALE: With effective combination ART,
                          there is a decrease in HIV-1 RNA in plasma
                          after 2 to 3 weeks. A second, slower phase of
                          viral decay is thought to occur in long-lived
                          macrophages, with a minimal contribution from
                          lymphocytes. This study addresses whether
                          there is a third reservoir such as the
                          central nervous system. Additionally, the
                          study aims to provide a better understanding
                          of the type and length of ART required to
                          suppress HIV-1 replication in multiple
                          reservoirs.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive treatment with
                          ZDV, 3TC, ABC, and APV daily for 24 weeks.
                          Clinic visits occur weekly until Week 4, then
                          every 2 weeks until Week 12, then monthly.
                          Blood and urine samples are collected and
                          patients are monitored for clinical or
                          laboratory abnormalities. Laboratory tests to
                          assess side effects and virologic and
                          immunologic parameters, including viral
                          quantification of CSF on all chronically
                          infected patients and selected consenting
                          acutely infected patients, are determined. In
                          a pharmacoeconomic component of this study,
                          patients have interviews and complete
                          questionnaires at 5 clinic visits.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (001002)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety, Questionnaire, Viral
                          load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 25 patients. Approximately
                          25 evaluable patients: 12 acutely infected
                          and 13 chronically infected.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks, with
                          extension to 48 weeks or indefinitely, based
                          on sponsor and FDA agreement, with IRB
                          approval.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 29/25 001018.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: 4 (970826)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PROA2003
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have a chronic HIV-1 infection (more than 90
                          days) as defined by positive ELISA and
                          Western blot; or are acutely infected with
                          HIV-1 as defined by detectable viral activity
                          with a positive plasma HIV-1 RNA by bDNA and
                          1 of the following: absent HIV-1 antibody by
                          ELISA, positive ELISA and an evolving Western
                          blot (minimum 2 bands), or clinical history
                          consistent with HIV-1 infection within 90
                          days and a documented negative HIV-1 test
                          within 120 days of screening. 2. Have a viral
                          load by bDNA of at least 5,000 copies/ml of
                          plasma (for chronically infected patients
                          only). 3. Have ability to comply with the
                          investigational nature of the study.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 80000 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2 x ULN For chronically
                          infected patients. Any abnormalities of liver
                          function th
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2 x ULN For chronically
                          infected patients. Any abnormalities of liver
                          function thought not to be due to acute HIV-1
                          infection for acutely infected patients are
                          excluded.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test within 7
                          days of study entry Abstinence or effective
                          method of birth control / contraception 1
                          month before and during the study.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Encouraged:
                          Chemoprophylaxis for HIV-associated
                          conditions, if appropriate, at the discretion
                          of the patient and his/her physician.
                          Allowed: GM-CSF, G-CSF, or erythropoietin for
                          hematologic supportive therapy. Allowed with
                          caution: 1. Agents that inhibit cytosolic
                          alcohol dehydrogenase including ethanol,
                          disulfiram, chlorzoxazone, chlorpromazine,
                          isoniazid, and chloral hydrate. 2. Drugs
                          known to cause liver toxicity or induce
                          myelosuppression. 3. Drugs known to effect
                          renal tubular secretion (such as probenecid
                          or cimetidine). Careful monitoring should be
                          used. 4. Drugs which may interact at CYP3A4
                          (either a substrate, inhibitor, or inducer of
                          the enzyme) including, but not limited to,
                          alprazolam, carbamazepine, codeine,
                          clarithromycin, dapsone, diazepam, diltiazem,
                          erythromycin, estrogens, fluvastatin,
                          glucocorticoids, imipramine, itraconazole,
                          ketoconazole, lidocaine, lovastatin,
                          nifedipine, phenobarbital, phenytoin,
                          quinidine, rifabutin, rifampin, simvastatin,
                          and warfarin. 5. Drugs with known high
                          protein-binding properties.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Coagulopathy. 2. High risk for developing
                          endocarditis (history of endocarditis,
                          rheumatic heart disease, or heart valve
                          prostheses). 3. Inflammatory bowel disease or
                          malignancy, intestinal ischemia,
                          malabsorption, or other gastrointestinal
                          dysfunction which might interfere with drug
                          absorption or render the patient unable to
                          take oral medication. 4. Unexplained fever
                          greater than 38.5 C for more than 14 days
                          within 30 days of enrollment.
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Institutionalized or
                          mentally disabled patients or prisoners.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy (with the exception of local Kaposi's
                          sarcoma treatment).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Protease
                          inhibitors or 3TC. 2. For acutely infected
                          patients, antiretroviral therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Immunomodulating agents such as systemic
                          corticosteroids, interleukins, thalidomide,
                          anti-cytokine agents or interferons,
                          cytotoxic chemotherapeutic agents, and
                          antioxidants. 2. Terfenadine, astemizole,
                          cisapride, triazolam, midazolam, and
                          ergotamine/dihydroergotamine containing
                          regimens or other medications metabolized by
                          the cytochrome P450 enzyme systems. 3.
                          Experimental agents or antiretroviral drugs
                          other than study drugs. 4. Drugs which
                          potentiate ZDV toxicity, i.e., those causing
                          anemia or neutropenia, or undergoing
                          significant glucuronidation. 5. Vitamin E
                          supplements.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1.
                          Institutionalized, mentally disabled, or
                          imprisoned. 2. Critically ill. 3. Active
                          opportunistic infection requiring acute
                          therapy (therapy must be completed 30 days
                          before the start of the study). 4. Inability
                          to comply with the protocol requirements, as
                          judged by the investigator, for reasons other
                          than those specified. 5. Transfusion
                          dependency.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0258  Amprenavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 300 mg bid. Drug 2:
                          150 mg bid. Drug 3: 300 mg bid. Drug 4: 1200
                          mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 300 mg.
                          Drug 3: 600 mg. Drug 4: 2400 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 300-mg tablets.
                          Drug 2: Oral, 150-mg tablets. Drug 3: Oral,
                          100-mg caplets or 300-mg tablets. Drug 4:
                          Oral, 150- or 200-mg soft gel caps
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks, with extension
                          to 48 weeks or indefinitely, based on sponsor
                          and FDA agreement, with IRB approval.
OTHER TREATMENT INFO.     DISCONTINUE: Patients must be discontinued
                          for the following reasons: 1. Virologic
                          failure or a greater than 50 per cent
                          increase in plasma viremia from baseline on 2
                          separate occasions within 30 days and after
                          completion of at least 4 weeks of therapy. 2.
                          An adverse event which requires
                          discontinuation of study drugs. 3.
                          Requirement for systemic chemotherapy or
                          radiation therapy for a malignancy (with the
                          exception of local treatment for Kaposi's
                          sarcoma). 4. Pregnancy. 5. Withdrawal-grade
                          toxicity. 6. Lost to follow-up or
                          non-compliant with clinic appointments (in
                          the opinion of the investigator). 7. Choice
                          of patient to withdraw without prejudice to
                          their medical care. 8. Investigator's
                          discretion to withdraw a patient. Patients
                          dropping out of the study due to an adverse
                          event are followed until the adverse event
                          has resolved, become clinically insignificant
                          or stabilized, or patients are lost to
                          follow-up.
OTHER TREATMENT INFO.     MODIFICATION: Dosage may be altered in the
                          event of toxicity.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20001002
NEW YORK                  Aaron Diamond AIDS Res Ctr 455 1st Ave New
                          York, NY 10016 Martin Markowitz [phone]
                          Recruiting 001002.

65
UNIQUE IDENTIFIER         NIH/01326
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-08-004
PROTOCOL TITLE            Evaluation of Subjects with Primary or Early
                          Human Immunodeficiency Virus (HIV) Infection.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To assess if potent antiretroviral
                          therapy early in the course of HIV infection
                          can lead to the absence of detectable viral
                          replication in the plasma and tissues. To
                          compare the absence of detectable viral
                          replication in the plasma and tissues by
                          standard RNA PCR (less than 200 copies/ml)
                          and culture techniques versus by
                          ultrasensitive RNA-PCR (less than 20
                          copies/ml) and culture techniques while on
                          potent therapy. To assess the clearance of
                          proviral DNA during potent antiretroviral
                          therapy early in the course of HIV infection
                          and whether the presence of proviral DNA will
                          lead to detectable RNA levels following the
                          discontinuation of potent antiretroviral
                          therapy.
GENERAL DESCRIPTION       RATIONALE: Primary and early HIV infection
                          represents a potentially unique opportunity
                          to better understand the pathogenesis of HIV
                          infection, as well as to potentially prevent
                          the establishment of latent infection.
                          Approved antiretroviral therapy is able to
                          reduce plasma viremia to unmeasurable levels
                          in established infection and several groups
                          have observed comparable effects in recently
                          infected adults. This study is designed to
                          evaluate and follow a cohort of patients with
                          primary or early HIV infection and to
                          evaluate the time course of latent infection
                          and whether latent infection in CD4 cells
                          will allow viral persistence despite
                          antiretroviral therapy.
GENERAL DESCRIPTION       METHODOLOGY: Patients begin antiretroviral
                          therapy within 7 days of enrollment. All
                          patients are evaluated for treatment
                          compliance and complete a compliance
                          questionnaire regularly. Clinical
                          evaluations, including CD4, CD8, and HIV RNA
                          counts also are done regularly.
                          Antiretroviral therapy is discontinued if
                          there is no detectable virus by
                          ultrasensitive assay and culture techniques
                          in plasma, PBMCs, and lymphoid tissue. In a
                          subset of patients, genital secretions and
                          CSF (cerebrospinal fluid) are evaluated. If
                          relapse occurs, antiretroviral therapy is
                          re-instituted. In addition, virology and
                          immunology substudies are performed.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug therapy,
                          Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 45-60 patients. Enrollment
                          is planned to be completed in approximately 3
                          to 4 years.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 36 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 4/45-60 001018.
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (971028)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: ACRU 010
PROTOCOL DETAILS          STUDY DESIGN: Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have 1 of the following: 1. Acute HIV-1
                          infection: detectable HIV activity with a
                          positive plasma HIV-1 DNA or a positive
                          plasma HIV-1 RNA (greater than 2000
                          copies/ml) within 4 days prior to study
                          entry, performed by a certified ACTG Virology
                          Laboratory, and 1 of the following: negative
                          or indeterminate ELISA; positive ELISA and
                          evolving Western blot (minimum of 2 bands);
                          clinical history consistent with HIV-1
                          infection within 90 days and a documented
                          negative HIV-1 test within 120 days of
                          screening. 2. Recent seroconversion: positive
                          ELISA and Western blot within 6 months of
                          negative test. 3. Early infection: positive
                          ELISA and Western blot within 6 to 12 months
                          of a negative test.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 10 g/dl for men and > 9 g/dl
                          for women, within 14 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 /mm3 Within 14 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): < 2 x ULN Within 14 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 2 x ULN Within 14 days prior to
                          study entry. ULN (Upper Limit of Normal).
PATIENT INCLUSION CRIT.   KARNOFSKY: = 80 Within 14 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception during the study and for 90
                          days after Not breast-feeding Negative
                          pregnancy test within 14 days of study entry
                          Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Alternative
                          therapies such as vitamins, acupuncture, and
                          visualization techniques. Patients should
                          report the use of these therapies;
                          alternative therapies will be recorded but
                          not keyed.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required:
                          Chemoprophylaxis for Pneumocystis carinii
                          pneumonia for all patients who have a CD4
                          cell count less than 200 cells/mm3. Allowed:
                          1. Treatment, maintenance, or
                          chemoprophylaxis with approved agents for
                          opportunistic infections as clinically
                          indicated (unless specifically excluded in
                          the protocol). 2. All antibiotics as
                          clinically indicated (unless specifically
                          excluded in the protocol). 3. Systemic
                          corticosteroid use for less than 21 days for
                          acute problems as medically indicated.
                          Chronic systemic corticosteroid use is not
                          permitted unless it is within physiological
                          replacement levels. 4. Recombinant
                          erythropoietin (rEPO) and granulocyte
                          colony-stimulating factor (G-CSF, filgrastim)
                          as medically indicated. 5. Regularly
                          prescribed medications such as antipyretics,
                          analgesics, allergy medications,
                          antidepressants, sleep medications, oral
                          contraceptives, megestrol acetate,
                          testosterone, or any other medications as
                          medically indicated (unless specifically
                          excluded in the protocol).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation within
                          30 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Chronic
                          systemic corticosteroid use, unless it is
                          within physiological replacement levels.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy. 2. Erythropoietin, G-CSF, or GM-CSF
                          within 30 days prior to study entry. 3.
                          Interferons, interleukins, cytotoxic
                          chemotherapy, or HIV vaccines within 30 days
                          prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Those
                          medications which would be contraindicated
                          with medications prescribed. Avoided: Herbal
                          medications. Patients should report the use
                          of these therapies; alternative therapies
                          will be recorded but not keyed.
OTHER TREATMENT INFO.     END POINT: Determine the proportion of
                          patients who achieve viral suppression
                          (RNA-PCR less than 200 copies/ml) and culture
                          negativity by standard assay; determine the
                          proportion of patients who achieve viral
                          suppression (Ultrasensitive assay less than
                          20 copies/ml) and culture negativity by
                          ultrasensitive culture technique; assess the
                          correlation between viral load in lymphoid
                          tissue, CSF, genital secretions and plasma
                          and PBMC in a subset of patients; assess the
                          correlation between baseline virologic and
                          immunologic markers and virologic response;
                          assess the incidence of viral strains showing
                          mutations known to be associated with
                          therapy, which will be done in all 5
                          compartments studied (plasma, PBMC, lymph
                          nodes, CSF, and genital secretions) in a
                          subset of patients; characterize the
                          occurrence of phenotypic and genotypic
                          resistance to therapy in patients who develop
                          virologic relapse; evaluate the virologic
                          response and baseline genotype of virus in
                          patients based on the treatment history of
                          known partners.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patients miss
                          consecutive clinic visits, as determined by
                          the investigator. 2. Patients withdraw from
                          the study at any time for any reason. 3. The
                          investigator removes patients from the study
                          for clinical reasons which he/she believes
                          are life-threatening to the patient.
OTHER TREATMENT INFO.     MODIFICATION: Patients who require a dose
                          modification are re-evaluated on a weekly
                          basis.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730

66
UNIQUE IDENTIFIER         NIH/01325
PROTOCOL ID NUMBERS       NIAID ACTG A5087
PROTOCOL TITLE            A Prospective, Multicenter, Randomized Trial
                          Comparing the Efficacy and Safety of
                          Fenofibrate Versus Pravastatin in
                          HIV-Infected Subjects with Lipid
                          Abnormalities.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine whether fenofibrate and
                          pravastatin are equivalent (with respect to
                          clinical response) in the treatment of
                          HIV-related hyperlipidemia at Week 12. To
                          compare the safety (with respect to changes
                          in laboratory parameters and the occurrence
                          of adverse events) of fenofibrate versus
                          pravastatin in the treatment of HIV-related
                          hyperlipidemia at Week 12.
GENERAL DESCRIPTION       RATIONALE: Lipid disorders associated with
                          HIV infection and antiretroviral therapy are
                          of growing concern. There is little
                          information available on the safety and
                          efficacy of statins or fibrates in the
                          treatment of HIV-associated hyperlipidemias.
                          Fenofibrate and pravastatin both are able to
                          reduce low-density lipoproteins (LDL) and
                          triglycerides (TG), but it is unclear whether
                          one therapy will be more effective than the
                          other, or if combination therapy will be
                          needed to achieve desirable reductions in
                          both LDL and TG.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          either Arm A or Arm B and stratified by
                          gender, TG level, and number of
                          cardiovascular risk factors. Patients add
                          daily fenofibrate (Arm A) or pravastatin (Arm
                          B) to their antiretroviral therapy for 48
                          weeks. Evaluations at Week 12 determine LDL,
                          TG, and high-density lipid (HDL) levels.
                          Patients who achieve clinical goals for these
                          levels stay on the drug for the rest of the
                          study. Patients who do not achieve the goals
                          by Week 12 receive a combination of
                          pravastatin and fenofibrate for the rest of
                          the study. At regular clinic visits, patients
                          have physical exams and are questioned about
                          their medications, diet, and exercise. Blood
                          samples are drawn for clinical evaluations,
                          including lipid profiles and HIV-1 RNA
                          monitoring.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy, Drug
                          safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 630 patients. 315 are
                          enrolled in each of 2 arms.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 174/630 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 58
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010418)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5087
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2. Be on a
                          lipid-lowering diet and have exercised for at
                          least 30 days prior to screening, per patient
                          report. Patients will be asked whether they
                          had counseling from a health care provider,
                          but no substantiating reports will be
                          required. [AS PER AMENDMENT 4/18/01: The
                          lipid-lowering diet and exercise program do
                          not have to be physician-prescribed.].
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.1 g/dl for men and > 8.9 g/dl
                          for women. Within 28 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 65000 /mm3 Within 28 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN Within 28 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN Within 28 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN Within 28 days prior
                          to study entry. ULN (Upper Limit of Normal).
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min Within 28
                          days prior to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70 Within 28 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   OTHER: Lipase <= 1.5 x ULN. Within 28 days
                          prior to study entry. Triglycerides >= 200
                          mg/dl; direct LDL-C >= 130 mg/dl (fasting 8
                          to 12 hours). Serum or plasma glucose <= 126
                          mg/dl (fasting 8 to 12 hours) within 28 days
                          prior to study entry. Creatine kinase <= 4.0
                          x ULN.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry Not pregnant Negative pregnancy
                          test prior to drug administration Abstinence
                          or agree to use condom, second barrier, and
                          hormonal birth control / contraception until
                          30 days after study.
PATIENT INCLUSION CRIT.   PRIOR TREATMENT: [Allowed: AS PER AMENDMENT
                          4/18/01: Cholecystectomy if performed more
                          than 3 months prior to study entry.].
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Alternative
                          therapies such as acupuncture and
                          visualization techniques (unless excluded by
                          the protocol). Patients should report the use
                          of these therapies; alternative therapies
                          will be recorded but not keyed.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Treatment with
                          potent antiretroviral therapy for more than 6
                          months. Patients must be on stable
                          antiretroviral therapy for at least 4 weeks
                          prior to study entry. Patients must be on
                          stable antiretroviral therapy for at least 8
                          weeks if they have changed from a protease
                          inhibitor (PI)-based regimen to a
                          non-PI-based regimen. [AS PER AMENDMENT
                          4/18/01: Any regimen without a PI must
                          provide adequate viral suppression, as
                          determined by the patient's physician.]
                          Allowed: 1. Zidovudine (ZDV). 2. Physiologic
                          doses of steroids (hormone replacement
                          therapy for postmenopausal women and for
                          transgendered patients will be allowed). 3.
                          Interleukin-2. 4. Systemic chemotherapy f
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. Zidovudine
                          (ZDV). 2. Physiologic doses of steroids. 3.
                          Interleukin-2. 4. Systemic chemotherapy for
                          KS. 5. Hydroxyurea (for the treatment of HIV
                          infection only). 6. Testosterone replacement
                          therapy for hypogonadism. Patients must be on
                          stable doses for at least 30 days prior to
                          study entry. Hormone replacement therapy for
                          postmenopausal women, for birth control, and
                          for transgendered patients will be allowed.
                          Patients must be on stable hormone
                          replacement therapy for 30 days prior to
                          study entry. 7. Treatment, maintenance, or
                          chemoprophylaxis with approved agents for OIs
                          as indicated unless prohibited in protocol.
                          8. Topical and oral antifungal agents, except
                          for oral ketoconazole and itraconazole. 9.
                          All antibiotics as clinically indicated
                          unless prohibited in protocol. 10. Regularly
                          prescribed medications such as antipyretics,
                          analgesics, allergy medications,
                          antidepressants, sleep medications, or any
                          other medications as medically indicated
                          (unless excluded by the protocol). 11.
                          Alternative therapies such as vitamins
                          (unless excluded by the protocol). Herbal
                          medications should be avoided. Patients
                          should report the use of these therapies;
                          alternative therapies will be recorded but
                          not keyed. [12. AS PER AMENDMENT 4/18/01:
                          Levothyroxine and liothyronine for uses other
                          than hypothyroidism.] [Recommended: AS PER
                          AMENDMENT 4/18/01: Every effort should be
                          made to retain patients on their original
                          antiretroviral regimen, especially for the
                          first 12 weeks. In the event that a patient
                          cannot tolerate 1 or more antiretroviral
                          medications or the antiretroviral regimen is
                          not efficacious, antiretroviral substitutions
                          may be made and do not require approval by
                          the protocol chair (with the exception of
                          investigational agents prohibited by this
                          protocol). Treatment interruptions are
                          allowed but discouraged during the first 12
                          weeks.].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Allergy/sensitivity to study drug(s) or any
                          medication related to statins and/or
                          fibrates. 2. Any coronary artery disease
                          including prior history of angina, myocardial
                          infarction, angioplasty, or bypass surgery;
                          or uncontrolled hypertension within 4 weeks
                          of study entry defined as systolic blood
                          pressure (SBP) greater than 180 mm Hg or
                          diastolic blood pressure (DBP) greater than
                          115 mm Hg. 3. Rhabdomyolysis. 4. Severe
                          hepatic dysfunction (e.g., end-stage liver
                          disease secondary to hepatitis B or C). [5.
                          AS PER AMENDMENT 4/18/01: Active or
                          symptomatic] gall bladder disease [AS PER
                          AMENDMENT 4/18/01: within 3 months of study
                          entry or symptomatic gallstones]. 6. Failed
                          previous statin or fibrate therapy (after 24
                          weeks of treatment) or had an adverse
                          reaction to these agents. Patients are
                          considered to have failed their previous
                          therapy if they had not achieved all 3 of the
                          following conditions: LDL levels of 100 mg/dl
                          or less (for patients with 2 or more
                          cardiovascular risk factors) or less than 130
                          mg/dl (for patients with fewer than 2 risk
                          fact
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse or dependence which, in the
                          opinion of the investigator, would interfere
                          with adherence to study requirements.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: 1. Radiation
                          therapy within 30 days of study entry. 2. Any
                          experimental therapy (not FDA-approved)
                          within 14 days prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any
                          experimental therapy (not FDA-approved)
                          within 14 days prior to study entry. 2. Any
                          [AS PER AMENDMENT 4/18/01: prescription]
                          lipid-lowering agent (cerivastatin,
                          cholestyramine, colestipol, dextrothyroxine,
                          fluvastatin, gemfibrozil, lovastatin,
                          atorvastatin, simvastatin, etc.) or
                          non-prescription lipid-lowering agents that
                          have statin effects within 14 days prior to
                          screening, including niacin in doses of 1
                          g/day or higher. Patient must not have been
                          on any lipid-lowering agent for over 24 weeks
                          in the past. 3. Drugs that may increase the
                          risk of myopathy or rhabdomyolysis (e.g.,
                          cyclosporine, erythromycin, itraconazole,
                          ketoconazole, [AS PER AMENDMENT 4/18/01: the
                          following text has been deleted:
                          levothyroxine]) within 14 days prior to study
                          entry. [AS PER AMENDMENT 4/18/01:
                          Levothyroxine and liothyronine for
                          hypothyroidism are prohibited.] 4. Creatine
                          monophosphate or immunomodulating therapy
                          within 30 days prior to study entry. [5. AS
                          PER AMENDMENT
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antidiabetic medications, including but not
                          limited to insulin, acetohexamide,
                          chlorpropamide, glimepiride, glipizide,
                          glyburide, tolazamide, acarbose, metformin,
                          rosiglitazone, and pioglitazone. 2. [AS PER
                          AMENDMENT 4/18/01: Prescription]
                          lipid-lowering agents (e.g., cerivastatin,
                          cholestyramine, colestipol, dextrothyroxine,
                          fluvastatin, gemfibrozil, lovastatin,
                          atorvastatin, simvastatin) [AS PER AMENDMENT
                          4/18/01: other than those provided by the
                          study and non-prescription lipid-lowering
                          agents, such as garlic supplements]. 3.
                          Niacin in lipid-lowering doses of 1 g/day or
                          more. 4. Testosterone doses exceeding those
                          for physiologic replacement therapy. 5. Drugs
                          that may increase the risk of myopathy or
                          rhabdomyolysis (e.g., cyclosporine,
                          erythromycin, itraconazole, ketoconazole, [AS
                          PER AMENDMENT 4/18/01: the following text has
                          been deleted: levothyroxine]). [AS PER
                          AMENDMENT 4/18/01: Levothyroxine and
                          liothyronine for hypothyroidism are
                          prohibited.]
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Allergy/sensitivity to study drug(s) or any
                          medication related to statins and/or
                          fibrates. 2. Diabetes mellitus requiring
                          medical therapy. [AS PER AMENDMENT 4/18/01:
                          Diet-controlled diabetes mellitus is
                          allowed.] 3. Hypothyroidism (treated or
                          untreated), per patient's medical records. 4.
                          Co-enrollment in ACTG A5055, A5082, [AS PER
                          AMENDMENT 4/18/01: or studies with scheduled
                          treatment interruptions (including, but not
                          limited to, ACTG 371, A5024, A5057/A5120,
                          A5068, A5086, A5102, A5130, and A5132)].
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0319  Pravastatin sodium
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0333  Fenofibrate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm B: 40 mg qd.
                          Drug 2: Arm A: 200 mg qd
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Arm B: 40 mg. Drug 2:
                          Arm A: 200 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: A composite examination of the
                          absolute values for LDL, TG, HDL at Week 12;
                          changes in laboratory parameters from
                          baseline (entry) at Week 12; prevalence of
                          adverse events.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Refusal of further
                          treatment and/or follow-up evaluations by
                          patient or legal guardian. 2. Determination
                          by the investigator that further
                          participation would be detrimental to the
                          patient's health or well-being. 3. Failure to
                          comply with the study requirements so as to
                          cause harm to self or seriously interfere
                          with the validity of the study results. 4.
                          Treatment required with medications that are
                          disallowed while on this study. 5. Failure to
                          initiate dual-agent lipid-lowering therapy at
                          Week 16 if required. 6. Drug toxicity as
                          defined in the protocol. 7. Pregnancy. 8. Two
                          consecutive clinic visits missed or failure
                          to take study medications as prescribed
                          without reasonable cause, as determined by
                          the investigator. 9. Generalized debilitation
                          or transfer to nursing home or hospice such
                          that follow-up visits and administration of
                          study medication are no longer possible.
OTHER TREATMENT INFO.     MODIFICATION: There will be no dose
                          interruptions, modifications, or
                          discontinuations for any Grade 1 or 2
                          toxicity (except for creatinine) as defined
                          by the DAIDS Adult Toxicity Table. Dose
                          interruptions will be made for drug
                          toxicities of Grade 3 or higher as defined in
                          the protocol.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 010727.
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010727.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 010727.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010727.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010727.
CALIFORNIA                San Francisco VA Med Ctr 3180 18th St San
                          Francisco, CA 941104206 Julieann Lewis
                          [phone] Recruiting 010727.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 010727.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 010727.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Mario Guerrerro
                          [phone] Recruiting 010727.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 010727.
COLORADO                  Denver Dept of Health and Hosps 4200 East 9th
                          Ave / Campus Box B-196 Denver, CO 80262 M
                          Graham Ray [phone] Recruiting 010727.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010727.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 010727.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Beth Dean [phone] Recruiting
                          010727.
HAWAII                    Tripler Army Med Ctr Infectious Disease
                          Services MCHK-DMI / One Jarrett White Rd
                          Tripler AMC, HI 96859 Ross Newmann
                          [phone] Recruiting 010727.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010727.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 010727.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010727.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010727.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010727.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010727.
MASSACHUSETTS             Brigham and Women's Hosp Div of Infectious
                          Diseases / 15 Francis St PBB A-4 Boston, MA
                          02215 Carolyn Koziol [phone] Recruiting
                          010727.
MASSACHUSETTS             Harvard (Massachusetts Gen Hosp) 55 Fruit St
                          / Founders Bldg 8th Floor Boston, MA 02114
                          Teri Flynn [phone] Recruiting 010727.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 010727.
MASSACHUSETTS             Boston Med Ctr 1 Boston Med Ctr Place /
                          Dowling Bldg Boston, MA 02118 Beth Hankin
                          [phone] Recruiting 010727.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Charles Raines
                          [phone] Recruiting 010727.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 010727.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010727.
NORTH CAROLINA            Moses H Cone Memorial Hosp 1200 North Elm St
                          Greensboro, NC 27401 Lisa Dasnoit
                          [phone] Recruiting 010727.
NORTH CAROLINA            Carolinas Med Ctr 1000 Blythe Blvd / MEB 202
                          Charlotte, NC 28203 Marjorie Massey
                          [phone] Recruiting 010727.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 010727.
NEBRASKA                  Univ of Nebraska Med Ctr 985130 Nebraska Med
                          Ctr Omaha, NE 681985130 Frances Van Meter
                          [phone] Recruiting 010727.
NEW YORK                  St Mary's Hosp (Univ of Rochester/Infectious
                          Diseases) 601 Elmwood Ave Rochester, NY 14642
                          Carol Greisberger [phone] Recruiting
                          010727.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 010727.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010727.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 010727.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Ross Hewitt
                          [phone] Recruiting 010727.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] Recruiting 010727.
NEW YORK                  Cornell Clinical Trials Unit 119 West 24th St
                          / Ground Floor New York, NY 10011 Todd
                          Stroberg [phone] Recruiting 010727.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 010727.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010727.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Valery Hughes [phone]
                          Recruiting 010727.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 010727.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010727.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 010727.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 010727.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 010727.
PENNSYLVANIA              Univ of Pennsylvania 536 Johnson Pavillion
                          Philadelphia, PA 19104 Joseph Quinn
                          [phone] Recruiting 010727.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          010727.
PENNSYLVANIA              Philadelphia Veterans Administration Med Ctr
                          536 Johnson Pavilion Philadelphia, PA 19104
                          Joseph Quinn [phone] Recruiting 010727.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 010727.
RHODE ISLAND              Brown Univ / Miriam Hosp 164 Summit Ave /
                          Immunology Ctr Providence, RI 02906 Joan
                          Gormley [phone] Recruiting 010727.
RHODE ISLAND              Rhode Island Hosp / Brown Univ 593 Eddy St
                          Providence, RI 02903 Carolyn Dwyer
                          [phone] Recruiting 010727.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 010727.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 010727.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone]
                          Recruiting 010727.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 010727.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010727.

67
UNIQUE IDENTIFIER         FDA/01323
PROTOCOL ID NUMBERS       FDA 228H
PROTOCOL TITLE            A Randomized, Open-Label Study to Evaluate 3
                          Salvage Regimens in HIV-Infected Subjects
                          Experiencing Virologic Failure on an Initial
                          HAART Regimen Containing Nelfinavir.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and efficacy
                          of 3 salvage regimens in HIV-positive
                          patients experiencing virologic failure on an
                          initial antiretroviral regimen containing
                          nelfinavir (NFV).
GENERAL DESCRIPTION       RATIONALE:
GENERAL DESCRIPTION       METHODOLOGY: Patients receive 1 of 3 salvage
                          regimens. Treatments A and B include
                          delavirdine, 1 of 2 doses of indinavir, and 2
                          nucleoside reverse transcriptase inhibitors
                          (NRTIs) to which the patient has not been
                          exposed. Treatment C includes ritonavir,
                          indinavir, and 2 NRTIs to which the patient
                          has not been exposed. When virologic failure
                          is first observed, the patient must return in
                          2 weeks for confirmation of failure and start
                          the salvage regimen within 1 month of the
                          first assay in which failure was observed.
                          Patients who have less than 400 copies/ml HIV
                          RNA after 16 weeks of therapy are considered
                          responders and continue on the study. Those
                          who have more than 400 copies/ml after 16
                          weeks of therapy are considered nonresponders
                          and should be discontinued from the study. In
                          addition, patients who respond and
                          subsequently rebound with a viral load 0.5
                          log above the nadir and greater than 400
                          copies/ml on 2 consecutive assays at least 2
                          weeks apart are considered treatment failures
                          and should be discontinued from the study.
                          Patients have regular physical exams, as well
                          as virologic, immunologic, and
                          pharmacokinetic assessments.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010711)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy, Drug
                          safety, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/60.
PROTOCOL DETAILS          STUDY DURATION: 18 months.
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AG1343-1133. 1133
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection. 2. Have an undetectable
                          viral load (less than 400 copies/ml) followed
                          by virologic rebound on an initial regimen
                          containing NFV. Patients must return within 2
                          weeks for confirmation of virologic failure.
                          3. Have viral load of less than 30,000
                          copies/ml at entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Initial
                          antiretroviral regimen containing NFV.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Study
                          regimen must be started within 1 month of the
                          first assay in which failure was observed.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Nonnucleoside
                          reverse transcriptase inhibitors (NNRTIs) and
                          protease inhibitors (PIs) except NFV.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0166  Delavirdine mesylate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Treatments A and B:
                          600 mg bid. Drug 2: Treatment A and C: 800 mg
                          bid. Treatment B: 1200 mg bid. Drug 3:
                          Treatment C: 200 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 1200 mg. Drug 2:
                          Treatment A and C: 1600 mg. Treatment B: 2400
                          mg. Drug 3: 400 mg
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients who have more than 400
                          copies/ml after 16 weeks of therapy are
                          considered nonresponders and should be
                          discontinued from the study. In addition,
                          patients who respond and subsequently rebound
                          with a viral load 0.5 log above the nadir and
                          greater than 400 copies/ml on 2 consecutive
                          assays at least 2 weeks apart are considered
                          treatment failures and should be discontinued
                          from the study.
SUPPORTING AGENCY         Agouron Pharmaceuticals Inc.
LAST REVISION DATE        20010711

68
UNIQUE IDENTIFIER         NIH/01320
PROTOCOL ID NUMBERS       NIAID ACTG A5038
PROTOCOL TITLE            Discontinuation of Antifungal Therapy for
                          Histoplasmosis Following Immunologic Response
                          to Antiretroviral Therapy.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine if maintenance therapy
                          for histoplasmosis can be discontinued with
                          relapse rates below 20 percent.
GENERAL DESCRIPTION       RATIONALE: Histoplasmosis is a serious
                          opportunistic infection in persons with AIDS
                          that demonstrates an excellent response to
                          antifungal therapy. However, until the advent
                          of highly active antiretroviral therapy
                          (HAART), patients with histoplasmosis
                          required lifelong suppressive antifungal
                          therapy. It is thought that immune
                          reconstitution as a result of HAART may
                          diminish the need for chronic therapy.
                          Histoplasmosis offers an opportunity to
                          examine the concept of discontinuation of
                          maintenance therapy as it is rapidly
                          diagnosed and effectively treated with
                          itraconazole [AS PER AMENDMENT 9/27/00: or
                          other appropriate therapy for disseminated
                          histoplasmosis] should relapse occur.
GENERAL DESCRIPTION       METHODOLOGY: Patients discontinue antifungal
                          maintenance therapy. Patients are seen for
                          routine visits every 8 weeks and urine and
                          serum specimens are collected for real time
                          Histoplasma antigen testing and immunologic
                          parameters. Patients with suspected
                          recurrence, as determined by clinical or
                          routine laboratory findings consistent with
                          recurrent histoplasmosis, are reevaluated
                          within 1 week of onset of these findings.
                          Patients with suspected recurrence based on a
                          serum or urine Histoplasma antigen rise of 2
                          units or more, in the absence of clinical or
                          routine laboratory findings consistent with
                          histoplasmosis, are reevaluated within 2
                          weeks. All patients with suspected recurrence
                          have more frequent evaluations and additional
                          laboratory tests. Those with negative studies
                          resume bimonthly follow-up. All patients who
                          develop proven (positive culture or positive
                          fungal stain of tissues or body fluids) or
                          probable relapse (clinical findings of
                          relapse with an increase in antigen of 4.1
                          units or more, or no clinical findings but
                          increases in antigen levels on repeated
                          testing with the most recent antigen test
                          demonstrating an increase in antigen of 4.1
                          units or more) or who experience persistent
                          reduction of CD4 cell count to below 100/mm3
                          have antifungal induction therapy
                          reinstituted. Patients remain on study for at
                          least 12 months with regular
                          follow-up/evaluations.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Secondary prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 50 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 months after
                          enrollment of the last patient.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 32/50 010403.
PROTOCOL DETAILS          STUDY DURATION: 24 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 13
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (000927)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5038
PROTOCOL DETAILS          STUDY DESIGN: Withdrawal Study; Longitudinal
                          Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection as documented by a
                          positive ELISA from a licensed kit with
                          confirmation by Western blot or a positive
                          HIV culture or detection of HIV-1 RNA or HIV
                          antigen. 2. Have previous diagnosis of
                          histoplasmosis as documented by recovery of
                          H. capsulatum from cultures or identification
                          of yeast forms consistent with H. capsulatum
                          in stains or detection of high levels of
                          Histoplasma antigen (4.1 units or more) in
                          body fluids (urine, serum, bronchoalveolar
                          lavage fluid). 3. Have consent of a parent or
                          guardian if under 18 years of age. 4. Have 2
                          CD4 cell counts above 150 cells/mm3 (1 of
                          which has been obtained within 6 months and
                          the other within 30 days before entry). Note:
                          The 2 CD4 counts used for eligibility must be
                          from tests performed at least 1 week apart.
                          5. Have laboratory remission from
                          disseminated histoplasmosis [AS PER AMENDMENT
                          9/27/00: The following text has been deleted:
                          after at least 12 consecutive months of
                          treatment with itraconazole (or, for other
                          antifungal, contact the protocol co-chair for
                          eligibility)] supported by Histoplasma
                          antigen concentrations in urine and serum
                          below 4.1 units. 6. Have a negative pregnancy
                          test within 14 days of study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 150 cells/mm3 Two
                          tests must yield counts > 150 cells/mm3 (1 of
                          which has been obtained within 6 months and
                          the other within 30 days before entry). Note:
                          The 2 CD4 counts used for eligibility must be
                          from tests performed at lea
PATIENT INCLUSION CRIT.   OTHER: Histoplasma antigen < 4.1 units.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test within 14 days of study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: 1. Antiretroviral
                          therapy for at least 24 consecutive weeks and
                          a stable antiretroviral regimen for at least
                          8 weeks before entry. A stable regimen is
                          defined as receiving the same antiretroviral
                          drugs during that time period with dose
                          adjustments allowed. 2. Itraconazole [AS PER
                          AMENDMENT 9/27/00: or other appropriate
                          therapy for disseminated histoplasmosis] for
                          at least 12 consecutive months before study
                          entry. [AS PER AMENDMENT 9/27/00: Patients
                          who receive less than 12 consecutive months
                          of itraconazole or other appropriate therapy
                          for disseminated histoplasmosis because of
                          therapy interruptions of less than 4 weeks in
                          duration will remain eligible for study e
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: [Required: AS PER
                          AMENDMENT 9/27/00: Itraconazole or other
                          appropriate maintenance therapy for
                          disseminated histoplasmosis currently or has
                          discontinued itraconazole or other
                          appropriate maintenance therapy for
                          disseminated histoplasmosis within 24 weeks
                          of study entry.] Allowed: 1. Systemic
                          antifungal therapies episodically (continuous
                          duration of 4 weeks or less) for the
                          treatment of oropharyngeal or esophageal
                          candidiasis or dermatophyte infection. 2.
                          Hydroxyurea. 3. Granulocyte
                          colony-stimulating factor. [4. AS PER
                          AMENDMENT 9/27/00: Corticosteroids at
                          physiologic doses will be permitted.].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Presence of unexplained clinical or
                          laboratory findings consistent with relapse
                          of histoplasmosis within 4 weeks of study
                          entry. 2. Requirement for continued treatment
                          with itraconazole, intravenous amphotericin
                          B, fluconazole, ketoconazole, or any other
                          systemic antifungal therapy for other fungal
                          infections.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Immunosuppressive medications, including
                          chemotherapy or corticosteroids [AS PER
                          AMENDMENT 9/27/00: at supraphysiologic doses
                          for more than 2 weeks], within the last 2
                          months. [AS PER AMENDMENT 9/27/00: Use of
                          corticosteroids at physiologic doses will be
                          permitted.] 2. Immunostimulatory therapy
                          (e.g., IL-2) during the last 2 months. [AS
                          PER AMENDMENT 9/27/00: This criterion has
                          been removed.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: IL-2 at any
                          time during the trial. [AS PER AMENDMENT
                          9/27/00: This criterion has been removed.].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active systemic infection. Patients on stable
                          chronic suppressive therapy (e.g.,
                          cytomegalovirus [CMV], Mycobacterium avium
                          complex [MAC]) for at least 3 months will be
                          eligible. 2. Meningitis or lesion of brain or
                          spinal cord thought to be caused by H.
                          capsulatum infection. 3. Presence of
                          unexplained clinical or laboratory findings
                          consistent with relapse of histoplasmosis. 4.
                          Requirement for continued treatment with
                          itraconazole, intravenous amphotericin B,
                          fluconazole, ketoconazole, or any other
                          systemic antifungal therapy for other fungal
                          infections.
OTHER TREATMENT INFO.     END POINT: Proven or probable relapse of
                          histoplasmosis at any time over the course of
                          the study.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Completion of the
                          protocol-specified follow-up period. 2.
                          Protocol-described endpoints. 3. Death. 4.
                          Patient or physician elects to discontinue
                          follow-up.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                San Francisco VA Med Ctr 3180 18th St San
                          Francisco, CA 941104206 Julieann Lewis
                          [phone] No longer recruiting 001121.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 000906.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Beth Dean [phone] Recruiting
                          001109.
ILLINOIS                  Cook County Hosp 1835 W Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 001109.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 001109.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 001109.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 001109.
NEBRASKA                  Univ of Nebraska Med Ctr 985130 Nebraska Med
                          Ctr Omaha, NE 681985130 Frances Van Meter
                          [phone] Recruiting 000906.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 001109.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 001109.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 001109.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 000906.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 001109.

69
UNIQUE IDENTIFIER         NIH/01315
PROTOCOL ID NUMBERS       NIAID HIVNET 021
PROTOCOL TITLE            Hormonal Contraception and the Risk of HIV
                          Acquisition.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To measure the effect of combined
                          oral contraceptive (COC) and
                          Depot-Medroxyprogesterone Acetate (DMPA) use
                          on the acquisition of HIV infection by
                          comparing the rate of infection among women
                          using COCs and DMPA with the rate among women
                          not using hormonal contraception.
GENERAL DESCRIPTION       RATIONALE: Heterosexual intercourse is the
                          primary mode of HIV transmission worldwide
                          and accounts for about 90% of HIV infections
                          in women. Hormonal contraceptives including
                          COCs and injectables are among the most
                          widely used contraceptives in the world.
                          Understanding the impact of hormonal
                          contraception on HIV transmission is a
                          critical unanswered public health question.
                          Because of the critical nature of this issue
                          to women of reproductive age worldwide, a
                          methodologically sound study must be
                          undertaken. It must be determined if hormonal
                          contraceptive use increases the risk of HIV
                          infection and the magnitude of the
                          association, if it exists.
GENERAL DESCRIPTION       METHODOLOGY: This study takes place in
                          Thailand, Uganda, and Zimbabwe.
                          HIV-seronegative women continue using their
                          current birth control method (low dose COC,
                          DMPA injections, or non-hormonal
                          contraceptive methods [condoms,
                          sterilization, or no modern contraception
                          method]) for the duration of the study. They
                          are followed every 12 weeks for a minimum of
                          15 months and a maximum of 24 months, or
                          until seroconversion. Pelvic exams, including
                          Pap smears, are done, blood samples are
                          drawn, and vaginal and cervical specimens are
                          tested for any sexually transmitted diseases
                          (STDs). Women are provided with free
                          treatment for any STDs that are diagnosed.
                          They complete a questionnaire on sexual
                          behavior and contraceptive history;
                          counseling on contraceptive use and reducing
                          HIV risk is provided.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Adverse effects.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 6360 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 15 months to 24
                          months or until seroconversion.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 4569/6360 010731.
PROTOCOL DETAILS          STUDY DURATION: 36 months.
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (991214)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Women must: 1. Be
                          attending family planning and maternal and
                          child health clinics in Zimbabwe, Thailand,
                          or Uganda. 2. Be using low-dose COCs or DMPA
                          for at least 3 months with the intention to
                          continue for the next 12 months, or
                          non-hormonal contraception (condoms,
                          sterilization), or no modern contraceptive
                          method. 3. Have HIV seronegativity. 4. Be
                          sexually active (at least 3 coital episodes
                          in the last 3 months). 5. Be at least 4.5
                          months post-partum, if parous. 6. Agree to
                          all study procedures, including HIV testing
                          every 3 months, follow-up clinic visits, and
                          home visits if they fail to return for
                          follow-up. 7. Be able to provide a home
                          address sufficient and accessible for
                          follow-up purposes.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Low-dose COCs for
                          at least 3 months with the intention to
                          continue for the next 12 months, or DMPA for
                          at least 3 months with the intention to
                          continue for the next 12 months, or
                          non-hormonal contraception (condoms,
                          sterilization) or no modern contraceptive
                          method.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Low-dose
                          COCs with the intention to continue for the
                          next 12 months, or DMPA with the intention to
                          continue for the next 12 months, or
                          non-hormonal contraception (condoms,
                          sterilization) or no modern contraceptive
                          method.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 16
                          years less than or equal to 35 years.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Women with the
                          following prior conditions are excluded: 1.
                          Not currently using COCs or DMPA but have
                          used COCs within the last 3 months, or DMPA
                          within the previous 6 months. 2.
                          HIV-indeterminate or HIV-positive. 3. Have
                          used an IUD for contraception in the last
                          month. 4. Full hysterectomy. 5. Spontaneous
                          or induced abortion within the last month. 6.
                          Previous participation in an HIV vaccine
                          trial.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Injection of illicit
                          drugs within the last 3 months.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Blood transfusion
                          within the last 3 months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Use of hormonal
                          contraceptive other than COCs or DMPA (such
                          as Norplant, NET-EN, or progestin-only pills)
                          within the last 3 months.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Pregnant or
                          intention to become pregnant in the
                          subsequent 12 months. Women who become
                          pregnant after recruitment will not be
                          discontinued from the cohort. 2. Current
                          participation in an HIV vaccine trial.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0331  Ethinyl
                          estradiol/levonorgestrel
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0332  Medroxyprogesterone acetate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 2: 100 mg every 12
                          weeks
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2:
                          Intramuscular
OTHER TREATMENT INFO.     END POINT: Acquisition of an incident HIV
                          infection, defined as a positive HIV test
                          result in a previously HIV seronegative
                          woman.
OTHER TREATMENT INFO.     DISCONTINUE: Women may be discontinued for
                          the following reasons: 1. Patient's decision.
                          2. Study doctor decides that it is in the
                          patient's best interest for her safety and/or
                          well-being. 3. Non-compliance. 4. Patient
                          experiences a serious adverse experience.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726

70
UNIQUE IDENTIFIER         FDA/01314
PROTOCOL ID NUMBERS       FDA 285G
PROTOCOL TITLE            A Phase I/II, Open Label Study to Evaluate
                          the Ability of Combination Therapy with
                          ABT-378/Ritonavir (Kaletra), Lamivudine
                          (Epivir), Efavirenz (Sustiva), and Tenofovir
                          DF to Completely Suppress Viral Replication
                          in Subjects Infected with HIV-1.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine whether treatment with
                          a novel 4-drug antiretroviral regimen can
                          completely suppress viral replication in
                          patients with newly acquired HIV-1 infection
                          (within 90 days of infection) and in patients
                          with chronic HIV-1 infection and wild-type
                          virus by genotype and phenotype, as
                          determined by the use of standard and novel
                          virologic assays. Methodology: Patients
                          receive ABT-378/ritonavir (ABT-378/r) plus
                          lamivudine twice daily and efavirenz plus
                          tenofovir DF once daily. Patients receive
                          study drug for at least 96 weeks on an
                          outpatient basis.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive
                          ABT-378/ritonavir (ABT-378/r) plus lamivudine
                          twice daily and efavirenz plus tenofovir DF
                          once daily. Patients receive study drug for
                          at least 96 weeks on an outpatient basis.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010711)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug therapy, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 44 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 40/44 010716.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: M00-154
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have within 30 days prior to the initial
                          dose: 1. HIV-1 infection by 1 of the
                          following criteria: (a) Acute infection as
                          defined by a positive plasma HIV-1 RNA by
                          either RT-PCR (Roche) or signal amplification
                          (bDNA, Chiron) and 1 of the following: absent
                          HIV-1 antibody by ELISA; positive ELISA and
                          an evolving Western blot (minimum of 2 bands)
                          or clinical history consistent with HIV-1
                          infection and a documented negative serology
                          HIV-1 within 120 days of screening; or (b)
                          HIV-1 infection for greater than 90 days by
                          serology and plasma HIV-RNA determinations
                          with baseline drug susceptibility testing
                          indicating susceptibility to all classes of
                          agents. 2. Life expectancy of 1 year or more.
                          3. Vital signs, physical examination, and
                          laboratory results that do not exhibit signs
                          of acute illness other than HIV infection.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN Unless secondary to
                          primary HIV infection, in the opinion of the
                          investig
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN Unless secondary to
                          primary HIV infection, in the opinion of the
                          investigator.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70 Within 30 days prior to
                          initial dose.
PATIENT INCLUSION CRIT.   OTHER: Serum phosphate >= 2.2 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 30 days after Negative
                          pregnancy test within 30 days of initial drug
                          administration.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 65 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Psychiatric illness that would preclude
                          compliance with the protocol. 2. Significant
                          renal or bone disease. 3. New AIDS-defining
                          condition diagnosed within 30 days prior to
                          baseline. 4. Active, serious infections
                          (other than HIV-1 infection) requiring
                          parenteral antibiotic therapy within 15 days
                          prior to screening.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: 1. Use of alcohol
                          during the study or within 30 days of the
                          initial dose without consent of principal
                          investigator. 2. History of substance abuse
                          that would preclude compliance with the
                          protocol.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 30 days prior to initial dose, without
                          consent of Abbott medical monitor.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy, without consent of Abbott medical
                          monitor.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 30 days of
                          baseline: 1. Systemic therapy for KS. 2.
                          Medications contraindicated for tenofovir DF:
                          nephrotoxic agents such as aminoglycoside
                          antibiotics, amphotericin B, cidofovir,
                          cisplatin, foscarnet, IV pentamidine,
                          vancomycin, oral or IV ganciclovir, other
                          agents with nephrotoxic potential such as
                          probenecid, systemic chemotherapeutic agents,
                          and systemic corticosteroids. Excluded within
                          30 days prior to initial dose: 1. Medications
                          contraindicated for ABT-378/r: terfenadine,
                          dihydroergotamine, rifampin, lovastatin,
                          simvastatin, pimozide, and St. John's wort.
                          2. Medications contraindicated for ACT-378/r
                          and efavirenz: midazolam, triazolam,
                          astemizole, cisapride, and ergot derivatives.
                          3. Any medication, including over-the-counter
                          medicine, without the consent of principal
                          investigator. 4. Any other experimental
                          agents, antiretroviral drugs, or
                          immunomodulators without the consent of the
                          Abbott medical monitor.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Medications contraindicated for ABT-378/r:
                          terfenadine, dihydroergotamine, rifampin,
                          lovastatin, simvastatin, pimozide, and St.
                          John's wort. 2. Medications contraindicated
                          for ACT-378/r and efavirenz: midazolam,
                          triazolam, astemizole, cisapride, and ergot
                          derivatives. 3. Medications contraindicated
                          for tenofovir DF: nephrotoxic agents such as
                          aminoglycoside antibiotics, amphotericin B,
                          cidofovir, cisplatin, foscarnet, IV
                          pentamidine, vancomycin, oral or IV
                          ganciclovir, other agents with nephrotoxic
                          potential such as probenecid, systemic
                          chemotherapeutic agents, and systemic
                          corticosteroids. 4. Any medication, including
                          over-the-counter medicine, without the
                          consent of principal investigator. 5. Any
                          other experimental agents, antiretroviral
                          drugs, or immunomodulators without the
                          consent of the Abbott medical monitor. 6.
                          Systemic therapy for KS.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Inability to comply with the study protocol
                          or lack of suitability, as determined by
                          investigator. 2. Gastrointestinal
                          malabsorption syndrome or chronic nausea or
                          vomiting which may confer an inability to
                          receive an orally administered medication. 3.
                          Malignancy other than cutaneous Kaposi's
                          sarcoma (KS) or basal cell carcinoma.
                          (Patients with biopsy-confirmed cutaneous KS
                          are eligible, but must not have received any
                          systemic therapy for KS within 30 days of
                          baseline and are not anticipated to require
                          systemic therapy during the study.).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0269  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0290  Tenofovir disoproxil
                          fumarate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0316  Lopinavir/Ritonavir
RESULTS                   Louie M, Ramratnam B, Kost R, Hurley A, Zhang
                          L, Sun E, Brun S, Mcgowan I, Ruiz N, Ho DD,
                          Markowitz M. 8th Conf Retro and Opportun
                          Infect. 2001 Feb 4-8 (abstract no. 383).
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 150 mg bid. Drug 2:
                          600 mg qd. Drug 3: 300 mg qd. Drug 4: 533
                          mg/133 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 300 mg. Drug 2: 600 mg.
                          Drug 3: 300 mg. Drug 4: 1066 mg/266 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 96 weeks.
SUPPORTING AGENCY         Abbott Laboratories.
LAST REVISION DATE        20010711
NEW YORK                  Aaron Diamond AIDS Rsch Ctr / Rockefeller
                          Univ 1230 York Ave New York, NY 10021
                          Kimberly J Kailer [phone] Recruiting
                          000804.

71
UNIQUE IDENTIFIER         FDA/01313
PROTOCOL ID NUMBERS       FDA 285F
PROTOCOL TITLE            A Randomized, Open-Label, Phase II Study of
                          High Dose ABT-378/Ritonavir and Standard Dose
                          ABT-378/Ritonavir with Additional Ritonavir
                          in Protease Inhibitor and Non-Nucleoside
                          Reverse Transcriptase Inhibitor-Experienced
                          HIV-Infected Subjects.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To characterize the safety,
                          tolerability, and pharmacokinetics of
                          high-dose ABT-378/ritonavir and of
                          ABT-378/ritonavir at the proposed standard
                          dose administered in combination with
                          additional ritonavir. To assess the antiviral
                          activity of high-dose ABT-378/ritonavir and
                          ABT-378/ritonavir at the proposed standard
                          dose with additional ritonavir. Methodology:
                          Patients are randomized equally to 1 of 2
                          treatment arms. One arm receives 5
                          coformulated capsules of ABT-378/ritonavir
                          twice daily. The other arm receives 3
                          coformulated capsules of ABT-378/ritonavir
                          plus 2 ritonavir capsules twice daily.
                          Pharmacokinetic samples are collected on Day
                          21 and analyzed. Patients receive study drug
                          for at least 48 weeks on an outpatient basis.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized equally
                          to 1 of 2 treatment arms. One arm receives 5
                          coformulated capsules of ABT-378/ritonavir
                          twice daily. The other arm receives 3
                          coformulated capsules of ABT-378/ritonavir
                          plus 2 ritonavir capsules twice daily.
                          Pharmacokinetic samples are collected on Day
                          21 and analyzed. Patients receive study drug
                          for at least 48 weeks on an outpatient basis.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010614)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy, Drug
                          safety, Drug tolerance, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 36 patients.
                          Approximately.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 48
                          weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 17/36 010220.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 7
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: M99-049
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have within 45 days prior to initial dosing:
                          1. HIV positivity. 2. Vital signs, physical
                          exam, and laboratory results that do not
                          exhibit evidence of acute illness. 3. Plasma
                          viral load greater than 1000 copies/ml. 4.
                          CD4 count less than 200 cells/mm3.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 20000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 200 cells/mm3 Within
                          45 days prior to initial dosing.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70 Within 45 days prior to
                          initial dosing.
PATIENT INCLUSION CRIT.   OTHER: Hepatitis BsAG (-) or HCV antibody
                          (-).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Negative pregnancy test within 30 days
                          of initial drug administration.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required within 45 days
                          prior to initial dosing: Previous therapy
                          with at least 2 protease inhibitors and at
                          least 1 nonnucleoside reverse transcriptase
                          inhibitor.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Intolerance to ritonavir dose of 300 mg twice
                          daily. 2. Pancreatitis.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Use of alcohol
                          during study and within 45 days prior to
                          initial dosing without the knowledge of the
                          principal investigator.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Treatment for
                          an active AIDS-defining opportunistic
                          infection within 15 days of screening. 2.
                          Investigational drugs within 30 days prior to
                          screening. 3. Midazolam, triazolam,
                          terfenadine, astemizole, cisapride, pimozide,
                          antimigraine ergot derivatives (ergotamine,
                          dihydroergotamine), rifampin, lovastatin,
                          simvastatin, and hypericum perforatum (St.
                          John's wort) within 45 days prior to initial
                          dosing. 4. Any medication, including
                          over-the-counter medicine, within 45 days
                          prior to initial dosing without the knowledge
                          of the principal investigator.
                          Contraindicated for patients taking
                          ritonavir: Quinidine, propafenone,
                          flecainide, amiodarone, and bepridil within
                          45 days prior to initial dosing.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Midazolam, triazolam, terfenadine,
                          astemizole, cisapride, pimozide, antimigraine
                          ergot derivatives (ergotamine,
                          dihydroergotamine), rifampin, lovastatin,
                          simvastatin, and hypericum perforatum (St.
                          John's wort). 2. Any medication, including
                          over-the-counter medicine, without the
                          knowledge of the principal investigator.
                          Contraindicated for patients taking
                          ritonavir: Quinidine, propafenone,
                          flecainide, amiodarone, and bepridil.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Any
                          condition that, in the opinion of the
                          principal investigator, makes the patient
                          unlikely to comply with the study protocol or
                          unsuitable for any other reason.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0316  Lopinavir/Ritonavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Treatment Arm 1: 667
                          mg/167 mg bid. Treatment Arm 2: 400 mg/100 mg
                          bid. Drug 2: Treatment Arm 2: 200 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Treatment Arm 1: 1334
                          mg/334 mg. Treatment Arm 2: 800 mg/200 mg.
                          Drug 2: Treatment Arm 2: 400 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 48 weeks.
SUPPORTING AGENCY         Abbott Laboratories.
LAST REVISION DATE        20010614
CALIFORNIA                UCSD Treatment Ctr 2760 5th Ave / Suite 300
                          San Diego, CA 92103 Denise Elkins
                          [phone] Recruiting 000816.
MARYLAND                  Johns Hopkins Hosp 600 N Wolfe St / Osler 525
                          Baltimore, MD 21287 Michelle Parish
                          [phone] Recruiting 010723.
OTHER                     Ciutat Santaria De Bellvitge / Edificio
                          Antigua Escuela 3a Planta / Feixa Llarga S/N
                          / L'Hospitalet Barcelona, Elena Ferrer
                          (932)607-668 Recruiting 000816.
OTHER                     Hopital Europeen George Pompidou Service
                          d'Immunoligie Clinique / 20 rue Leblanc 75908
                          Paris, Nafissa Bengait (331)560-93297
                          Recruiting 010220.
OTHER                     Hopital Pitie Salpetriere / Service des
                          Maladies Infe 47 Boulevard de L'Hopital /
                          CEDEX 13 Paris, Dr Tubiana (142)160-130
                          Recruiting 000816.
OTHER                     Hopital Pitie Salpetriere / Medecine Interne
                          47-83 Boulevard de L Hopital / CEDEX 13
                          Paris, Manuela Bonmarchand (142)161-088
                          Recruiting 000816.
OTHER                     Hosp Clinic C/Villarroel / 170 Barcelona,
                          Jose Blanco (932)275-430 Recruiting 000816.

72
UNIQUE IDENTIFIER         FDA/01309
PROTOCOL ID NUMBERS       FDA 298C
PROTOCOL TITLE            A Randomized, Double-Blind, Equivalence Trial
                          Comparing Emtricitabine to Stavudine within a
                          Triple Drug Combination Containing Didanosine
                          Plus Efavirenz in Antiretroviral-Drug Naive
                          HIV-1 Infected Patients.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To assess the safety and efficacy of
                          emtricitabine as compared to stavudine when
                          used within a background regimen containing
                          another NRTI (didanosine) and an NNRTI
                          (efavirenz).
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010613)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug efficacy, Drug
                          safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 63
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: FTC-301
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method; Random
                          Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Plasma HIV-1 RNA loads greater than
                          or equal to 5,000 copies/ml at the time of
                          screening. 2. Ability to be contacted by
                          telephone by the investigator.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: Men: >= 9.1 g/dl. Women: >= 8.9
                          g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 cells/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: No restriction.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.6 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase <= 1.5 x ULN (total
                          amylase). Both lipase and pancreatic amylase
                          must be <= 1.5 times the ULN if total amylase
                          is > 1.5 times the ULN. Patients with a prior
                          history of clinical or biological
                          pancreatitis are not eligible regardless of
                          their serum amylase levels.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: PCP
                          prophylaxis (TMP/SMX, nebulized pentamidine,
                          and atovaquone).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Opportunistic infections and cancers
                          (Mycobacterium avium complex,
                          cytomegalovirus, toxoplasmic encephalitis or
                          disseminated toxoplasmosis,
                          cryptosporidiosis, Isospora belli,
                          progressive multifocal leukoencephalopathy,
                          visceral Kaposi's sarcoma, and lymphoma).
                          Patients with past episode of pulmonary
                          tuberculosis, Pneumocystis carinii pneumonia,
                          or isolated cutaneous Kaposi's sarcoma are
                          allowed. 2. AIDS-defining opportunistic
                          infection except for pulmonary tuberculosis
                          or gastrointestinal infection. 3. Acute and
                          serious medical event within 30 days of
                          screening. Acute treatment must have been
                          completed for 14 days prior to study entry.
                          4. Malabsorption or severe chronic diarrhea
                          (of Grade 2 or higher) within 30 days before
                          entry. 5. Psychosis. 6. Peripheral neuropathy
                          of Grade 3 or higher. 7. Clinical or
                          biological pancreatitis.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current alcohol or
                          illicit drug use that, in the opinion of the
                          principal investigator, may interfere with
                          the patient's ability to comply with the
                          dosing schedule and protocol evaluations.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Antiretroviral
                          drugs. Patient must have less than 3
                          cumulative days on any antiretroviral drug
                          therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Treatment
                          for acute or serious medical event. Treatment
                          must have been completed for 14 days prior to
                          study entry. 2. Treatment for tuberculosis.
                          3. Astemizole, cisapride, midazolam,
                          triazolam, ergot derivatives, St. John's
                          wort, clarithromycin, antineoplastic drugs,
                          interferon, foscarnet, cidofovir, ganciclovir
                          (intravenous or oral), rifampin, and dapsone.
                          4. Antipsychotic drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Active peripheral
                          neuropathy of Grade 2 or higher. 2.
                          Malabsorption or severe chronic diarrhea (of
                          Grade 2 or higher) or inability to consume
                          adequate oral intake (defined as the
                          inability to eat 1 or more meals a day)
                          because of chronic nausea, emesis, or
                          abdominal or esophageal discomfort.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0208  Emtricitabine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0269  Efavirenz
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
SUPPORTING AGENCY         Triangle Pharmaceuticals Inc.
LAST REVISION DATE        20010613
ALABAMA                   Univ of Alabama at Birmingham 908 20th St
                          South / 1917 Clinic Birmingham, AL 352942050
                          Glenda Black [phone] Recruiting 001122.
CALIFORNIA                St Lukes Medical Group 1855 First Ave San
                          Diego, CA 92101 Rebecca Gonzalez
                          [phone] Recruiting 000823.
CALIFORNIA                Robert Smith Medical Group 2850 6th Ave 5th
                          Floor / Suite 502 San Diego, CA 92103 Carolyn
                          Sircle [phone] Recruiting 001122.
CALIFORNIA                Saint Francis Mem Hosp / HIV Care 900 Hyde St
                          San Francisco, CA 94109 Mark Bowers
                          [phone] Recruiting 010405.
CALIFORNIA                Mem Med Group Inc 2699 Atlantic Ave Long
                          Beach, CA 90806 Debbie Mendoza [phone]
                          Recruiting 010614.
CALIFORNIA                East Bay Clinical Trial Ctr 2700 Grant St /
                          Suite 200 Concord, CA 94520 Judy Harbison
                          [phone] Recruiting 001122.
CALIFORNIA                Davies Med Ctr 45 Castro St / Suite 415 San
                          Francisco, CA 94114 John Kopchak
                          [phone] Recruiting 001127.
CALIFORNIA                Orange Coast Med Group 361 Hosp Rd Suite 126
                          Newport Beach, CA 92663 Charles Walworth
                          [phone] Recruiting 000823.
CALIFORNIA                East Bay AIDS Ctr 2850 Telegraph Ave
                          Berkeley, CA 94705 Lucinda Hopewell
                          [phone] Recruiting 001122.
CALIFORNIA                AIDS Healthcare Foundation 1300 North Vermont
                          Ave Los Angeles, CA 90027 Rubin Vidales
                          [phone] Recruiting 001122.
COLORADO                  Univ of Colorado Health Ctr / Denver Gen Hosp
                          4200 East 9th Ave Denver, CO 80262 Kristin
                          Doherty [phone] Recruiting 751101.
COLORADO                  Beacon Clinic / Boulder Community Hosp 1155
                          Alpine St Boulder, CO 80304 Anil Modak
                          [phone] Recruiting 001127.
CONNECTICUT               Blick Med Associates 589 Bedford St Stamford,
                          CT 06901 Trish Garton [phone]
                          Recruiting 001122.
DISTRICT OF COLUMBIA      George Washington Univ Med Ctr 2150
                          Pennsylvania Ave NW Washington, DC 20037
                          Suzanne Schuck [phone] Recruiting
                          001127.
DISTRICT OF COLUMBIA      Physicans Home Service 2311 M Street NW /
                          Suite 401 Washington, DC 20037 Alex Seymour
                          [phone] Recruiting 001122.
FLORIDA                   Hillsborough County Health Department 1105 E
                          Kennedy Ave / Specialty Care Center Tampa, FL
                          33602 Kathleen Mason [phone] Recruiting
                          010614.
FLORIDA                   Infectious Diseases Associates 1425 South
                          Osprey Ave Sarasota, FL 34239 Pat Carr
                          [phone] Recruiting 000823.
FLORIDA                   Health Positive 3135 State Road 580 Safety
                          Harbor, FL 34695 Beverly Wilson [phone]
                          Recruiting 001122.
FLORIDA                   Infectious Disease Research Inst 4620 N
                          Habana Ave Tampa, FL 33614 Kalliope Halkias
                          [phone] Recruiting 001122.
FLORIDA                   Gary Richmond MD 315 Southeast 14th St Fort
                          Lauderdale, FL 33316 Vernon Appleby
                          [phone] Recruiting 000823.
FLORIDA                   South Miami Hosp 7000 Southwest 62nd Ave /
                          Suite 650 Miami, FL 33143 Leon Aquino
                          [phone] Recruiting 010614.
FLORIDA                   Wohlfeiler Piperator & King MD PA 1680
                          Meridian Ave / Suite 200 Miami Beach, FL
                          33139 Irene Trujillo [phone] Recruiting
                          001122.
FLORIDA                   Larry Bush National Research Associates /
                          3175 S Congress Ave / #103 Palm Springs, FL
                          33461 Jennifer Burke [phone] Recruiting
                          000824.
GEORGIA                   Infectious Disease Specialists of Atlanta
                          2665 N Decatur Rd / Suite 330 Decatur, GA
                          30033 Katie McClure [phone] Recruiting
                          000823.
GEORGIA                   Ingenix Kern McNeill Decatur 35 Collier Rd
                          Atlanta, GA 30309 Theresa McGhee
                          [phone] Recruiting 001127.
GEORGIA                   Harbin Clinic 1825 Martha Berry Blvd Rome, GA
                          30165 Sharon Vaughan [phone] Recruiting
                          010614.
ILLINOIS                  Northstar Med Clinic 2835 North Sheffield Ave
                          Chicago, IL 60657 Harriett Wittert
                          [phone] Recruiting 000823.
LOUISIANA                 Tulane Univ Med Ctr / Infectious Diseases
                          Sect 1430 Tulane Ave New Orleans, LA 70112
                          Kathleen Brumfield [phone] Recruiting
                          010614.
MASSACHUSETTS             New England Med Ctr 750 Washington St Boston,
                          MA 02111 Betsy Adams [phone] Recruiting
                          010614.
MASSACHUSETTS             Fenway Community Health Ctr 7 Haviland St
                          Boston, MA 02115 Linda Pitler [phone]
                          Recruiting 010614.
MARYLAND                  Institute of Human Virology 725 W Lombard St
                          Baltimore, MD 21201 Sandy Zaremba
                          [phone] Recruiting 010614.
MINNESOTA                 Abbott-Northwestern Hosp / Clinic 42 2545
                          Chicago Ave South Minneapolis, MN 55404 Joann
                          Armstrong [phone] Recruiting 001122.
NEW JERSEY                South Jersey Infectious Diseases Inc 732
                          Shore Rd Somers Point, NJ 08244 Sherry
                          Jurasinski [phone] Recruiting 000823.
NEW YORK                  Mount Sinai School of Medicine One Gustave
                          Levy Place New York, NY 10029 Dilcia Ortega
                          [phone] Recruiting 001122.
NEW YORK                  Liberty Medical / Cabrini Hospital / Dept of
                          Infec Diseases 232 East 20th St / 2nd floor
                          New York, NY 10003 Rose Turelli [phone]
                          Recruiting 000823.
NEW YORK                  Dr Lawrence Fontana 117 East 18th St / First
                          Floor New York, NY 10003 Gary Wenc
                          [phone] Recruiting 001127.
NEW YORK                  Howard Grossman 155 West 19 St / 4th Floor
                          New York, NY 10011 Gervais Frechette
                          [phone] Recruiting 001127.
NEW YORK                  North Shore Univ Hosp / Div of Infectious
                          Diseases 300 Community Dr Manhasset, NY 11030
                          Pam O'Byrne [phone] Recruiting 001122.
NEW YORK                  Erie County Med Ctr 462 Grider St Buffalo, NY
                          14215 Brenda Stamos [phone] Recruiting
                          001122.
NEW YORK                  Albert Einstein College of Medicine 1300
                          Morris Park Ave Bronx, NY 10461 Gayle Kreinik
                          [phone] Recruiting 010614.
OREGON                    Fanno Creek Clinic 2400 SW Vermont St
                          Portland, OR 97219 Michael Schillen
                          [phone] Recruiting 000823.
OTHER                     Hospital Interzonal Gen de Agudos Oscar
                          Alende Juan B Justo Mar del Plata, Jorge
                          Corral (54 )223-4770296 Recruiting 010614.
OTHER                     Fundacion HUES Angel Pelutto 3932 1202 Buenos
                          Aires, Pedro Cahn [phone] Recruiting
                          000823.
OTHER                     Hospital de Agudos JM Ramos Mejia Urquiza 609
                          Sector G / Departmento de Inmunocomprometidos
                          / 122Capital Federal Buenos Aires, Marcelo
                          Losso [phone] Recruiting 000823.
OTHER                     Instituto Nacional de la Nutricion Salvador
                          Zubiran (INNSZ) / Vasco de Quiroga #15 Mexico
                          City, Sandro Nino (52 )5 6-559675 Recruiting
                          001122.
OTHER                     Fundacion Arriaran Santa Elvira 629 Santiago
                          de Chile Santiago, Claudia Abarca (56 )2
                          5-561367 Recruiting 000823.
OTHER                     FUNCEI French 3085 Buenos Aires, Isabel
                          Cassetti (114)480-30720 Recruiting 000823.
OTHER                     Hospital Muniz Uspallata 2272 / Consultorios
                          Externos Buenos Aires, Horacio Mingrone (54
                          )11 -43048704 Recruiting 001122.
OTHER                     Viridae Clinical Sciences / University of
                          British Columbia 1134 Burrard Street
                          Vancouver, BC Giovanni Boucher ( 60)4 6-47
                          4424 Recruiting 001122.
OTHER                     McMaster Univ Med Centre 1200 Main St West /
                          Rm 2F41 Hamilton, ON Lynn Kelleher
                          [phone] Recruiting 001122.
OTHER                     San Juan Veterans Administration Med Ctr 10
                          Casia St San Juan, PR 009275800 Zyndia
                          Pomales [phone] Recruiting 010614.
OTHER                     Montreal Gen Hosp 1650 Cedar Ave Montreal, QC
                          James Vatistas [phone] Recruiting
                          010614.
OTHER                     Centre De Recherche En Infectiologie 2705
                          Boul Laurier Ste-Foy , QC Lyne LaPointe
                          [phone] Recruiting 010614.
RHODE ISLAND              Paragon Clinical Research 1150 Resovoir Ave /
                          Suite 103 Cranston, RI 02920 Irene Dupont
                          [phone] Recruiting 001122.
SOUTH CAROLINA            Coastal Carolina Research Ctr 266 West
                          Coleman Blvd Mount Pleasant, SC 29464
                          Kathleen C Fletcher [phone] Recruiting
                          001122.
TEXAS                     Walter Gaman 1110 Cottonwood Lane / Suite 200
                          Irving, TX 75038 Andy Longoria [phone]
                          Recruiting 000829.
TEXAS                     Houston Clinical Research Network 215
                          Westheimer Houston, TX 77006 Jesse Rios
                          [phone] Recruiting 001122.
TEXAS                     Central Texas Clinical Research 1015 East
                          32nd Street / Suite 215 Austin, TX 78705
                          Peggy Wright [phone] Recruiting 001122.
TEXAS                     Nelson Tebedo Health Resource Ctr 4012 Cedar
                          Springs Dallas, TX 75219 Jimmy Garza
                          [phone] Recruiting 001127.
TEXAS                     Univ TX Galveston Med Branch 301 University
                          Blvd Galveston, TX 77555 Cheryl Coufal
                          [phone] Recruiting 001122.
TEXAS                     Diversified Med Practices PA 4126 Southwest
                          Freeway Houston, TX 77027 Barbara Knight
                          [phone] Recruiting 001127.
TEXAS                     Amelia Ct Clinic 1936 Amelia Ct Dallas, TX
                          75235 Tianna Peterson [phone]
                          Recruiting 001122.
WASHINGTON                Swedish Med Ctr / Dr Peter Shalit 1120 Cherry
                          St Seattle, WA 98104 Janice Price
                          [phone] Recruiting 010614.

73
UNIQUE IDENTIFIER         NIH/01296
PROTOCOL ID NUMBERS       NIAID ACTG A5024
PROTOCOL TITLE            A Phase II, Randomized, Partially Blinded
                          Trial of Combinations of Potent
                          Antiretroviral Therapy, HIV-Specific
                          Immunizations, and Cycles of Interleukin-2 to
                          Promote Efficient Control of Viral
                          Replication.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Therapeutic AIDS Vaccine
GENERAL DESCRIPTION       PURPOSE: To determine whether the addition of
                          interleukin-2 (IL-2) cycles and/or
                          HIV-specific immunizations to potent
                          antiretroviral therapy, compared with
                          receiving potent antiretroviral therapy
                          alone, results in more efficient immune
                          control of viral replication during an
                          interruption in potent antiretroviral therapy
                          by comparing the median absolute viral load
                          for each arm (average of 2 values obtained 5
                          to 6 weeks following interruption of potent
                          antiretroviral therapy). To determine the
                          safety and tolerability of administering IL-2
                          and/or HIV-specific vaccinations in
                          combination with potent antiretroviral
                          therapy regimens to HIV-infected patients for
                          1 year. To determine the safety and
                          tolerability of interrupting potent
                          antiretroviral therapy for a minimum of 6
                          weeks following greater than 18 months of
                          plasma viral load suppression with or without
                          the addition of T-cell activation treatment
                          strategies.
GENERAL DESCRIPTION       RATIONALE: The most important goal for
                          designing future therapeutic interventions is
                          to understand the nature of persistent HIV
                          infection in patients successfully treated
                          with potent antiretroviral therapy and to
                          develop strategies to promote the clearance
                          of these reservoirs or at least long-term
                          suppression of these reservoirs. If latently
                          infected cells are able to persist for a long
                          period (despite effective suppression of de
                          novo infection) primarily because immune
                          clearance is not being adequately stimulated
                          by viral antigen, then HIV-specific
                          immunization is a reasonable strategy to
                          enhance the clearance of these cells.
                          Stimulating effective HIV-specific cellular
                          immune responses at a time when plasma
                          viremia is maximally suppressed also may
                          contribute to the long-term containment of
                          HIV replication on potent antiretroviral
                          therapy. A second component to be evaluated
                          in this trial is whether broad, cyclical
                          activation of T cells with IL-2 will increase
                          the activation of HIV proviral gene
                          expression and thereby render target cells
                          susceptible to immune-mediated clearance.
                          This pathogenesis-based clinical trial will
                          explore the potential for these novel
                          treatment strategies (HIV-specific
                          immunization and IL-2, alone and in
                          combination) to complement the effects of
                          potent antiretroviral therapy by promoting
                          more effective immunologic control of HIV-1
                          replication.
GENERAL DESCRIPTION       METHODOLOGY: This study is divided into 3
                          steps. STEP I: Patients continue to receive
                          their potent antiretroviral therapy and are
                          randomized to 1 of 4 arms: Arm A: Vaccine
                          placebo; Arm B: Canarypox HIV-specific
                          immunogen (vCP1452); Arm C: 8-week cycles of
                          IL-2 plus vaccine placebo; Arm D: 8-week
                          cycles of IL-2 plus canarypox HIV-specific
                          immunogen (vCP1452). Patients receive vaccine
                          (or vaccine placebo) injections at Weeks 0,
                          8, 16, 24, and 48. IL-2 injections are
                          synchronized with vaccine injections. IL-2 is
                          given open-label while vCP1452 is
                          double-blinded. Patients must be on Step I
                          for a minimum of 51 weeks. STEP II: Patients
                          stop study medications and interrupt potent
                          antiretroviral therapy for 6 to 16 weeks.
                          Patients whose viral load during Step II
                          remains below 5,000 copies/ml are encouraged
                          to remain off antiretroviral medications and
                          continue viral-load monitoring for up to an
                          additional 10 weeks. These patients are
                          followed for up to 16 weeks on Step II and do
                          not register to Step III unless their viral
                          load increases to above 5,000 copies/ml,
                          their CD4 count decreases to below 200
                          cells/mm3, or approval is received from the
                          Protocol Chair/ Vice-Chair to join a
                          roll-over study. STEP III: Patients resume
                          their original potent antiretroviral therapy
                          regimen for 6 to 10 weeks and are monitored
                          for a minimum of 6 weeks. If patients do not
                          achieve a viral load below 50 copies/ml
                          during those 6 weeks, they continue to be
                          monitored for up to an additional 4 weeks
                          until this degree of suppression is achieved
                          with the same potent antiretroviral therapy
                          regimen or another appropriate regimen.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Immunotherapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients. 25 patients
                          per arm.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 64 to 77 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 46/100 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 27
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (000504)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5024
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Open Label;
                          Placebo-Controlled Trial; Random Allocation;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Prior or current documentation of
                          HIV-1 seropositivity by any licensed ELISA
                          test kit and confirmed at any time before
                          study entry by either Western blot, HIV-1
                          culture, HIV-1 antigen, or a second antibody
                          test by a method other than ELISA. 2. Plasma
                          HIV-1 RNA suppressed to below 50 copies/ml on
                          2 consecutive occasions (screening and
                          pre-entry) at least 7 days apart within 45
                          days of study entry using the UltraSensitive
                          Roche Amplicor HIV-1 Monitor. Documentation
                          of a previous test within 45 days of study
                          entry is acceptable for the screening value.
                          3. CD4 cell count of at least 350 cells/mm3
                          documented within 45 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.1 g/dl for men and >= 8.9
                          g/dl for women within 45 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3 Within 45 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 350 cells/mm3 Within
                          45 days prior to study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN Within 45 days prior
                          to study entry. Unless due to elevated
                          indirect bilirubin obtained in a patient
                          receiving indinavir and in the absence of
                          other evidence of significant liver disease.
                          ULN (Upper Lim
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 45 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN Within 45 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80 Within 45 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception during the study and for 90
                          days after Not breast-feeding Not pregnant
                          Negative pregnancy test within 21 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable initial
                          potent antiretroviral therapy, defined as 3
                          or more antiretroviral drugs in combination,
                          for greater than 6 months consecutively prior
                          to study entry or a change of 1 drug to
                          another drug in the same class within the
                          potent antiretroviral therapy regimen during
                          this time frame due to toxicity but not due
                          to virologic failure.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. Systemic
                          corticosteroids. If patients require daily
                          oral or IV corticosteroids for a limited time
                          for any reason, the protocol chair or vice
                          chair should be contacted to discuss whether
                          the patient should continue to participate in
                          the study. 2. Topical corticosteroids
                          provided they are applied to a site separate
                          from any skin test or IL-2 injection site.
                          For patients who require frequent topical
                          therapy to a large surface area of the body,
                          the protocol chair or vice chair should be
                          contacted to discuss whether the patient
                          should continue to participate in the study.
                          3. Maintenance therapy for opportunistic
                          infections that develop while on study
                          treatment is permitted according to standard
                          medical care, except for foscarnet during
                          IL-2 administration, and rifabutin and
                          rifampin at any time. 4. Maintenance therapy
                          for recurrent genital herpes with no more
                          than 1,000 mg/day of acyclovir. 5.
                          Erythropoietin and filgrastim (G-CSF) when
                          clinically indicated. 6. All antibiotics for
                          bacterial infections as clinically indicated.
                          7. Medications for symptomatic treatment such
                          as antipyretics and analgesics. Ibuprofen and
                          acetaminophen are the preferred agents. 8.
                          Any elective standard immunization(s) (i.e.,
                          flu shot) should be given no less than 4
                          weeks prior to any blood draw for HIV RNA
                          assay.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Any AIDS-defining illness by the CDC case
                          definition with the exception of cutaneous
                          Kaposi's sarcoma. Patients with minimal
                          Kaposi's sarcoma, defined as fewer than 5
                          cutaneous lesions and no visceral disease or
                          tumor-associated edema, will be allowed to
                          enroll as long as they do not require
                          systemic therapy for Kaposi's sarcoma. 2.
                          Documentation of virologic failure (defined
                          as above 10,000 copies/ml) while actively
                          receiving protease inhibitors or any 3-drug
                          potent antiretroviral therapy regimen at any
                          time prior to study entry and not due to
                          interruption of potent antiretroviral
                          therapy, toxicity, drug availability, or
                          temporary illness. (Prior to study entry, if
                          documentation of plasma HIV RNA above 10,000
                          copies/ml is obtained and occurred during an
                          interruption in antiretroviral therapy [i.e.,
                          adverse effects or a temporary illness] and
                          then subsequent HIV RNA viral load
                          suppression was again achieved on the same or
                          an altered regimen, then this HIV RNA value
                          will not be interpreted as a sign of
                          virologic failure on the previous regimen.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          substance abuse that, in the opinion of the
                          investigator, will seriously compromise the
                          patient's ability to adhere with the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any elective
                          standard immunization(s) (i.e., flu shot)
                          within 4 weeks prior to any blood draw for
                          HIV RNA assay. 2. Immunomodulatory therapy
                          within 4 weeks prior to study entry including
                          but not limited to drugs such as systemic
                          corticosteroids, interferons, interleukins,
                          thalidomide, sargramostim (GM-CSF),
                          dinitrochlorobenzene (DNCB), thymosin alpha,
                          thymopentin, inosiplex, polyribonucleoside,
                          ditiocarb sodium. 3. Systemic treatment with
                          IL-2 at any time before study entry. 4.
                          Rifampin or rifabutin within 7 days before
                          study entry if receiving indinavir. 5.
                          Therapy for active infection or significant
                          medical illness within 30 days before study
                          entry. 6. Any HIV vaccine during the past
                          year or at any time while on the present
                          antiretroviral regimen. 7. Immunizations
                          within 30 days before study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          elective standard immunization(s) (i.e., flu
                          shot) within 4 weeks prior to any blood draw
                          for HIV RNA assay. 2. Drugs that are
                          contraindicated in combination with the
                          antiretroviral agents to be taken by
                          individual patients. 3. Interferons,
                          interleukins (other than the study IL-2),
                          sargramostim, dinitrochlorobenzene, thymosin
                          alpha 1, thymopentin, inosiplex,
                          polyribonucleoside, ditiocarb sodium,
                          thalidomide, St. John's wort, systemic or
                          local cytotoxic chemotherapy for malignancy,
                          systemic corticosteroids. (Should patients
                          require daily oral or IV corticosteroids for
                          a limited time for any reason, the protocol
                          chair or vice chair should be contacted to
                          discuss whether the patient should continue
                          to participate in the study.) 4. Treatment
                          for active cardiac or vascular disease, other
                          than stable hypertension with drugs including
                          anti-anginal agents such as nitrates, beta
                          blockers, calcium channel blockers,
                          anti-arrhythmics including digitalis and
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Any AIDS-defining
                          illness by the CDC case definition with the
                          exception of cutaneous Kaposi's sarcoma.
                          Patients with minimal Kaposi's sarcoma,
                          defined as fewer than 5 cutaneous lesions and
                          no visceral disease or tumor-associated
                          edema, will be allowed to enroll as long as
                          they do not require systemic therapy for
                          Kaposi's sarcoma. 2. Significant cardiac
                          insufficiency (e.g., New York Heart
                          Association Grade 2 or greater). Patients
                          with isolated hypertension controlled by
                          antihypertensive medication but no cardiac
                          disease will be eligible for this study. 3.
                          Malignancy requiring treatment with systemic
                          or local cytotoxic chemotherapy. 4. Untreated
                          thyroid disease, with the exception of
                          treated and stable hyperthyroidism or
                          hypothyroidism for at least 4 weeks before
                          study entry.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arms B and D: 1 ml
                          at Weeks 0, 8, 16, 24, and 48. Drug 2: Arms C
                          and D: 4.5 MIU bid for 5 days every 8 weeks
                          (beginning at Week 0) for 48 weeks
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Subcutaneous
OTHER TREATMENT INFO.     END POINT: Immune control of viral
                          replication during an interruption in
                          antiretroviral therapy defined as the mean of
                          the log10 (HIV RNA copies/ml) obtained at
                          Weeks 5 and 6 following interruption of
                          potent antiretroviral therapy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients prematurely
                          discontinued after receipt of any IL-2 and/or
                          vaccine (vCP1452 or placebo) prior to Week 52
                          will be followed on-study, off treatment
                          until Week 48 (unless the patient meets
                          eligibility criteria for Step II) and then
                          discontinued from study. Patients may be
                          discontinued from the study for the following
                          reasons: 1. Patient is non-adherent with
                          study medications or clinic visits. 2.
                          Treatment-related toxicity that requires
                          permanent study treatment discontinuation and
                          patient does not meet minimum treatment
                          requirements for entry onto Step II. 3.
                          Required use of any prohibited medications.
                          4. Patient voluntarily withdraws from the
                          study for any reason. 5. Pregnancy and
                          breast-feeding. Patient will be followed for
                          safety for at least 1 month. 6. Patient
                          discontinues antiretroviral therapy for 4
                          weeks or longer on Steps I or III. 7. Patient
                          changes antiretroviral drugs without
                          consulting the site investigator (protocol
                          team should be consulted prior to
                          discontinuing patient from study). 8. CD4
                          count below 200 cells/mm3 on 2 consecutive
                          occasions on Step I only. Study
                          discontinuation will not occur until after
                          Week 48 follow-up. 9. Development of an
                          AIDS-defining illness (other than cutaneous
                          Kaposi's sarcoma, see exclusion criteria) at
                          any time on-study. 10. HIV-1 RNA levels rise
                          above 5,000 copies/ml on 2 consecutive
                          occasions during Step I (and the rise is not
                          believed to be related to transient illness
                          or temporary interruption in dosing). Patient
                          should consult the primary care physician
                          regarding a change in antiretroviral therapy
                          and be followed on-study but off study drug.
                          The patient will receive all evaluations
                          scheduled at Weeks 16 and 48. Patient will
                          not be eligible for entry to Step II and
                          should be permanently discontinued from the
                          study after completion of the Week 48
                          evaluations.
OTHER TREATMENT INFO.     MODIFICATION: IL-2 may be permanently
                          discontinued or interrupted due to
                          unacceptable toxicities as outlined in the
                          protocol. If IL-2 is interrupted, the
                          patient's next cycle will be dose-reduced.
                          However, patients who have their IL-2
                          interrupted for intolerability can have it
                          resumed at the same dose or at 1 dose-level
                          reduction. Patients who experience an
                          elevation in CD4 cell count to above 2,000
                          cells/mm3 while receiving IL-2 will receive
                          injections every 16 weeks for the duration of
                          Step I.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 000907.
CALIFORNIA                Univ of California San Francisco 3180 18th St
                          San Francisco, CA 94110 Julieann Lewis
                          [phone] Recruiting 010406.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 000907.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 000907.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 000907.
CALIFORNIA                Santa Clara Valley Med Ctr / AIDS Community
                          Rsch Consortium 751 South Bascom Ave San
                          Jose, CA 951282699 Debbie Slamowitz
                          [phone] Recruiting 000907.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 001013.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Mario Guerrerro
                          [phone] Recruiting 000907.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 001013.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 001006.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 000912.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Beth Dean [phone] Recruiting
                          010119.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          000907.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 001219.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 000907.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 000907.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 000907.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 010118.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 001129.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 001018.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 000922.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] No longer recruiting 010320.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 010207.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 001025.
PENNSYLVANIA              Philadelphia Veterans Administration Med Ctr
                          536 Johnson Pavilion Philadelphia, PA 19104
                          Christopher Helker [phone] Recruiting
                          001018.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 001025.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone]
                          Recruiting 000907.

74
UNIQUE IDENTIFIER         NIH/01292
PROTOCOL ID NUMBERS       NIAID ACTG A5015
PROTOCOL TITLE            A Phase II Exploratory Study Examining
                          Immunologic and Virologic Indices in Two
                          Age-Differentiated Cohorts of HIV-Infected
                          Subjects to Explore the Basis of Accelerated
                          HIV-Disease Progression Associated with
                          Aging.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To compare the magnitude of changes
                          in naive (CD45RA+/CD62L+) CD4+ lymphocytes
                          between 2 age-differentiated study groups
                          after 48 weeks of study treatment.
GENERAL DESCRIPTION       RATIONALE: Older age is an important risk
                          factor for accelerated HIV-disease
                          progression. However, the virologic response
                          to highly active antiretroviral therapy
                          (HAART) may be superior in older persons. A
                          better understanding of the immunologic,
                          virologic, and behavioral mechanisms that
                          underlie these age-related differences may
                          help to elucidate critical immune responses
                          that are necessary to control the progression
                          of HIV-disease.
GENERAL DESCRIPTION       METHODOLOGY: Patients are grouped according
                          to age. Group A consists of patients between
                          the ages of 13 and 30 years. Group B consists
                          of patients age 45 years or older. All
                          patients receive open-label
                          lopinavir/ritonavir (LPV/RTV) plus
                          emtricitabine (FTC) plus stavudine (d4T) for
                          96 weeks. Study visits occur at pre-entry,
                          entry, and Weeks 4, 8, 12, 16, and 24 then
                          every 12 weeks thereafter through Week 96.
                          Clinical assessments, safety laboratory
                          tests, CD4 cell count monitoring, lymphocyte
                          phenotyping, and HIV-1 RNA determinations are
                          performed routinely. Blood samples are stored
                          for further immunology and virology studies.
                          Patients may volunteer to participate in
                          virology substudy A5020s and either
                          immunology substudy A5016s or A5017s.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients. 45 patients
                          per cohort. The majority of patients in Group
                          B (at least 23 patients) must be 50 years or
                          older. [AS PER AMENDMENT 1/19/01: T
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 96 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 89/90 010712.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 42
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010119)
PROTOCOL DETAILS          DISEASE STUDIED: HIV InfectionsS
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Cross-Sectional Study; Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have HIV-1 infection as documented by
                          licensed ELISA test and confirmed by either
                          Western blot (preferred), HIV-1 culture,
                          HIV-1 antigen, plasma HIV-1 RNA, or a second
                          antibody test other than an ELISA at any time
                          before the study. 2. Have a plasma HIV-1 RNA
                          level greater than 2,000 copies/ml by Roche
                          Amplicor HIV Monitor assay (Standard or
                          Ultrasensitive) performed by an
                          AACTG/NIAID-certified or Roche-certified
                          virology laboratory no more than 60 days
                          before study entry. 3. Have a CD4 count
                          between 100 and 600 cells/mm3 [AS PER
                          AMENDMENT 1/19/01: CD4 count less than 600
                          cells/mm3] performed at an
                          AACTG/NIAID-certified laboratory no more than
                          60 days before study entry. 4. Be between the
                          ages of 13 and 30 years (need consent of
                          parent or guardian if under 18), or be 45 or
                          more years of age at study entry. [AS PER
                          AMENDMENT 1/19/01: The first 50 patients
                          accrued for this study must be co-enrolled in
                          the immunology substudy ACTG A5016s or ACTG
                          A5017s.].
PATIENT INCLUSION CRIT.   HEMOGLOBIN: 9.1 or greater g/dl for men and
                          8.9 or greater g/dl for women. No more than
                          21 days before study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 No more than 21
                          days before study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 100 to 600 cells/mm3 No
                          more than 60 days before study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN ULN (Upper Limit of
                          Normal). No more than 21 days before study
                          entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN No more than 21 days
                          before study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN No more than 21 days
                          before study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN No more than 21 days
                          before study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70 No more than 21 days before
                          study entry.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase <= 1.5 x ULN. If serum
                          amylase > 1.5 x ULN, pancreatic amylase must
                          be <= 1.5 x ULN. No more than 21 days before
                          study entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Not pregnant
                          Negative pregnancy test within 21 days prior
                          to study entry.
PATIENT INCLUSION CRIT.   RISK BEHAVIOR: Allowed with caution:
                          Alcoholic beverages.
PATIENT INCLUSION CRIT.   OTHER: The main study has been approved for
                          prisoner participation.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: Alternative
                          therapies such as acupuncture and
                          visualization techniques.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: Up to 14 days
                          therapy with any antiretroviral drug.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis or maintenance treatment of
                          opportunistic infections with approved agents
                          (unless excluded elsewhere) as clinically
                          indicated including chemoprophylaxis for PCP,
                          which should be administered to all patients
                          who have a CD4 cell count of less than 200
                          cells/mm3. 2. Topical and oral antifungal
                          agents as clinically indicated, unless
                          excluded elsewhere. 3. Antibiotics as
                          clinically indicated, unless excluded
                          elsewhere. 4. Required medications such as
                          antipyretics, analgesics, antiemetics,
                          antimotility agents, allergy medications,
                          antidepressants, sleep medications, oral
                          contraceptives, megestrol acetate,
                          testosterone, etc., as clinically indicated,
                          unless excluded elsewhere. 5. Alternative
                          antiretroviral therapy with investigational
                          or FDA-approved nucleoside analogue reverse
                          transcriptase inhibitor(s), nonnucleoside
                          reverse transcriptase inhibitor(s), and/or
                          protease inhibitors for patients who must
                          discontinue study medications because of
                          toxicities and/or virologic failure upon
                          consultation and per approval of the protocol
                          chair(s). Alternative antiretroviral agents
                          will not be provided by this study. 6.
                          Patients experiencing hyperlipidemia may be
                          candidates for lipid-lowering agents. 7. Oral
                          contraceptives or depoprogesterone; must not
                          be used as the sole form of birth control for
                          women of reproduction potential because it is
                          unknown whether the combination of study
                          medications can alter the effectiveness of
                          oral contraceptives or depoprogesterone. Due
                          to the lack of well-controlled studies of the
                          study-assigned treatment regimen during
                          pregnancy, all patients enrolled in the study
                          must use effective forms of birth control for
                          the duration of this study. 8. Systemic
                          corticosteroid use for less than 21 days, for
                          acute conditions (e.g., thrombocytopenia,
                          obstructive pulmonary disease, moderate to
                          severe PCP) as clinically indicated. Steroid
                          use for more than 21 days will be considered
                          by the protocol chair(s) on a case-by-case
                          basis. 9. Recombinant erythropoietin (rE
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Documented or suspected acute hepatitis
                          within 30 days of study entry. 2. Chronic
                          diarrhea defined as more than 3 liquid stools
                          per day for more than 14 days within 30 days
                          of study entry. 3. Serious infection or other
                          serious medical illness that is potentially
                          life threatening and requires systemic
                          therapy and/or hospitalization within 14 days
                          prior to study entry. Patients with
                          Pneumocystis carinii pneumonia (PCP) must
                          have completed acute therapy at least 14 days
                          prior to study entry and be clinically
                          stable. Patients with other serious infection
                          or medical illness who must continue with
                          chronic (maintenance) therapy, such as for
                          disseminated Mycobacterium avium complex
                          (MAC) or sinusitis, must have completed at
                          least 14 days of therapy before entering the
                          study and be clinically stable, with the
                          exception of oral and vaginal candidiasis,
                          mucocutaneous herpes simplex infection, and
                          minor skin conditions which have no
                          restriction.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 21 days of
                          the study entry: Radiation.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than 14
                          days therapy with any antiretroviral drug. 2.
                          Interferons, interleukins, or HIV vaccines
                          within 30 days of study entry. 3.
                          Erythropoietin, G-CSF, GM-CSF, or growth
                          hormone within 30 days of study entry. 4. Any
                          investigational agents within 30 days of
                          study entry, unless allowed otherwise in
                          writing by the protocol chair. Excluded
                          within 21 days of study entry: 1. Systemic
                          corticosteroid use for chronic conditions and
                          anabolic steroid use, unless within
                          physiological replacement levels and upon the
                          consultation and written approval of the
                          protocol chair(s). 2. Any alternative
                          antiretroviral therapies for which the
                          selection was not approved in writing by the
                          protocol chair(s). 3. Any investigational
                          agents without specific written approval of
                          the protocol chair(s). 4. Systemic cytotoxic
                          chemotherapy. 5. Any immunomodulator that
                          affects immunologic or virologic indices
                          including, but not limited to, thalidomide,
                          interleukins, interferons, or ot
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          corticosteroid use for chronic conditions and
                          anabolic steroid use, unless within
                          physiological replacement levels and upon the
                          consultation and written approval of the
                          protocol chair(s). 2. Any alternative
                          antiretroviral therapies for which the
                          selection was not approved in writing by the
                          protocol chair(s). 3. Any investigational
                          agents without specific written approval of
                          the protocol chair(s). 4. Systemic cytotoxic
                          chemotherapy. 5. Any immunomodulator that
                          affects immunologic or virologic indices
                          including, but not limited to, thalidomide,
                          interleukins, interferons, or other
                          cytokines. 6. Amiodarone, astemizole,
                          cisapride, ergot alkaloids and derivatives,
                          Hypericum perforatum (St. John's Wort),
                          lovastatin, midazolam, propoxyphene,
                          quinidine, rifampin, simvastatin,
                          terfenadine, triazolam, and [AS PER AMENDMENT
                          1/19/01: flecainide, pimozide, and
                          propafenone].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. AIDS-related
                          malignancy requiring systemic chemotherapy,
                          with the exception of minimal Kaposi's
                          sarcoma, which is defined as 5 or fewer
                          cutaneous lesions, no visceral disease or no
                          tumor-associated edema, and no systemic
                          chemotherapy required. 2. Any medical
                          condition that, in the opinion of the
                          investigator, would interfere with the
                          patient's ability to participate in or adhere
                          to the requirements of the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0208  Emtricitabine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0316  Lopinavir/Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 30 mg bid (weight <
                          60 kg). 40 mg bid (weight >= 60 kg). Drug 2:
                          200 mg qd. Drug 3: Lopinavir 400 mg/ritonavir
                          100 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 60 mg (weight < 60 kg).
                          80 mg (weight >= 60 kg). Drug 2: 200 mg. Drug
                          3: Lopinavir 800 mg/ritonavir 200 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 96 weeks.
OTHER TREATMENT INFO.     END POINT: Absolute naive (CD45RA+/CD62L+)
                          CD4+ lymphocyte count at the Week 48
                          evaluation minus the arithmetic mean of the
                          absolute counts at entry and pre-entry
                          evaluations (i.e., CD45RA+/CD62L+/ CD4+ count
                          at Week 48 minus the arithmetic mean of the
                          entry and pre-entry value).
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Request by the
                          patient or legal guardian. 2. Determination
                          by the local investigator or primary care
                          physician that continued participation, or
                          patient's failure to adhere to study
                          requirements, would be detrimental to the
                          patient's health, well-being, or the validity
                          of study results. 3. Development of an
                          exclusionary condition [AS PER AMENDMENT
                          1/19/01: with the exception of pregnancy]. 4.
                          Selection of alternative antiretroviral
                          agents not approved in writing by the study
                          chair(s). 5. Development of study drug
                          toxicities requiring discontinuation or
                          required treatment with medications that are
                          disallowed while on this study. 6. Women who
                          become pregnant and do not wish to be
                          followed according to requirements outlined
                          in the protocol. [AS PER AMENDMENT
                          1/19/01:Women who become pregnant and wish to
                          continue on study may do so as long as they
                          discontinue FTC and d4T and do not
                          breast-feed.] 7. Generalized debilitation or
                          transfer to nursing home, hospice, or
                          alternative care such that administration of
                          study treatment and/or follow-up is no longer
                          possible. 8. The study is canceled by the
                          Food and Drug Administration (FDA), the
                          National Institute of Allergy and Infectious
                          Diseases (NIAID), the Adult ACTG, or the
                          pharmaceutical companies supplying study
                          treatment.
OTHER TREATMENT INFO.     MODIFICATION: All study medications are
                          interrupted when indicated for
                          medication-related toxicity as outlined in
                          the protocol. A dose modification of d4T is
                          allowed for peripheral neuropathy as outlined
                          in the protocol. Dose modifications of other
                          study medications are not allowed, except
                          upon consultation with the study chair(s). If
                          required, only one level of dose reduction
                          for d4T is allowed. There is no dose
                          reduction for LPV/RTV or FTC.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Marin County Specialty Clinic 161 Mitchell
                          Building Suite 200 San Rafael, CA 94903 Marc
                          Gould [phone] Recruiting 001017.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] No longer recruiting 010501.
CALIFORNIA                Santa Clara Valley Med Ctr / AIDS Community
                          Rsch Consortium 751 South Bascom Ave San
                          Jose, CA 951282699 Debbie Slamowitz
                          [phone] Recruiting 001017.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 001017.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          001017.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone] No
                          longer recruiting 010501.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone] No
                          longer recruiting 010501.
COLORADO                  Denver Dept of Health and Hosps 4200 East 9th
                          Ave / Campus Box B-196 Denver, CO 80262 M
                          Graham Ray [phone] Recruiting 001017.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 001017.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 001017.
HAWAII                    Queens Med Ctr Leahi Hospital / Young
                          Building / 3675 Kilauea Ave Honolulu, HI
                          96816 Debra Ogata-Arakaki [phone]
                          Recruiting 001024.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          001017.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 001024.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 001017.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 010118.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 010118.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 010118.
MASSACHUSETTS             Brigham and Women's Hosp Div of Infectious
                          Diseases / 15 Francis St PBB A-4 Boston, MA
                          02215 Carolyn Koziol [phone] Recruiting
                          001017.
MASSACHUSETTS             Harvard (Massachusetts Gen Hosp) 55 Fruit St
                          / Founders Bldg 8th Floor Boston, MA 02114
                          Teri Flynn [phone] Recruiting 001017.
MASSACHUSETTS             Boston Med Ctr 1 Boston Med Ctr Place /
                          Dowling Bldg Boston, MA 02118 Beth Hankin
                          [phone] Recruiting 001025.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Denise Wright
                          [phone] Recruiting 010723.
MARYLAND                  State of MD Div of Corrections / Johns
                          Hopkins Univ Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 212052196 Denise
                          Wright [phone] Recruiting 001017.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 010205.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 001017.
NORTH CAROLINA            Carolinas Med Ctr PO Box 32861 Charlotte, NC
                          28232 Sharon Hewat [phone] Recruiting
                          010118.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Cheryl
                          Marcus [phone] Recruiting 001019.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone] No
                          longer recruiting 010213.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] No longer recruiting 010320.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] Recruiting 001019.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 001017.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] No longer recruiting 010320.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 001017.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 001017.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 001017.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          No longer recruiting 010627.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 001025.
PENNSYLVANIA              Philadelphia Veterans Administration Med Ctr
                          536 Johnson Pavilion Philadelphia, PA 19104
                          Christopher Helker [phone] Recruiting
                          001031.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 001116.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 001017.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone]
                          Recruiting 001017.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 001017.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 001017.

75
UNIQUE IDENTIFIER         NIH/01291
PROTOCOL ID NUMBERS       NIAID ACTG P1010
PROTOCOL TITLE            Effect of Antiretroviral Therapy on Body
                          Composition in HIV-Infected Children.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To describe changes in body
                          composition in HIV-infected children at 12,
                          24, 36, and 48 weeks after, compared to
                          before, beginning or changing antiretroviral
                          therapy, and to describe age differences in
                          these changes in body composition. To
                          correlate changes in body composition with
                          changes in viral load and CD4+ cell counts in
                          HIV-infected children beginning or changing
                          antiretroviral therapy over 12-, 24-, 36-,
                          and 48-week periods. To measure cytokines in
                          HIV-infected children beginning or changing
                          antiretroviral therapy over 12-, 24-, 36-,
                          and 48-week periods and to correlate changes
                          in body composition with changes in
                          cytokines. To correlate changes in body
                          composition at 12 weeks with changes in
                          height and weight growth velocities at 24,
                          36, and 48 weeks.
GENERAL DESCRIPTION       RATIONALE: Despite accumulating data in
                          adults, little information is available
                          regarding the effects of HIV infection and
                          antiretroviral therapy on body composition in
                          children. Preliminary information indicates
                          that lean body mass is lost in preference to
                          fat mass in HIV-infected children, supporting
                          the theory that failure to thrive in HIV
                          infection is often cytokine mediated. It can
                          be hypothesized that changes in body
                          composition (lean body mass) may predict
                          changes in weight growth velocity and may
                          give an early clinical indication of
                          treatment failure. If so, body composition
                          measurement may yield an additional outcome
                          measure for clinical trials, equivalent in
                          utility to other laboratory measures of
                          treatment response, e.g., persistent CD4+
                          cell count changes. Additionally, if body
                          composition changes are highly correlated
                          with responses in viral load, body
                          composition may prove to be a more affordable
                          measure of antiretroviral effectiveness in
                          developing countries.
GENERAL DESCRIPTION       METHODOLOGY: This study is a nonrandomized,
                          observational study. Children are recruited
                          to each of 4 age strata: Stratum A: 1 month
                          to 18 months. Stratum B: greater than 18
                          months to 3 years. Stratum C: greater than 3
                          years to 8 years. Stratum D: greater than 8
                          years to less than 13 years. Children
                          beginning or changing antiretroviral therapy
                          and fulfilling the study specifications may
                          be enrolled in the study. Children have 5
                          outpatient clinic visits, at entry and at 12,
                          24, 36, and 48 weeks, for anthropometry, body
                          composition by bioelectrical impedance
                          analysis, cytokine levels, viral load, CD4+
                          cell count, and markers of lipid and glucose
                          metabolism.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Clinical Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients. 25 children
                          per age stratum.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 36/100 010731.
PROTOCOL DETAILS          STUDY DURATION: 48 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 46
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (000426)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1010
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study;
                          Nonrandomized Concurrent Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Children must
                          have: 1. Documented HIV-1 infection (defined
                          as 2 positive assays [DNA PCR, HIV culture,
                          p24 antigen detection, or licensed ELISA with
                          confirmatory Western blot] from 2 different
                          samples). 2. Reached Tanner stage 1. 3.
                          Parent or legal guardian able and willing to
                          provide signed informed consent. Allowed:
                          Afebrile upper respiratory infection.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: 1. Glucocorticoid
                          therapy, provided that treatment was not
                          taken during the 14 days prior to entry and
                          total steroid exposure in the 180 days prior
                          to entry did not exceed 15 days. 2. Protease
                          inhibitors (PIs), if child is changing
                          antiretroviral therapy due to virologic
                          indications and he/she is naive to at least 2
                          of the agents in the new therapy regimen.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Beginning or
                          changing antiretroviral therapy, with the
                          following specifications: (1)
                          antiretroviral-naive patients starting any
                          antiretroviral therapy; or (2) PI-naive
                          patients beginning a PI-containing regimen;
                          or (3) children with prior PI therapy who are
                          changing antiretroviral therapy due to
                          virologic indications and that are naive to
                          at least 2 of the agents in the new therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 01
                          months less than or equal to 12 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Children with the
                          following prior conditions are excluded:
                          Acute illness or fever in the 14 days prior
                          to entry, except afebrile upper respiratory
                          infection.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Steroids
                          (corticosteroids, anabolic steroids, or
                          megestrol acetate), interleukin, interferon,
                          thalidomide, or GH within 180 days prior to
                          entry. (Glucocorticoid therapy is allowed
                          provided that treatment was not taken during
                          the 14 days prior to entry and total steroid
                          exposure in the 180 days prior to entry did
                          not exceed 15 days.) 2. Antiretrovirals, if
                          the child is beginning any antiretroviral
                          therapy. 3. Protease inhibitors, if the child
                          is beginning a PI-containing regimen. (Prior
                          PI therapy is allowed if child is changing
                          antiretroviral therapy due to virologic
                          indications and he/she is naive to at least 2
                          of the agents in the new therapy regimen.).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Children with the following
                          symptoms or conditions are excluded: 1. Acute
                          illness or fever, except afebrile upper
                          respiratory infection. 2. Malignancy. 3. Use
                          of metal prostheses or implanted electrical
                          devices (i.e., pacemakers or automatic
                          implantable cardiac defibrillators). 4.
                          Pubertal development (Tanner stage 2 or
                          beyond). 5. Limb amputation. 6. Physical
                          disability that would prevent a reliable
                          assessment of height or length. 7.
                          Insulin-dependent diabetes.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233 Terry
                          Byars [phone] Recruiting 010318.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 001024.
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 000922.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Mary Caffery [phone]
                          Recruiting 010530.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 001019.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] Recruiting 010109.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Julie Ziegler
                          [phone] Recruiting 000726.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 000915.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 001006.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 001110.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 000824.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          000726.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 001205.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 000817.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 000914.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          001116.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Lucrecia Rios [phone]
                          Recruiting 010517.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Bishop [phone] Recruiting 000914.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 000829.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 000629.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 000801.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MARYLAND                  Univ of Maryland at Baltimore / Univ Med Ctr
                          700 W Lombard Street / 2nd Floor Baltimore,
                          MD 21201 Kara Fore [phone] Recruiting
                          010612.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 000824.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 010406.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Lisa Cerrachio
                          [phone] Recruiting 010117.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 000614.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 001024.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 010405.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 001205.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 010318.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 010406.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Shailaja Kancherla Recruiting 000824.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 000915.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 010316.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 001116.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 000922.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 000829.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          000726.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Maria del Pilar Thurin
                          [phone] Recruiting 001012.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 000922.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Anne Cope [phone] Recruiting
                          010119.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          001116.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 010115.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 010318.

76
UNIQUE IDENTIFIER         NIH/01279
PROTOCOL ID NUMBERS       NIAID CPCRA 064
PROTOCOL TITLE            A Randomized Study of a Prescribed 4-Month
                          Structured Treatment Interruption (STI)
                          Followed by Initiation of a New
                          Antiretroviral Regimen Versus Immediate
                          Initiation of a New Antiretroviral Regimen in
                          HIV-Infected Patients with Multidrug
                          Resistant (MDR) Virus.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare the long-term (minimum 24
                          months) clinical benefits and risks of a
                          4-month structured treatment interruption
                          (STI) followed by a new antiretroviral drug
                          regimen with immediately initiating a new
                          antiretroviral drug regimen.
GENERAL DESCRIPTION       RATIONALE: An increasing number of patients
                          are developing multidrug-resistant (MDR)
                          virus, as determined by genotypic
                          antiretroviral resistance testing (GART), due
                          to treatment failure to suppress viral
                          replication after several rounds of
                          combination antiretroviral therapy. The best
                          therapeutic strategy for these patients is
                          uncertain. Two strategies currently being
                          used are (1) STI followed by a new
                          antiretroviral regimen and (2) immediate
                          initiation of a new antiretroviral regimen.
GENERAL DESCRIPTION       METHODOLOGY: Patients are screened for the
                          presence of MDR virus and a plasma HIV RNA
                          level greater than 10,000 [AS PER AMENDMENT
                          7/3/01: greater than 5,000] copies/ml.
                          Eligible patients attend a baseline visit [AS
                          PER AMENDMENT 7/3/01: and a subsequent
                          randomization visit] where the qualifying
                          GART results are provided. Patients who
                          consent to participate have phenotypic
                          antiretroviral resistance testing (PART) done
                          on a specimen from the same blood draw that
                          was used for the GART evaluation. After PART
                          results are available, patients are
                          randomized [AS PER AMENDMENT 7/3/01: If the
                          predicted sensitivities are not available for
                          some or all drugs included in the PART, the
                          patient may still be randomized.] to either a
                          4-month STI followed by a new antiretroviral
                          regimen or an immediate new antiretroviral
                          regimen. The antiretroviral regimens chosen
                          are based on the patients' history and both
                          GART and PART results. [AS PER AMENDMENT
                          7/3/01: Additional GART and PART may be
                          requested after at least 4 months of
                          antiretroviral treatment.] Patients have the
                          follow-up data collection done at Months 1-8,
                          12, and every 4 months thereafter. Changes in
                          antiretroviral therapy, Grade 4 adverse
                          experiences, progression of disease, and
                          deaths are reported as they occur. Patients
                          are seen for clinical management as often as
                          deemed necessary. All patients are followed
                          to a common closing date estimated to be 24
                          months after the last patient is randomized.
                          Some patients may participate in a Point
                          Mutation Substudy [AS PER AMENDMENT 7/3/01:
                          Plasma Point Mutation Substudy and PBMC Point
                          Mutation Substudy].
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Strategy determination.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 480 patients. 240 in each
                          treatment group.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 months after
                          the last patient is randomized.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 155/480 010731.
PROTOCOL DETAILS          STUDY DURATION: 12 months [AS PER AMENDMENT
                          7/3/01: 24 months] plus 24 months fo
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010703)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Random
                          Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Evidence of MDR virus based on the
                          results of GART, performed by a
                          CPCRA-approved laboratory, from a specimen
                          [AS PER AMENDMENT 7/3/01: the following text
                          has been deleted: obtained within 45 days
                          prior to the baseline visit]. MDR virus is
                          defined as a virus with [AS PER AMENDMENT
                          7/3/01: a)] broad protease inhibitor (PI)
                          resistance combined with broad nonnucleoside
                          reverse transcriptase inhibitor (NNRTI)
                          resistance [AS PER AMENDMENT 7/3/01: or]
                          broad nucleoside reverse transcriptase
                          inhibitor (NRTI) resistance, or both [AS PER
                          AMENDMENT 7/3/01:or b) broad NNRTI resistance
                          and broad NRTI resistance and at least 1 PI
                          mutation from the broad PI mutation list].
                          Specifically, to be considered MDR, the virus
                          must have at least 2 of the following
                          mutations in the protease gene (broad PI
                          resistance): 90M, 48V, 82A/F/T, 84V, [AS PER
                          AMENDMENT 7/3/01: 50V, and] 46I/L. In
                          addition, the virus must have at least 1 of
                          the following sets of mutations in the RT
                          gene: (1) Broad NNRTI resistance - 103N, or
                          [AS PER AMENDMENT 7/3/01: 181C or at least] 2
                          of the following mutations: 101E, 106A, 108I,
                          [AS PER AMENDMENT 7/3/01:181C/I has been
                          deleted and the following added: 181I] ,
                          188C, 190A/S; (2) Broad NRTI resistance -
                          151M or 69S(XX) insertion or a combination of
                          215Y/F with at least 1 of the following
                          mutations: 184V, 74V, 65R, 69D. 2. Plasma HIV
                          RNA above 10,000 [AS PER AMENDMENT 7/3/01:
                          above 5,000] copies/ml from the same blood
                          draw as the qualifying GART specimen. 3. An
                          ophthalmologic exam prior to randomization
                          (for patients with a history of
                          cytomegalovirus [CMV] retinitis). 4. Signed
                          informed consent of parent or guardian if
                          under 18.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test within 7
                          days of study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable
                          antiretroviral regimen between 14 days prior
                          to when the patient's qualifying GART
                          specimen was obtained and randomization. For
                          the purposes of this protocol, a stable
                          antiretroviral regimen is defined as having
                          no more than one drug added to, or
                          discontinued from, the regimen. However, any
                          or all of the patient's antiretroviral drugs
                          may be temporarily discontinued for a single
                          period lasting no more than 14 days during
                          the time between when the qualifying GART
                          specimen was obtained and 15 days prior to
                          randomization.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Intention of
                          patient and clinician to initiate a new
                          antiretroviral drug regimen for the patient
                          at the protocol-designated times.
                          Recommended: 1. If primary or secondary
                          prophylaxis for Pneumocystis carinii
                          pneumonia (PCP) or Mycobacterium avium
                          complex (MAC) infection has been withdrawn
                          due to CD4 cell count rebound, it is
                          recommended that prophylaxis be resumed prior
                          to randomization. 2. Prophylaxis for
                          opportunistic infections in keeping with
                          USPHS/IDSA guidelines.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Intercurrent illness within 14 days prior to
                          the time that either the screening or
                          randomization GART specimen was obtained and
                          that, in the clinician's judgment, could
                          influence the patient's HIV RNA level.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Vaccinations
                          within 14 days prior to the time that either
                          the screening or randomization GART specimen
                          was obtained and that, in the clinician's
                          judgment, could influence the patient's HIV
                          RNA level. 2. IL-2 within 120 days prior to
                          the date when the qualifying GART specimen
                          was obtained or any use between that date and
                          randomization.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: IL-2 during
                          the 12-month period following randomization.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Active
                          opportunistic infection requiring acute
                          treatment. 2. Currently being followed in the
                          PIP study (CPCRA 057).
OTHER TREATMENT INFO.     END POINT: Clinical disease progression (as
                          defined in the CPCRA Data Collection
                          Handbook) or death.
OTHER TREATMENT INFO.     MODIFICATION: Patients assigned to the STI
                          group are strongly encouraged to initiate
                          antiretroviral regimens under the following
                          conditions: 1. Progression of disease (as
                          defined in the CPCRA Data Collection
                          Handbook). 2. A 50% drop in CD4 cell count
                          for patients whose average of the baseline
                          and randomization counts is 100 cells/mm3 or
                          greater. Due to the intra-person variability
                          of CD4 cell count measurements, this 50% drop
                          should be confirmed by a second CD4 cell
                          count. The following general clinical
                          guidelines may be applied for managing
                          toxicities (however, the general clinical
                          condition of the patient should always be
                          considered): 1. For Grade 1 toxicities, the
                          patient should be followed carefully, and the
                          antiretroviral drug(s) should be continued.
                          2. For Grade 2 toxicities, the patient should
                          be more carefully followed, with additional
                          laboratory and/or clinical appointments as
                          necessary, and the antiretroviral drugs may
                          be temporarily held at the clinician's
                          discretion. 3. For any Grade 3 toxicity that,
                          in the clinician's judgment, is due to the
                          antiretroviral drug(s), the causative
                          antiretroviral drug(s) and all other
                          antiretroviral agents should be withheld.
                          When possible, concomitant medications should
                          be held first at the discretion of the
                          investigator if he or she suspects that they
                          are contributing to the toxicity and not the
                          antiretroviral agents. Depending on the
                          nature and severity of the toxicity, the
                          degree to which it resolves, and/or the
                          emergence of alternative explanations for the
                          toxicity, or the patient's deterioration, the
                          antiretroviral drug(s) may be restarted at
                          the clinician's discretion. 4. For any Grade
                          4 toxicity, as well as any recurring Grade 3
                          toxicity, the antiretroviral drug(s) should
                          be temporarily held and may be permanently
                          stopped at the discretion of the clinician.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Community Consortium / UCSF 3180 18th St /
                          Suite 201 San Francisco, CA 94110 Carroll
                          Child [phone] Recruiting 000614.
COLORADO                  Denver CPCRA / Denver Public Hlth 605 Bannock
                          St Denver, CO 802044507 Jack Rouff
                          [phone] Recruiting 000614.
CONNECTICUT               Yale U / New Haven Med Ctr / AIDS Clinical
                          Trials Unit 135 College St / Suite 323 New
                          Haven, CT 065102483 Laurie Andrews
                          [phone] Recruiting 010228.
DISTRICT OF COLUMBIA      Washington Reg AIDS Prog / Dept of Infect Dis
                          VA Med Ctr / 50 Irving St NW Washington, DC
                          20422 Barbara Standridge [phone]
                          Recruiting 000614.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd #108 Chicago, IL 60657 Rita
                          Verheggen [phone] Recruiting 000614.
LOUISIANA                 Louisiana Comm AIDS Rsch Prog / Tulane Univ
                          Med 1430 Tulane Ave / TB 21 New Orleans, LA
                          70112 Janice Walker [phone] Recruiting
                          000614.
MICHIGAN                  Henry Ford Hosp 2799 West Grand Blvd /
                          CFP-104 Detroit, MI 48202 Diane Mastro-Polak
                          [phone] Recruiting 000614.
MICHIGAN                  Wayne State Univ - WSU/DMC / Univ Hlth Ctr
                          4201 Saint Antoine / POD 7C Detroit, MI 48201
                          Jan Kosmyna [phone] Recruiting 000614.
NEW JERSEY                Southern New Jersey AIDS Clinical Trials Dept
                          of Medicine / 3 Cooper Plaza / Suite 513
                          Camden, NJ 08103 Carol Graeber [phone]
                          Recruiting 000614.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Robert C Sawyer [phone]
                          Recruiting 000614.
NEW YORK                  Bronx-Lebanon Hosp Ctr Vaccine Trial Site /
                          1645 Grand Concourse Suite 1G Bronx, NY 10453
                          Elizabeth Doramajian [phone] Recruiting
                          010118.
NEW YORK                  Harlem AIDS Treatment Grp / Harlem Hosp Ctr
                          506 Lenox Ave / Rm 3101A New York, NY 10037
                          Luis Fuentes [phone] Recruiting 000614.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn St Portland, OR 97210 Norma Martinez
                          [phone] No longer recruiting 000111.
PENNSYLVANIA              Philadelphia FIGHT 1233 Locust St / 5th Floor
                          Philadelphia, PA 19107 Barbara Gallagher
                          [phone] Recruiting 000614.
TEXAS                     Montrose Clinic 215 Westheimer Rd Houston, TX
                          77006 Brian Bell [phone] Recruiting
                          010119.
TEXAS                     Houston Veterans Administration Med Ctr 2002
                          Holcombe Blvd Houston, TX 77030 Katharine
                          Breaux [phone] Recruiting 010115.
TEXAS                     Univ TX Health Science Ctr 6431 Fannin St
                          Houston, TX 77030 Hilda Cuervo [phone]
                          Recruiting 010115.
VIRGINIA                  Richmond AIDS Consortium / Div of Infect
                          Diseases PO Box 980049 Richmond, VA 232980049
                          Vinnie Mitchell [phone] Recruiting
                          000707.

77
UNIQUE IDENTIFIER         NIH/01278
PROTOCOL ID NUMBERS       NIAID HVTN 203
PROTOCOL TITLE            A Phase II Clinical Trial to Evaluate the
                          Immunogenicity and Safety of a Combined
                          Regimen Using ALVAC vCP1452 and AIDSVAX B/B.
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Preventative HIV Vaccine
GENERAL DESCRIPTION       PURPOSE: To confirm safety of ALVAC-HIV
                          vCP1452 in a study population similar to that
                          proposed for Phase III studies. To
                          characterize the safety of ALVAC vCP1452
                          given in combination with subunit rgp120
                          formulated in alum adjuvant [AS PER AMENDMENT
                          10/12/00: aluminum hydroxide adjuvant]. To
                          define the frequency of CD8+ CTL responses
                          induced by ALVAC vCP1452 alone [AS PER
                          AMENDMENT 10/12/00: (Group A)] or in
                          combination with B/B rgp120 (Groups A and B)
                          [AS PER AMENDMENT 10/12/00: (Groups B and
                          C)].
GENERAL DESCRIPTION       RATIONALE: There is no cure for HIV infection
                          or AIDS, and drug therapy is too expensive
                          for most affected populations. For this
                          reason, the development of safe, effective
                          vaccines to prevent HIV infections worldwide
                          is needed. ALVAC vCP1452 and MN rgp120/HIV-1
                          have been shown to be well tolerated in Phase
                          I and II studies. ALVAC vCP1452 given alone
                          or in combination with subunit antigens [AS
                          PER AMENDMENT 10/12/00: antigen] is a
                          candidate vaccine to be evaluated for the
                          ability to produce and express vaccine
                          antigen in greater quantity for a longer time
                          and with improved immunogenicity.
GENERAL DESCRIPTION       METHODOLOGY: Volunteers are randomized to 1
                          of 7 [AS PER AMENDMENT 10/12/00: 1 of 4]
                          groups and stratified by risk status. Prior
                          to immunization, evaluations and blood draws
                          are done to monitor hematological, chemical,
                          and immunologic parameters. Volunteers
                          receive 2 injections of the following
                          vaccines at Months 0, 1, 3, and 6: Group A:
                          ALVAC vCP1452 and alum placebo [AS PER
                          AMENDMENT 10/12/00: AIDSVAX placebo (aluminum
                          hydroxide adjuvant)] at Months 0, 1, 3, and
                          6. Group B: ALVAC vCP1452 and alum placebo
                          [AS PER AMENDMENT 10/12/00: AIDSVAX placebo]
                          at Months 0 and 1 and ALVAC vCP1452 and
                          AIDSVAX B/B at Months 3 and 6. Group C: ALVAC
                          placebo and alum placebo. [AS PER AMENDMENT
                          10/12/00: ALVAC vCP1452 and AIDSVAX B/B at
                          Months 0, 1, and 6 and ALVAC vCP1452 and
                          AIDSVAX placebo at Month 3.] Group D: ALVAC
                          vCP1452 and alum placebo at Months 0 and 1
                          and ALVAC vCP1452 and MN rgp120 at Months 3
                          and 6. [AS PER AMENDMENT 10/12/00: ALVAC
                          placebo and AIDSVAX placebo at Months 0, 1,
                          3, and 6.] Group E: ALVAC vCP1452 and AIDSVAX
                          B/B at Months 0, 1, and 6; ALVAC vCP1452 and
                          alum placebo at Month 3. [AS PER AMENDMENT
                          10/12/00: Group E has been discontinued.]
                          Group F: ALVAC vCP1452 and AIDSVAX B/B. [AS
                          PER AMENDMENT 10/12/00: Group F has been
                          discontinued.] Group G: ALVAC vCP1452 and
                          alum placebo at Months 0 and 1; ALVAC vCP1452
                          and AIDSVAX B/E at Months 3 and 6. [AS PER
                          AMENDMENT 10/12/00: Group G has been
                          discontinued.] Following each pair of
                          injections, volunteers are observed in the
                          clinic for 30 minutes. Volunteers keep a
                          record of body temperature and any other
                          symptoms and report results to their AIDS
                          Vaccine Evaluation Unit. Evaluations are
                          performed by telephone or clinic visit on
                          Days 1 and 2 after each vaccination. [AS PER
                          AMENDMENT 10/12/00: Volunteers record all
                          relevant signs and symptoms occurring 48
                          hours after each vaccination and provide that
                          information at each clinic visit.] HIV
                          testing is conducted every 3 to 6 months and
                          volunteers are asked to complete social harms
                          questionnaires once at Day 168 and once at
                          the end of the study. Volunteers are followed
                          on the study for a minimum of 18 months after
                          the first immunization. Safety is evaluated
                          by closely monitoring for local and systemic
                          adverse reactions during the course of the
                          trial.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Vaccine
                          prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 330 patients. [AS PER
                          AMENDMENT 10/12/00: 120 volunteers will be
                          randomized to Group A; 120 volunteers will be
                          randomized to Groups B and C (60 volunte
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 18 months, with
                          possible extension depending on the safety
                          and immunogenicity results..
PROTOCOL DETAILS          ACTUAL ACCRUAL: 326/330 010731.
PROTOCOL DETAILS          STUDY DURATION: 18 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 10
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (001012)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AVEG 203
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must
                          have: 1. HIV-negativity using ELISA within 8
                          weeks of immunization. 2. Normal history and
                          physical examination. 3. Availability for
                          follow-up for planned duration of the study
                          (12 months). 4. Absolute CD4 cell count of
                          400 cells/mm3 or more.
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 32% for women; >= 38% for men.
PATIENT INCLUSION CRIT.   PLATELET COUNT: 125000 to 550000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN Institutional ULN
                          (Upper Limit of Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: White count: 3,500 to 12,000
                          cells/mm3. Differential within institutional
                          normal limits or approval of site physician.
                          Total lymphocyte count: >= 800 cells/mm3.
                          Negative hepatitis B surface antigen. Normal
                          urine dipstick with esterase and nitrite.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 3 days prior
                          to study entry Not pregnant Abstinence or
                          effective method of birth control /
                          contraception 1 month before and during the
                          study.
PATIENT INCLUSION CRIT.   RISK BEHAVIOR: Forty percent or more, must
                          have 1 of the following: 1. Lower-risk sexual
                          behavior as defined by AVEG [AS PER AMENDMENT
                          10/12/00: HVTN] (i.e., meeting the criteria
                          for AVEG [AS PER AMENDMENT 10/12/00: HVTN]
                          Risk Group A or B). 2. Higher-risk sexual
                          behavior or
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 60 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Volunteers with
                          the following prior conditions are excluded:
                          1. History of immunodeficiency, chronic
                          illness, or autoimmune disease. 2. History of
                          cancer, unless there has been surgical
                          excision followed by a sufficient observation
                          period to give a reasonable assurance of
                          cure. 3. History of suicide attempts within 3
                          years or recent suicidal ideation. 4. History
                          of requirement for antipsychotic medication.
                          5. History of anaphylaxis or other serious
                          adverse reactions to vaccines. [AS PER
                          AMENDMENT 10/12/00: History of reaction to
                          thimerosal is no longer excluded.].
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Receipt of blood
                          products in the past 6 months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Immunosuppressive medications. 2. Live
                          attenuated vaccines within 60 days of study.
                          Medically indicated subunit or killed
                          vaccines (e.g., influenza, pneumococcal) are
                          not exclusionary but should be given at least
                          2 weeks away from HIV immunizations. 3. Use
                          of experimental agents within 30 days prior
                          to study. 4. Receipt of immunoglobulin in the
                          past 6 months. 5. HIV-1 vaccines or placebo
                          if received in a previous HIV vaccine trial.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Volunteers with the following
                          symptoms or conditions are excluded: 1.
                          Medical or psychiatric condition or
                          occupational responsibilities which preclude
                          volunteer compliance with the protocol. 2.
                          Present requirement for antipsychotic
                          medication. 3. Active syphilis. If the
                          serology is documented to be a false positive
                          or due to a remote (greater than 6 months)
                          treated infection, the volunteer is eligible.
                          4. Active tuberculosis (TB). Volunteers with
                          a positive PPD and a normal chest X-ray
                          showing no evidence of TB and not requiring
                          INH therapy are eligible. 5. Immediate-type
                          hypersensitive reaction to egg products or
                          neomycin.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0305  ALVAC(2)120(B,MN)GNP
                          (vCP1452)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0295  MN rgp120/HIV-1 and GNE8
                          rgp120/HIV-1
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Groups A, B, and C:
                          1.0 ml at Months 0, 1, 3, and 6. Drug 2:
                          Group B: 1.0 ml at Months 3 and 6. Group C:
                          1.0 ml at Months 0, 1, and 6
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular,
                          (10^7.26 TCID50)/ml. Drug 2: Intramuscular,
                          (300 mcg MN rgp120 and 300 mcg GNE8
                          rgp120)/ml
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 months, with possible
                          extension depending on the safety and
                          immunogenicity results.
OTHER TREATMENT INFO.     END POINT: Safety (occurrence of severe
                          systemic and severe local reactions) and
                          immunologic (humoral immune and cellular
                          immune responses to HIV-1).
OTHER TREATMENT INFO.     DISCONTINUE: Volunteers may be discontinued
                          for the following reasons: 1. HIV infection.
                          Volunteers identified as HIV-infected will be
                          offered enrollment in a follow-up protocol
                          and referred to private health care providers
                          for treatment (antiretroviral medications are
                          not provided by this study) and management of
                          the HIV-1 infection. 2. Pregnancy. 3. Grade
                          IV local adverse or systemic event classified
                          as probably or definitely associated with
                          immunization. 4. Type I hypersensitivity
                          associated with immunization. 5. Serious
                          intercurrent illness that is not expected to
                          resolve prior to the next scheduled
                          immunization. 6. Repeated compliance failure.
                          7. Request by volunteer.
SUPPORTING AGENCY         NIAID / Vaccine and Prevention Research
                          Program.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham Dept of
                          Medicine / 845 19th Street South Birmingham,
                          AL 35294 Peter Bonventre [phone] No
                          longer recruiting 010409.
MARYLAND                  Johns Hopkins Univ School of Hygiene and
                          Public Health 624 N Broadway / 125 Hampton
                          House Baltimore, MD 21205 Eric Zimmerman
                          [phone] No longer recruiting 010409.
MARYLAND                  Univ of Maryland Institute of Human Virology
                          725 W Lombard St Baltimore, MD 212011192
                          Lynda Nerhood [phone] Recruiting
                          010606.
MISSOURI                  Saint Louis Univ Health Sciences Ctr Division
                          of Infectious Diseases / 3635 Vista Ave /
                          FDT-8N Saint Louis, MO 63110 Carolyn Novotny
                          [phone] No longer recruiting 010409.
NEW YORK                  Univ of Rochester Med Ctr Box 689 / 601
                          Elmwood Ave Rochester, NY 14642 Shirley Erb
                          [phone] No longer recruiting 010409.
NEW YORK                  Columbia Univ 630 West 168th St New York, NY
                          10032 Jolene Noel-Connor [phone]
                          Recruiting 010529.
NEW YORK                  New York Blood Ctr Project ACHIEVE / 1309
                          Fulton Ave Room 312 Bronx, NY 10456 Pamela
                          Brown-Peterside [phone] Recruiting
                          010529.
RHODE ISLAND              Miriam Hosp 164 Summit Ave Providence, RI
                          02906 Gail Yates [phone] Recruiting
                          010503.
TENNESSEE                 Vanderbilt Univ Hosp A-3310 MCN / 21st and
                          Garland Nashville, TN 37232 Lois Wagner
                          [phone] No longer recruiting 010409.
WASHINGTON                Univ of Washington / Fred Hutchinson Cancer
                          Research Research Center AIDS Vaccine
                          Evaluation Unit / Cabrini Med ToweSeattle, WA
                          98104 David Berger [phone] No longer
                          recruiting 010409.

78
UNIQUE IDENTIFIER         NIH/01276
PROTOCOL ID NUMBERS       NIAID ACTG A5030
PROTOCOL TITLE            A Phase III, Prospective, Randomized,
                          Double-Blind Trial of Valganciclovir
                          Pre-Emptive Therapy for Cytomegalovirus (CMV)
                          Viremia as Detected by Plasma CMV DNA PCR
                          Assay.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To evaluate the effectiveness of
                          pre-emptive oral valganciclovir in preventing
                          cytomegalovirus (CMV) end-organ disease (EOD)
                          development and/or death in high-risk
                          patients identified by screening for plasma
                          CMV DNA positivity. To evaluate the safety of
                          pre-emptive valganciclovir for prevention of
                          CMV EOD development in high-risk patients
                          identified by screening for plasma CMV DNA
                          positivity.
GENERAL DESCRIPTION       RATIONALE: Patients receiving highly active
                          antiretroviral therapy (HAART), who, despite
                          HAART have an absolute CD4 count below
                          100/mm3, may be at risk of CMV EOD. This high
                          risk justifies testing a strategy of
                          screening patients for CMV viremia and
                          pre-emptively treating those who are viremic,
                          with potent anti-CMV therapy. Additionally,
                          patients who develop CMV retinitis or other
                          EOD will be followed for response to therapy.
GENERAL DESCRIPTION       METHODOLOGY: Step 1: Patients have an
                          ophthalmologic exam every 24 weeks and are
                          screened every 8 weeks for CMV viremia.
                          Patients positive for CMV DNA at entry to
                          Step 1 or who develop a qualitatively
                          positive result are randomized 1:1 to Step 2.
                          If CMV EOD develops prior to randomization to
                          Step 2, patients are encouraged to enter Step
                          3. Step 2: Patients receive either
                          valganciclovir or placebo. Patients are
                          monitored for development of CMV EOD with an
                          ophthalmologic exam and an extra-ocular CMV
                          symptoms questionnaire every 8 weeks. Blood
                          samples for CMV viremia continue to be
                          collected every 8 weeks. Patients who develop
                          CMV EOD progress to Step 3. Step 3: Patients
                          are followed every 12 weeks with an
                          ophthalmologic exam, other clinical and
                          laboratory evaluations, and a quality-of-life
                          assessment. Valganciclovir therapy is offered
                          to patients with CMV retinitis for 3 weeks or
                          more if retinitis remains active. Antiviral
                          resistance is assessed in all patients in
                          Step 3. All patients in all steps are
                          followed to a final closing date. After the
                          study is closed, valganciclovir is provided
                          for patients in Step 3 who are receiving
                          valganciclovir for treatment of CMV
                          retinitis, under the auspices of Roche, until
                          it is approved for marketing.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug prophylaxis, Treatment IND.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 750 patients. Step 1: 750
                          patients of whom at least 150 will be
                          randomized to Step 2.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Patients will
                          be on study from date of enrollment until
                          closing date of the study.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 151/750 010717.
PROTOCOL DETAILS          STUDY DURATION: 2.5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 49
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (000322)
PROTOCOL DETAILS          DISEASE STUDIED: Cytomegalovirus.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5030
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Placebo-Controlled Trial;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 antigen, HIV-1
                          RNA, HIV-1 culture, or a second antibody test
                          by method other than ELISA. 2. Written
                          consent of parent or guardian if under 18. 3.
                          CD4 cell count below 100 cells/mm3 performed
                          at an ACTG certified laboratory within 30
                          days prior to study entry. 4. Plasma HIV RNA
                          greater than 400 copies/ml using either the
                          Standard Roche Amplicor HIV-Monitor or the
                          Ultrasensitive Roche Amplicor HIV-Monitor
                          within 30 days prior to study entry. 5.
                          Presence of serum CMV IgG antibodies.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl Within 21 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 20000 cells/mm3 Within 21
                          days prior to study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 100 cells/mm3 Within
                          30 days prior to study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3 x ULN ULN (Upper Limit of
                          Normal). Within 21 days prior to study entry.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Within 21 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN Within 21 days prior to
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min Within 21
                          days prior to study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant Negative pregnancy test.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: HAART, defined as
                          at least a three-drug antiretroviral regimen
                          including at least one PI and/or
                          nonnucleoside reverse transcriptase
                          inhibitors (NNRTI), continuously for at least
                          3 months. Patients on a three-drug nucleoside
                          reverse transcriptase inhibitor (NRTI)
                          regimen may be enrolled if they have been
                          treated in the past for at least 30 days with
                          a PI or NNRTI. (Patients not receiving HAART
                          and not planning to initiate HAART for at
                          least 3 months after entering the study are
                          also eligible.).
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Permitted: Acyclovir,
                          famciclovir, and valacyclovir may be used for
                          the acute treatment and/or suppression of
                          herpes simplex or herpes zoster. Permitted
                          with caution: 1. Didanosine. 2. Zidovudine.
                          Permitted with caution during Step 2:
                          Myelosuppressive agents (the use of G-CSF is
                          permitted and should be recorded on the
                          appropriate case report forms when
                          administered).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Prior history of CMV EOD.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. HAART, defined
                          as at least a three-drug antiretroviral
                          regimen including at least one PI and/or
                          nonnucleoside reverse transcriptase
                          inhibitors, and not planning to initiate
                          HAART for at least 3 months after entering
                          the study. Patients on a three-drug
                          nucleoside reverse transcriptase inhibitor
                          (NRTI) regimen may be enrolled if they have
                          been treated in the past for at least 30 days
                          with a PI or NNRTI. (Patients who have been
                          receiving HAART continuously for at least 3
                          months are eligible.) 2. Oral or IV
                          ganciclovir, benzimidavir, lobucavir,
                          foscarnet, cidofovir, and CMV hyperimmune
                          globulin for CMV antiviral prophylaxis within
                          8 weeks prior to study entry. 3. Approved or
                          investigational agents with known anti-CMV
                          activity.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded during Steps
                          1 and 2: 1. Oral or IV ganciclovir,
                          benzimidavir, lobucavir, foscarnet,
                          cidofovir, and CMV hyperimmune globulin. 2.
                          Other approved or investigational agents with
                          known anti-CMV activity.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0271  Valganciclovir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Step 2: 900 mg bid
                          for 3 weeks, then 900 mg qd for 9 wethen 450
                          mg qd. Step 3: 900 mg bid for 3 weeks, then
                          900 mg qd for 3 weeks or
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Step 2: 12 weeks or more;
                          Step 3: 3 weeks or more.
OTHER TREATMENT INFO.     END POINT: Time from Step 2 randomization to
                          the diagnosis of CMV EOD; and safety and
                          tolerability of valganciclovir assessed by
                          the number of patients reporting
                          treatment-related toxicity or adverse events
                          of Grade 2 or higher.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued
                          from Steps 1, 2, and 3 for the following
                          reasons: 1. Request by patient. 2.
                          Noncompliance by patient and/or legal
                          guardian. 3. Investigator determines
                          continuing the study would be detrimental to
                          the patient. 4. Pregnancy. 5. Illness. 6.
                          Study withdrawal by AACTG, NIAID, FDA,
                          investigator, or pharmaceutical sponsor.
                          Patients may be discontinued from Step 1 for
                          the following reasons: 1. Patient becomes CMV
                          DNA PCR positive and refuses Step 2
                          randomization. 2. Patient experiences CMV EOD
                          and refuses Step 3 registration. 3. Patient
                          requires medication with anti-CMV activity.
                          4. Patient does not meet laboratory criteria
                          for Step 2 within 12 weeks of CMV DNA
                          positivity. Patients may be discontinued from
                          Step 2 for the following reasons: 1. Refusal
                          to participate in Step 3. 2. Requirement for
                          medication with anti-CMV activity. All
                          patients meeting discontinuation criteria
                          should have evaluations as described in the
                          protocol.
OTHER TREATMENT INFO.     MODIFICATION: Doses are reduced for Grade 4
                          neutropenia, for Grade 4 thrombocytopenia,
                          for Grade 4 anemia, renal impairment, and
                          other adverse events (i.e., new toxicities of
                          Grade 3 or higher other than neutropenia,
                          thrombocytopenia, anemia, or total bilirubin
                          up to 2.5 x ULN and Grade 3 or higher
                          toxicity recurring more than 30 days after
                          the study drug is held). If any toxicity
                          persists for more than 30 days after dose
                          reduction or recurs more than 3 times,
                          discontinue all study medications unless
                          discussed with the protocol chairs/vice
                          chairs.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 000817.
CALIFORNIA                Marin County Specialty Clinic 161 Mitchell
                          Building Suite 200 San Rafael, CA 94903 Marc
                          Gould [phone] Recruiting 000817.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 000817.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 000922.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 000810.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          000817.
CALIFORNIA                Santa Clara Valley Med Ctr / AIDS Community
                          Rsch Consortium 751 South Bascom Ave San
                          Jose, CA 951282699 Debbie Slamowitz
                          [phone] Recruiting 000817.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 000817.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 000914.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 000817.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000817.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 000829.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Beth Dean [phone] Recruiting
                          000817.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          000817.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] No longer recruiting
                          010320.
ILLINOIS                  Cook County Hosp 1835 W Harrison St Chicago,
                          IL 60612 Joanne Despotes [phone]
                          Recruiting 001012.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 000817.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 000817.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 000817.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 000817.
MASSACHUSETTS             Harvard (Massachusetts Gen Hosp) 55 Fruit St
                          / Founders Bldg 8th Floor Boston, MA 02114
                          Teri Flynn [phone] Recruiting 000914.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 000817.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Rebecca Becker
                          [phone] Recruiting 010723.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 000817.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Barbara
                          Longmire [phone] Recruiting 000817.
NEW YORK                  St Mary's Hosp (Univ of Rochester/Infectious
                          Diseases) 601 Elmwood Ave Rochester, NY 14642
                          Carol Greisberger [phone] Recruiting
                          000817.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 000817.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 000817.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 001012.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Ross Hewitt
                          [phone] Recruiting 000823.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] Recruiting 000815.
NEW YORK                  Cornell Clinical Trials Unit 119 West 24th St
                          / Ground Floor New York, NY 10011 Todd
                          Stroberg [phone] Recruiting 000817.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 000817.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 000817.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Valery Hughes [phone]
                          Recruiting 000817.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 000829.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 000817.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 001006.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 001013.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 001121.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          000817.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000823.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 000823.
RHODE ISLAND              Brown Univ / The Miriam Hosp 164 Summit Ave /
                          Research Building / Room 215 Providence, RI
                          02906 Joan Gormley [phone] Recruiting
                          010108.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 000823.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 000914.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone]
                          Recruiting 000817.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 000817.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 000817.

79
UNIQUE IDENTIFIER         FDA/01271
PROTOCOL ID NUMBERS       FDA B009
PROTOCOL TITLE            A Randomized, Double-Blind,
                          Adjuvant-Controlled, Multicenter Study to
                          Compare the Virologic and Immunologic Effect
                          of Highly Active Antiretroviral Therapy
                          (HAART) Plus Remune Versus HAART Plus
                          Incomplete Freund's Adjuvant (IFA) in
                          Antiretroviral-Naive Patients Infected with
                          Human Immunodeficiency Virus Type 1 (HIV-1).
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Vaccine
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To determine whether the addition of
                          Remune to a HAART regimen of Viracept
                          (nelfinavir mesylate) and Combivir
                          (zidovudine and lamivudine) delays the time
                          to virologic failure. Methodology: All
                          patients begin HAART at study entry (Day 1).
                          Patients with a plasma HIV-1 RNA level less
                          than or equal to 2,000 copies/ml at Week 8
                          are randomized to receive Remune or
                          Incomplete Freund's Adjuvant (IFA) at Week 9.
                          Patients who do not achieve a plasma HIV-1
                          RNA level of less than or equal to 2,000
                          copies/ml at Week 8 are not randomized and
                          are terminated from the study. These patients
                          are eligible to receive funding for up to a
                          3-month supply of nelfinavir (Viracept) and
                          Combivir. Randomized patients receive Remune
                          or IFA at Week 9 and approximately every 12
                          weeks thereafter until study completion (when
                          the last patient reaches Week 48). Patients
                          are considered virologic failures if they (1)
                          fail to achieve a virologic response by Week
                          48 or (2) after achieving a virologic
                          response, have a virologic relapse.
                          Regardless of their previous response status,
                          patients whose plasma HIV-1 RNA level
                          increases to greater than 2,000 copies/ml
                          while they are receiving protocol-specified
                          HAART are eligible to receive salvage therapy
                          and continue to receive Remune or IFA until
                          study completion. Study visits occur at
                          screening, Day 1, Weeks 4, 8, 9, 12, and then
                          every 4 weeks thereafter until the last
                          patient reaches Week 48. Patients who
                          complete this study are eligible to
                          participate in a rollover study.
GENERAL DESCRIPTION       METHODOLOGY: All patients begin HAART at
                          study entry (Day 1). Patients with a plasma
                          HIV-1 RNA level less than or equal to 2,000
                          copies/ml at Week 8 are randomized to receive
                          Remune or Incomplete Freund's Adjuvant (IFA)
                          at Week 9. Patients who do not achieve a
                          plasma HIV-1 RNA level of less than or equal
                          to 2,000 copies/ml at Week 8 are not
                          randomized and are terminated from the study.
                          These patients are eligible to receive
                          funding for up to a 3-month supply of
                          nelfinavir (Viracept) and Combivir.
                          Randomized patients receive Remune or IFA at
                          Week 9 and approximately every 12 weeks
                          thereafter until study completion (when the
                          last patient reaches Week 48). Patients are
                          considered virologic failures if they (1)
                          fail to achieve a virologic response by Week
                          48 or (2) after achieving a virologic
                          response, have a virologic relapse.
                          Regardless of their previous response status,
                          patients whose plasma HIV-1 RNA level
                          increases to greater than 2,000 copies/ml
                          while they are receiving protocol-specified
                          HAART are eligible to receive salvage therapy
                          and continue to receive Remune or IFA until
                          study completion. Study visits occur at
                          screening, Day 1, Weeks 4, 8, 9, 12, and then
                          every 4 weeks thereafter until the last
                          patient reaches Week 48. Patients who
                          complete this study are eligible to
                          participate in a rollover study.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010711)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 688 patients. Enrollment
                          in this study will continue until 550
                          patients have been randomized to Remune or
                          IFA. With the expectation that up to 20% of t
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: All patients
                          are followed until the last patient reaches
                          Week 48.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/688.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AG1661-202
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Multicenter Study; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 seropositivity as confirmed by
                          ELISA and Western blot. 2. Plasma HIV-1 RNA
                          level greater than or equal to 10,000
                          copies/ml at screening. 3. CD4 lymphocyte
                          count greater than or equal to 250 cells/mm3
                          at screening.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 250 cells/mm3.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Prior
                          antiretroviral therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0247  HIV-1 Immunogen
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0285  Lamivudine/Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0263  Nelfinavir mesylate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 1 ml (10 microg/ml
                          p24) approximately every 12 weeks starting at
                          Week 9. Drug 2: Zidovudine 300 mg/lamivudine
                          150 mg bid. Drug 3: 1250 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 2: Zidovudine 600
                          mg/lamivudine 300 mg. Drug 3: 2500 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Injection into deltoid
                          muscle. Drug 2: Oral. Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Patients receive an
                          injection of Remune or IFA at Week 9 and
                          approximately every 12 weeks thereafter until
                          the last patient reaches Week 48.
OTHER TREATMENT INFO.     END POINT: The primary efficacy endpoint is
                          time to virologic failure. Evaluation of
                          safety is based on a comparison between
                          treatment groups of the following parameters:
                          incidence, severity, and relationship to
                          study medications of individual adverse
                          events and incidence of marked changes in
                          laboratory values.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: Failure to achieve
                          a plasma HIV-1 RNA level less than or equal
                          to 2,000 copies/ml at Week 8.
SUPPORTING AGENCY         Agouron Pharmaceuticals Inc.
LAST REVISION DATE        20010711
CALIFORNIA                Agouron Pharmaceuticals Inc 11095 Torreyana
                          Rd San Diego, CA 92121 Merril Gertsen
                          [phone] Recruiting.

80
UNIQUE IDENTIFIER         FDA/01267
PROTOCOL ID NUMBERS       FDA 259H
PROTOCOL TITLE            A Randomized, Open-label, Study of Nelfinavir
                          or Efavirenz in HIV-1 Infected,
                          Antiretroviral Naive Patients.
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To compare the response to an
                          initial and subsequent antiretroviral (ARV)
                          regimen in patients starting therapy with
                          nelfinavir (NFV) versus efavirenz (EFV). To
                          compare the immunologic response (both
                          reconstitution and activation) to initial
                          regimens containing NFV versus EFV. An
                          immunologic and virologic substudy and a
                          metabolic substudy will assess respective
                          markers (lymphoid tissue, viral phenotype,
                          genotype, and fitness and other markers of
                          immune function and changes in glucose
                          regulation, lipid metabolism, and body fat
                          distribution). Methodology: Patients are
                          randomized to initiate therapy and receive
                          either nelfinavir (NFV) or efavirenz (EFV) in
                          the first regimen (R1). All patients also
                          receive zidovudine (AZT) and lamivudine
                          (3TC). Patients are further randomized in a
                          factorial fashion and by stratification based
                          on HIV RNA level (less than 10,000,
                          10,000-100,000, or greater than 100,000
                          copies/ml) to be administered a single
                          injection of a neo-antigen (KLH) at Week 12,
                          24, or 48. Therapy continues until switch
                          criteria are met either before or after Week
                          24. When switch criteria are met, patients
                          advance to the next regimen (R2). R2 patients
                          previously taking NFV switch to EFV; those
                          randomized to EFV switch to NFV; the
                          additional NRTIs change to stavudine (d4T)
                          and didanosine (ddI). Therapy is continued
                          for an additional 24 weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          initiate therapy and receive either
                          nelfinavir (NFV) or efavirenz (EFV) in the
                          first regimen (R1). All patients also receive
                          zidovudine (AZT) and lamivudine (3TC).
                          Patients are further randomized in a
                          factorial fashion and by stratification based
                          on HIV RNA level (less than 10,000,
                          10,000-100,000, or greater than 100,000
                          copies/ml) to be administered a single
                          injection of a neo-antigen (KLH) at Week 12,
                          24, or 48. Therapy continues until switch
                          criteria are met either before or after Week
                          24. When switch criteria are met, patients
                          advance to the next regimen (R2). R2 patients
                          previously taking NFV switch to EFV; those
                          randomized to EFV switch to NFV; the
                          additional NRTIs change to stavudine (d4T)
                          and didanosine (ddI). Therapy is continued
                          for an additional 24 weeks.
PROTOCOL PHASE            Phase IV
OPEN/CLOSED INDICATOR     Open (010711)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Treatment IND.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 200 patients. 100 for each
                          of 2 treatment arms.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 72 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/200.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (990923)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AG1343-1127
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Cross-Over Study; Factorial Design Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Plasma HIV-1 RNA
                          of at least 5000 copies/ml. 3. CD4 count of
                          at least 100 cells/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Antiretroviral
                          therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0070  Keyhole-Limpet Hemocyanin
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0269  Efavirenz
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 1250 mg bid. Drug 6:
                          Single injection. Drug 7: 600 mg qd
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 2500 mg. Drug 7: 600mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral. Drug 5: Oral.
                          Drug 6: Injection. Drug 7: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 72 weeks.
OTHER TREATMENT INFO.     END POINT: Time to failure of the second
                          treatment regimen (with failure defined as
                          HIV RNA level greater than 50 copies/ml);
                          immunologic response to initial regimens
                          (primary markers for this analysis are CD4,
                          CD4CD45RO, CD4CD45RACD62L, CD4 and CD8 TREC
                          level, and CD8CD38DR); and toxicity.
SUPPORTING AGENCY         Agouron Pharmaceuticals Inc.
LAST REVISION DATE        20010711
CALIFORNIA                Agouron Pharmaceuticals Inc 11095 Torreyana
                          Rd San Diego, CA 92121 Carolyn Peterson
                          [phone] Recruiting.

81
UNIQUE IDENTIFIER         NIH/01261
PROTOCOL ID NUMBERS       NIAID ACTG A5067
PROTOCOL TITLE            Study of Pathogen-Specific Immune Responses
                          and General Immune Competence in
                          Opportunistic Infections.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare pathogen-specific immune
                          activity by lymphocyte proliferation assay
                          (LPA) in patients presenting with
                          Pneumocystis carinii pneumonia (PCP),
                          cytomegalovirus (CMV) retinitis, or [AS PER
                          AMENDMENT 4/17/01: The following text has
                          been deleted: histoplasmosis patients who are
                          not currently receiving potent antiretroviral
                          therapy; and has been replaced with the
                          following text: patients with CMV non-ocular
                          end organ disease,] and in patients who have
                          had secondary prophylaxis or maintenance
                          therapy withdrawn and do not develop clinical
                          recurrence of these opportunistic infections
                          (OIs) while on potent antiretroviral therapy;
                          to identify correlates of pathogen-specific
                          immunity. To compare LPA response between
                          patients who develop PCP to those who have
                          had PCP maintenance therapy withdrawn. To
                          compare LPA response between patients who
                          develop CMV [AS PER AMENDMENT 4/17/01:
                          retinitis or CMV non-ocular end organ
                          disease] to those who have had CMV
                          maintenance therapy withdrawn. [AS PER
                          AMENDMENT 4/17/01: The following sentence has
                          been deleted: To compare LPA response between
                          patients who develop histoplasmosis to those
                          who have had histoplasmosis maintenance
                          therapy withdrawn.]
GENERAL DESCRIPTION       RATIONALE: To better understand the
                          relationship between immunologic responses,
                          immune reconstitution, and the occurrence of
                          OIs, observational data need to be collected
                          (1) in patients who present with an OI before
                          initiation of potent antiretroviral therapy,
                          (2) in patients with a history of such OIs
                          who have had secondary prophylaxis or
                          maintenance therapy withdrawn and do not
                          develop OI recurrence after potent
                          antiretroviral therapy, and (3) in controls
                          who were exposed to the pathogen of interest
                          but never were at risk for disease because
                          their immunity was not severely compromised.
                          Immunologic comparisons may identify
                          correlates of protection for a group of
                          patients who do not develop an OI after
                          potent antiretroviral therapy-induced immune
                          reconstitution. Conversely, a subpopulation
                          of patients may be identified that lacks
                          critical host factors of protection and is
                          more likely to develop an OI after immune
                          reconstitution, and therefore would benefit
                          from continued prophylaxis, regardless of CD4
                          cell count.
GENERAL DESCRIPTION       METHODOLOGY: This study consists of 3 groups
                          and 8 [AS PER AMENDMENT 4/17/01: 6]
                          subgroups. Clinical microbiological data are
                          collected and samples are obtained for
                          immunologic assays (pathogen-specific and
                          general) in all groups at entry (time of OI
                          presentation for Group 1 patients) and at 12
                          weeks (except Group 3b). Group 1b patients
                          also are evaluated at 24 weeks [AS PER
                          AMENDMENT 4/17/01: The following text has
                          been deleted: and at the time of diagnosis of
                          immune-recovery vitreitis, if it should
                          develop]. [AS PER AMENDMENT 4/17/01: Once
                          patients in Groups 1, 2, and 3a have
                          completed the Week 12 evaluations, they will
                          be off-study.] Blood samples, 1 to 7 days
                          apart, for peripheral blood mononuclear cells
                          (PBMCs), LPA, and inducible cytokine
                          expression of interferon gamma,
                          interleukin-2, interleukin-4, and
                          interleukin-10 are obtained.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients. Group 1: 45
                          [AS PER AMENDMENT 4/17/01: 30] patients (15
                          each in Groups 1a, 1b, and 1c); Group 2: 45
                          [AS PER AMENDMENT 4/17/01: 30] patient
PROTOCOL DETAILS          ACTUAL ACCRUAL: 76/90 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 16
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010417)
PROTOCOL DETAILS          DISEASE STUDIED: Cytomegalovirus Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5067
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Longitudinal
                          Study; Nonrandomized Concurrent Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: All patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, positive PCR for
                          HIV proviral DNA, or a second antibody test
                          other than ELISA at any time prior to study
                          entry (except Group 3b). 2. Consent of parent
                          or guardian if under 18 years of age.
                          Patients in Group 1a must have: 1. Acute PCP.
                          [2. AS PER AMENDMENT 4/17/01: Entered the
                          study within 14 days of diagnosis of the OI.
                          3. Met 1 of the following conditions: (1)
                          Have received potent antiretroviral therapy
                          (regimen containing a protease inhibitor [PI]
                          or a nonnucleoside reverse transcriptase
                          Inhibitor [NNRTI]) or (2) have not received
                          potent antiretroviral therapy for at least 8
                          weeks prior to PCP presentation. 4. A CD4
                          cell count below 200 cells/mm3 within 14 days
                          of OI presentation.] Patients in Group 1b
                          must have: 1. CMV retinitis [AS PER AMENDMENT
                          4/17/01: or CMV non-ocular end organ
                          disease]. [2. AS PER AMENDMENT 4/17/01:
                          Entered the study within 14 days of diagnosis
                          of the OI. 3. Met 1 of the following
                          requirements: (1) have never received potent
                          antiretroviral therapy regimen containing a
                          PI or an NNRTI, (2) have not received potent
                          antiretroviral therapy for at least 8 weeks
                          prior to CMV presentation, or (3) have been
                          on stable antiretroviral therapy for at least
                          3 months with no new antiretroviral therapy
                          medications initiated between the time of CMV
                          presentation and second baseline blood draw.
                          4. A CD4 cell count below 50 cells/mm3 within
                          14 days of OI presentation if the patient
                          received antiretroviral therapy at any time
                          in the past. Note: Patients presenting with
                          CMV retinitis must be evaluated by an
                          experienced ophthalmologist using indirect
                          ophthalmoscopy.] Patients in Group 2a must
                          have: 1. A history of confirmed PCP and be
                          receiving potent antiretroviral therapy. 2.
                          Co-enrolled in ACTG 888. [3. AS PER AMENDMENT
                          4/17/01: Been off secondary PCP prophylaxis
                          for at least 48 weeks prior to study entry.
                          4. Not developed PCP while on potent
                          antiretroviral therapy.] 5. A CD4 cell count
                          above 200 cells/mm3 [AS PER AMENDMENT
                          4/17/01: within 28 days before study entry].
                          [Patients in Group 2b must have: AS PER
                          AMENDMENT 4/17/01: 1. A history of CMV
                          retinitis and are currently receiving potent
                          antiretroviral therapy. 2. Been off secondary
                          CMV prophylaxis for at least 12 weeks prior
                          to study entry. 3. Not developed CMV
                          retinitis while on potent antiretroviral
                          therapy. 4. A CD4 cell count above 50
                          cells/mm3 within 28 days before study entry.
                          5. An ophthalmologic exam confirming lack of
                          CMV retinitis activity within 28 days before
                          study entry.] Patients in Group 3a must have:
                          [1. AS PER AMENDMENT 4/17/01: A histoplasmin
                          skin test criterion has been deleted.] 2. CMV
                          seropositive status. 3. No history of PCP [AS
                          PER AMENDMENT 4/17/01: CMV retinitis, or CMV
                          non-ocular end organ disease]. 4. Had all CD4
                          counts of at least 200 cells/mm3. 5. Never
                          received prophylaxis for PCP, CMV retinitis,
                          or CMV non-ocular end organ disease. Patients
                          in Group 3b must have: 1. Absence of HIV-
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: [AS PER AMENDMENT
                          4/17/01: Group 1a: Below 200 cells/mm3 within
                          14 days of OI presentation. Group 1b: Below
                          50 cells/mm3 within 14 days of OI
                          presentation, if patient received
                          antiretroviral therapy at any time in the
                          past. Group
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: 1. Prednisone in
                          patients with PCP. 2. G-CSF.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Groups 2 and
                          3a patients must be on potent antiretroviral
                          therapy at the time of study entry. Allowed:
                          1. Adjuvant corticosteroid therapy in
                          patients with documented PCP and evidence of
                          severe disease (PO2 less than 70 mm Hg or A-a
                          gradient greater than 35). 2. G-CSF.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded from
                          Group 3b: HIV infection. [AS PER AMENDMENT
                          4/17/01: HIV-1 negative status must be
                          documented by a licensed ELISA test within 28
                          days before study entry.].
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current drug use
                          that could prevent compliance with scheduled
                          study visits, at the discretion of the local
                          investigator.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any
                          vaccination within 14 days prior to study
                          entry. 2. Any immunomodulator or
                          investigational therapy within 30 days prior
                          to study entry, except prednisone in patients
                          with PCP. 3. GM-CSF within 30 days prior to
                          study entry. (G-CSF is permitted.) Excluded
                          for patients in Group 1: 1. More than 14 days
                          of treatment for current OI. 2. Potent
                          antiretroviral therapy within 8 weeks before
                          study entry. Excluded for patients in Group
                          2: Secondary prophylaxis for OI within 48
                          weeks prior to enrollment (Group 2a), 12
                          weeks prior to enrollment (Group 2b), or 24
                          weeks prior to enrollment (Group 2c).
                          Excluded for patients in Group 3a:
                          Prophylaxis for PCP, CMV retinitis, or
                          histoplasmosis.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Vaccines.
                          2. Any immunomodulator or investigational
                          therapy except prednisone in patients with
                          PCP. 3. GM-CSF (G-CSF is allowed).
OTHER TREATMENT INFO.     END POINT: LPA response at entry.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Patient requests
                          withdrawal from this study at any time. 2.
                          Patient or legal guardian refuses to adhere
                          to study requirements as determined by the
                          investigator. 3. Investigator determines that
                          further participation would be detrimental to
                          the patient's health or well-being. 4.
                          Patient fails to comply with the study
                          requirements so as to cause harm to self or
                          seriously interfere with the validity of the
                          study results. Note: Patients who prematurely
                          discontinue must have the evaluations
                          outlined in the protocol completed within 4
                          weeks of discontinuation.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Marin County Specialty Clinic 161 Mitchell
                          Building Suite 200 San Rafael, CA 94903 Marc
                          Gould [phone] Recruiting 000424.
CALIFORNIA                Univ of California / San Diego Treatment Ctr
                          2760 5th Ave / Suite 300 San Diego, CA
                          921036325 Jill Kunkel [phone]
                          Recruiting 000531.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 001012.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          000424.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000424.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 000726.
ILLINOIS                  Children's Mem Hosp Family Cln / Northwestern
                          Univ Med Schl 303 East Superior St /
                          Passavant Pavilion / Room 823 Chicago, IL
                          60611 Baiba L Berzins [phone]
                          Recruiting 000726.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 000614.
INDIANA                   Wishard Hosp 550 N Univ Blvd / Room 5550
                          Indianapolis, IN 46202 Scott Hamilton
                          [phone] Recruiting 000614.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Rebecca Becker
                          [phone] Recruiting 010723.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone] No
                          longer recruiting 010501.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 000424.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 000621.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000515.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 001006.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 000817.

82
UNIQUE IDENTIFIER         FDA/01256
PROTOCOL ID NUMBERS       FDA 302B
PROTOCOL TITLE            Safety and Antiviral Efficacy of a Novel
                          HIV-1 Protease Inhibitor, BMS-232632, in
                          Combination Regimen(s) as Compared to a
                          Reference Combination Regimen(s) in
                          Antiretroviral-Experienced HIV-Infected
                          Subjects.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To compare the antiviral activity of
                          two dose levels of BMS-232632/saquinavir
                          (SQV) to ritonavir (RTV)/SQV in combination
                          with two reverse transcriptase inhibitors in
                          antiretroviral-experienced HIV-infected
                          patients. Methodology: This is a three-arm
                          study; patients are randomized to receive
                          BMS-232632 at two different doses or RTV in
                          combination with SQV and two nucleoside
                          analogues over 48 weeks. Randomization is
                          stratified for baseline phenotypic
                          sensitivity.
GENERAL DESCRIPTION       METHODOLOGY: This is a three-arm study;
                          patients are randomized to receive BMS-232632
                          at two different doses or RTV in combination
                          with SQV and two nucleoside analogues over 48
                          weeks. Randomization is stratified for
                          baseline phenotypic sensitivity.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (000815)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 38
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AI424-009
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Random
                          Allocation; Dose-Response Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. HIV RNA viral load
                          of at least 2,000 copies/ml. 3. CD4 cell
                          count of at least 100 cells/mm3 (or at least
                          75 cells/mm3 in patients with no prior
                          AIDS-defining illness). 4. Phenotypically
                          documented sensitivity to stavudine (d4T) or
                          zidovudine (ZDV) and didanosine (ddI) or
                          lamivudine (3TC) defined as less than 2.5
                          times the EC50 of the control strain. 5.
                          Phenotypically documented sensitivity to
                          BMS-232632, RTV, and SQV defined as less than
                          10 times the EC50 of the control strain. 6.
                          Availability for follow-up for a period of at
                          least 48 weeks.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3 or >=
                          75 cells/mm3 in patients with no prior
                          AIDS-defining illness.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN ULN (Upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Total serum lipase < 1.4 x ULN.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Patients must be
                          currently receiving an antiviral regimen
                          containing a protease inhibitor or a
                          nonnucleoside reverse transcriptase
                          inhibitor, and have been receiving this
                          regimen for at least 24 weeks. Patients must
                          have had documented virologic response to the
                          regimen (either a greater than 1.0 log
                          decline or a decline in viral load to below
                          400 copies/ml for Roche Amplicor or to below
                          500 copies/ml for Chiron bDNA).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic pancreatitis. 2.
                          Acute hepatitis within 30 days of study
                          entry. 3. History of bilateral peripheral
                          neuropathy. 4. Intractable diarrhea within 30
                          days of study entry.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          substance abuse.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Newly
                          diagnosed HIV-related opportunistic infection
                          or condition requiring acute therapy at the
                          time of enrollment. 2. Suspected primary
                          (acute) HIV infection. 3. Hemophilia. 4.
                          Inability to tolerate oral medications.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0164  Saquinavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0314  BMS-232632
SUPPORTING AGENCY         Bristol - Myers Squibb Pharmaceutical
                          Research Institute.
LAST REVISION DATE        20000815
ALABAMA                   Sorra Research Ctr / Med Forum 950 N 22nd St
                          / Suite 550 Birmingham, AL 35203 Bonnie
                          Brewer [phone] Recruiting 000208.
CALIFORNIA                Avalar Medical Group 5620 Wilbur Ave / Suite
                          320 Tarzana, CA 91356 Toni Sparrow
                          [phone] Recruiting 000208.
CALIFORNIA                Robert Scott MD 368 28th St at Summit
                          Oakland, CA 94609 Henry Quinones
                          [phone] Recruiting 000208.
CALIFORNIA                Univ of California - Davis Med Ctr / CARES
                          4150 V St / Suite 500 Sacramento, CA 95817
                          Shahrokh Jalali [phone] Recruiting
                          000208.
CALIFORNIA                AIDS Healthcare Foundation 1300 North Vermont
                          Ave Los Angeles, CA 90027 Edwin Graham
                          [phone] Recruiting 000208.
CONNECTICUT               Yale Univ School of Medicine / AIDS Program
                          135 College St / Suite 323 New Haven, CT
                          06510 Cynthia Frank [phone] Recruiting
                          000208.
FLORIDA                   Community Research Initiative of South
                          Florida 1320 South Dixie Hwy Coral Gables, FL
                          33146 Jean Telusma [phone] Recruiting
                          000208.
FLORIDA                   Infectious Disease Research Institute 4728
                          North Habana Ave Tampa, FL 33614 Kalliope
                          Halkias [phone] Recruiting 000208.
FLORIDA                   HIV Clinical Research 300 SE 17th St Fort
                          Lauderdale, FL 33316 Jason Villano
                          [phone] Recruiting 000208.
GEORGIA                   Infectious Disease Specialists of Atlanta
                          2665 N Decatur Rd / Suite 330 Decatur, GA
                          30033 Katie McClure [phone] Recruiting
                          000208.
LOUISIANA                 Louisiana State Univ Med Ctr / HIV Outpatient
                          Clinic 136 South Roman St New Orleans, LA
                          70112 Alison Fleury [phone] Recruiting
                          000208.
NEW YORK                  St Vincents Hosp / Clinical Research Program
                          36 7th Ave / Suite 415 New York, NY 10011
                          Daisy Soto-Coppola [phone] Recruiting
                          000208.
NEW YORK                  Albany Med College 47 New Scotland Ave / MC
                          142 Albany, NY 12208 Sandra Preston
                          [phone] Recruiting 000208.
OHIO                      Univ Hosps of Cleveland 2061 Cornell Rd /
                          Foley Bldg Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 000208.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn St Portland, OR 97210 Norma Martinez
                          [phone] Recruiting 000208.
OTHER                     Brennerstr 71 Hamburg, L Weitner Recruiting
                          000208.
OTHER                     Georg-Str 46 Hanover, Birger Kulmann
                          Recruiting 000208.
OTHER                     Hopital De L'Archet 1 Route St Antoine De
                          Ginestiere / BP 3079 Cedex 03 Nice, Pierre
                          Dellamonica Recruiting 000208.
OTHER                     Reparto Malattie Infettive Ospedale SM
                          Annunziata / Via Dell'Antella 58 Antella,
                          Francesco Mazzotta Recruiting 000208.
OTHER                     Ospedale Luigi Cacco Moroni Istituto di
                          Malattie Infettive / Via G B Grassi 74
                          Milano, M L Cargnel Recruiting 000208.
OTHER                     Hopital De L'Hotel Dieu Service Des Medecine
                          Interne B / Place Alexis Ricardeau Nantes,
                          Francois Raffi Recruiting 000208.
OTHER                     Clinical Malattie Infettive Ospedale San
                          Raffaele / Via Stamina D'Ancora 20 Milano,
                          Andriano Lazzarin Recruiting 000208.
OTHER                     Hopital De Haut Leveque Medecine Interne /
                          Avenue De Magellan Pessac, Prof Pellegrin
                          Recruiting 000208.
OTHER                     Ospedale degli Infermi Divisione Malattie
                          Infettive / Via Settembini 2 Rimini, R
                          Ciammarughi (37 )054- 1705 315 Recruiting
                          000208.
OTHER                     Hopital Pellegrin Tripode Place Amelie Raba
                          Leon Bordeaux, Jean Yves Lacut Recruiting
                          000208.
OTHER                     Clinical Malattie Infettive / Univ Modena Via
                          del Pozzo Modena, Bruno De Rienzo Recruiting
                          000208.
OTHER                     Hospital Gustave Dron 135 Rue du President
                          Coty Tourcoing, Yves Mouton (33 )3 2-0 69
                          4600 Recruiting 000208.
OTHER                     Praxisgemeinschaft Karlsplatz Munich, Hans
                          Jaeger Recruiting 000208.
OTHER                     Hopital Paul Brousse Service De Medecine
                          Interne / Pavillon Galilee Villejuif, Daniel
                          Vittecoq MD (145)593-000 Recruiting 000208.
OTHER                     Srev Du Pr Gentilini 47 Boulevard de Hospital
                          Paris Cedex 13, Christine Katlama Recruiting
                          000208.
OTHER                     Toronto Hosp 200 Elizabeth St Toronto, ON
                          Sharon Walmsley Recruiting 000208.
OTHER                     Ottawa General Hospital 501 Smyth Rd / Room
                          G12 Ottawa, ON Nanci Hawley-Foss
                          [phone] Recruiting 000208.
OTHER                     Montreal Chest Institute 3650 Rue St-Urbain
                          Montreal , QC John Macleod Recruiting 000208.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 000208.
TENNESSEE                 Vanderbilt Univ Med Ctr 1211 Twenty-first Ave
                          South Nashville, TN 37212 Victoria Harris
                          [phone] Recruiting 000208.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75235 Robert
                          Barber [phone] Recruiting 000208.
TEXAS                     Houston Clinical Research Network / Div of
                          Montrose Clinic 215 Westheimer Houston, TX
                          77006 Barbara Burkhardt [phone]
                          Recruiting 000208.
TEXAS                     Texas Tech Health Sciences Ctr 4800 Alberta
                          Ave El Paso, TX 79905 Arturo Norte
                          [phone] Recruiting 000208.

83
UNIQUE IDENTIFIER         NIH/01254
PROTOCOL ID NUMBERS       NIAID ACTG 402
PROTOCOL TITLE            Phase I/II Trial of Subcutaneous IL-2 with
                          Highly Active Antiretroviral Therapy in
                          HIV-Infected Children with Immunosuppression.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine the safety and highest
                          tolerated dose of subcutaneous interleukin-2
                          (IL-2) in HIV-infected children receiving
                          highly active antiretroviral therapy (HAART).
                          To compare the safety, tolerance, and
                          compliance of subcutaneous intermittent
                          high-dose IL-2 to subcutaneous low-dose IL-2.
                          To evaluate high- and low-dose IL-2 in
                          comparison with HAART alone on immune
                          reconstitution, specifically for increase in
                          CD4 count and duration of increase.
GENERAL DESCRIPTION       RATIONALE: One of the challenges in effective
                          combination therapy in HIV-infected patients
                          is the ability to achieve immune
                          reconstitution. IL-2 is hypothesized to
                          restore and/or preserve the immune system
                          when added to potent antiretroviral regimens.
                          This study will evaluate restoration of
                          immune functions of CD4 cells and will also
                          determine the best way to deliver IL-2 in a
                          safe and effective way.
GENERAL DESCRIPTION       METHODOLOGY: Part I: Patients add a 5-day
                          course of subcutaneous IL-2 every 8 weeks for
                          up to 48 weeks (6 cycles) to their HAART
                          therapy. Three dose levels of IL-2 are
                          administered. [AS PER AMENDMENT 5/3/01: It is
                          strongly recommended, but not required, that]
                          the first and second cycles of IL-2 are given
                          in the hospital on an inpatient basis. The
                          parent or patient is trained to give the
                          injections and has the option of
                          administering subsequent injections at home.
                          Patients are monitored for CD4 and CD8 cell
                          count and viral load. Enrollment into Part 1
                          begins at the lowest dose level; assuming no
                          serious toxicities (Grade 3 or higher) occur,
                          patients are enrolled into higher dose
                          levels. The highest tolerated dose is
                          established. Part 2: After the highest
                          tolerated dose is established in Part 1,
                          additional patients are randomized to receive
                          HAART alone (Arm 1), HAART with high-dose
                          IL-2 (Arm 2), or HAART with low-dose IL-2
                          (Arm 3). High-dose IL-2 is given twice daily
                          at the highest dose tolerated in Part 1 for 5
                          days every 8 weeks for 6 cycles. Low-dose
                          IL-2 is given once a day every day for 48
                          weeks. For Arms 2 and 3 [AS PER AMENDMENT
                          5/3/01: (except patients in the
                          pharmacokinetic substudy), it is strongly
                          recommended, but not required, that] IL-2 is
                          given the first week on an inpatient basis by
                          hospital personnel. As in Part 1, there is
                          the option of administering the remaining
                          injections at home. Intensive toxicity
                          monitoring, routine lymphocyte subsets, and
                          quantitative HIV RNA are performed on all
                          patients at specified time points during the
                          study. The first 12 patients in Arms 2 and 3
                          have pharmacokinetic testing with frequent
                          blood samples drawn at intervals, some of
                          which require staying up to 12 hours at the
                          clinic. Diphtheria/tetanus immunizations and
                          bacteriophage phi X174 immunizations are
                          administered to all patients to determine
                          antibody responses.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Immunotherapy, Maximum tolerated dose (MTD),
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 84 patients. Part 1 will
                          enroll 8 plus patients with sample size
                          contingent upon whether toxicities develop,
                          as defined by protocol. Part 2 will enroll
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks, with
                          possible extension to 96 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 6/84 010726.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 22
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010503)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 402
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Dose-Response Design
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection as documented by
                          positive culture or PCR on at least 2
                          occasions, or a positive ELISA and a
                          confirmatory Western blot. At least 1 of
                          these tests must be done in an ACTG-certified
                          laboratory that is approved to perform the
                          assay for protocol testing. 2. Plasma HIV RNA
                          of less than 10,000 copies/ml on 2
                          consecutive measurements of 30 days or less
                          apart. One measurement must be within 30 days
                          of study entry. One measurement must be
                          obtained by the Roche Amplicor Monitor assay
                          method; the other may be done by another
                          currently approved method. 3. Evidence of
                          immune suppression ([AS PER AMENDMENT 5/3/01:
                          defined as CDC Category 2 or 3, based on
                          age-specific CD4 cell counts and] an absolute
                          CD4 percentage less than 25 percent). 4.
                          Symptomatic HIV infection as defined by CDC
                          Category A, B, or C, except cardiomyopathy
                          and radiologic evidence of LIP which are not
                          allowed. 5. Consent of parent or guardian. 6.
                          Parent or guardian's willingness to comply
                          with study requirements.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 25 %.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN Adjusted for age.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN ULN (Upper Limit of
                          Normal). Adjusted for age.
PATIENT INCLUSION CRIT.   CREATININE: <= Age 2 to 13 years: <= 1.6
                          mg/dl; age 14 to 18 years: <= 2.4 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT TREATMENT: Allowed: 1.
                          Immunoglobulins for prophylaxis of VZV,
                          measles, or hepatitis B. Usage should be
                          strictly recorded. [2. AS PER AMENDMENT
                          5/3/01: Prophylactic administration of IVIG
                          started within 3 months of study entry.].
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Twelve or more
                          weeks of HAART prior to study entry,
                          consisting of at least 3 drugs, [AS PER
                          AMENDMENT 5/3/01: The following text has been
                          deleted: 1 of which must be a nonnucleoside
                          reverse transcriptase inhibitor (NNRTI), or a
                          protease inhibitor (PI); and has been
                          replaced with the following text: which may
                          include a nucleoside reverse transcriptase
                          inhibitor (NRTI), an NNRTI, or a PI, or 3
                          NRTIs. The combination of 3 NRTIs may not
                          include abacavir (ABC).].
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Antipyretics, antiemetics, antihistamines,
                          decongestants, skin creams and lotions,
                          antibiotics, and antiretrovirals. Usage
                          should be strictly recorded. 2. Children may
                          be immunized according to current
                          recommendations of the Advisory Committee on
                          Immunization Practice.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 02
                          years less than or equal to 18 years.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Prophylactic
                          administrations of immunoglobulin
                          preparations (IM or IV) except for
                          prophylaxis of VZV, measles, or hepatitis B.
                          [AS PER AMENDMENT 5/3/01: This is no longer
                          an exclusion.].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: [Excluded: AS PER AMENDMENT
                          5/3/01: 1. ABC as part of a 3 NRTI
                          combination. 2. Steroids or other
                          immunosuppressive therapy within 6 weeks
                          prior to study.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Steroids
                          or other immunosuppressive therapy. 2.
                          Polyclonal or monoclonal antibody therapy. 3.
                          Other immunomodulators. [4. AS PER AMENDMENT
                          5/3/01: ABC.].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Active
                          opportunistic infection.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0254  Bacteriophage phi X 174
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0312  Diphtheria and Tetanus
                          Toxoids Adsorbed
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0315  Tetanus and Diphtheria
                          Toxoids Adsorbed
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0324  Diphtheria & Tetanus
                          Toxoids &
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Part 1 - 2MIU/m2,
                          3MIU/m2, or 4MIU/m2 bid for 5 days evweeks
                          for 6 cycles. Part 2 - Arm 2, high-dose IL-2
                          (to be determined); Arm 3, 1.2MIonce a day.
                          Drug 2: Part 2 - 0.02 ml/kg at Weeks 12 and
                          18. Drug 3: Part 2 - (If less than 7 years
                          old and not taking Acel-Imune) Arms 1a, 2a,
                          and 3a, 0.5 ml at Week 4; Arms 1b, 2b,3b, 0.5
                          ml at Week 28. Drug 4: Part 2 - (If 7 years
                          old or more) Arms 1a, 2a, and 3a, ml at Week
                          4; Arms 1b, 2b, and 3b, 0.5 ml at Week 28.
                          Drug 5: Part 2 - (If less than 7 years old
                          and not taking DT-pediatric) Arms 1a, 2a, and
                          3a, 0.5 ml at Week 4; Arms 1b, 2and 3b, 0.5
                          ml at Week 28
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous. Drug 2:
                          Intravenous. Drug 3: Intramuscular. Drug 4:
                          Intramuscular. Drug 5: Intramuscular
OTHER TREATMENT INFO.     TREATMENT DURATION: Part 1: 48 weeks, with
                          option to extend to 96 weeks, based on
                          response. Part 2: 48 weeks, with option to
                          extend to 96 weeks.
OTHER TREATMENT INFO.     END POINT: Grade 3 or higher toxicity, except
                          fever and shaking.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Refusal of
                          further treatment and/or follow-up. 2.
                          Investigator determines that further
                          participation would be detrimental to
                          patient's health or well-being. 3.
                          Noncompliance. 4. Treatment requirement for
                          disallowed medications. 5. Drug toxicity
                          (Grade 3 or higher, except fever and
                          shaking). 6. Pregnancy. For premature
                          discontinuation and early withdrawal,
                          patients are asked to continue clinic visits.
OTHER TREATMENT INFO.     MODIFICATION: In Part 1 doses may be
                          decreased for Grades 1 and 2 toxicity with or
                          without interruption at each cycle, in
                          accordance with the protocol. In Part 2
                          unacceptable toxicity at the lowest dose
                          level will allow incremental dose reduction,
                          according to the protocol, to as low as 0.3
                          MIU/m2 given every other day. When a reduced
                          dose is tolerated, dosage may be increased
                          later at the discretion of the patient and
                          investigator.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 000713.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 000713.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Maryanne
                          Dillon [phone] Recruiting 000713.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 000724.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 001012.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 000713.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          000713.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 000713.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000713.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Bishop [phone] Recruiting 000713.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 010318.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 000713.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 001006.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 000713.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 000713.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 001013.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 000713.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 010423.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 000713.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          000713.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 000713.

84
UNIQUE IDENTIFIER         NIH/01253
PROTOCOL ID NUMBERS       NIAID ACTG A5001
PROTOCOL TITLE            Adult AIDS Clinical Trials Group Longitudinal
                          Linked Randomized Trials (ALLRT) Protocol.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Epidemiology
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine effective therapeutic
                          strategies or regimens that achieve long-term
                          suppression of HIV-1 replication to levels
                          below the limit of detection with the least
                          associated toxicity, as determined by the
                          future antiretroviral studies in which
                          patients co-enroll. To determine long-term
                          incidence rates, types, associated risk
                          factors, and clinical presentations of
                          HIV-related opportunistic and select
                          non-opportunistic complications of HIV
                          disease and associated treatment that occur
                          during potent antiretroviral therapy; also,
                          to compare these clinical outcomes for
                          patients who have long-term suppression of
                          plasma HIV-1 RNA levels with those of
                          patients with lesser degrees or shorter
                          durations of suppression of HIV-1 replication
                          (virologic success vs virologic failure).
                          To determine the factors that are associated
                          with the degree of immunologic restoration
                          during antiretroviral therapy.
GENERAL DESCRIPTION       RATIONALE: Based on present and recently
                          completed studies, a compilation of outcomes
                          of various therapies would be beneficial when
                          evaluating which strategies are most
                          effective in long-term treatment of HIV-1.
                          This study will correlate therapies with the
                          achievement of, or maintenance of, durable
                          suppression of HIV-1 replication to levels
                          below the limit of detection.
GENERAL DESCRIPTION       METHODOLOGY: No treatment is provided by this
                          study, but patients continue with
                          antiretroviral therapy from other studies in
                          which they are co-enrolled. Blood specimens
                          are collected at study entry and every 16
                          weeks over a 4-year period to monitor
                          virologic and immunologic outcomes. Pelvic
                          exams and Pap smears may be done for women.
                          Portions of blood samples will be stored to
                          evaluate genotypic/phenotypic susceptibility
                          testing. Medical histories, physical exams,
                          and questionnaires are done periodically for
                          long-term clinical assessment. The
                          immunologic and clinical outcomes and
                          complications associated with the success or
                          failure of prolonged use of potent
                          antiretroviral therapies will be examined.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy,
                          Immunology, Strategy determination, Viral
                          load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 3000 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4-6 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1613/3000 010731.
PROTOCOL DETAILS          STUDY DURATION: 6 years, or 4 years after the
                          anticipated 2-year accrual.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 58
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (991130)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5001
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Longitudinal
                          Study; Meta-Analysis
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Current participation in an approved
                          parent AACTG study or completed an approved
                          parent AACTG study within the past 8 weeks.
                          Patients planning to enter a parent AACTG
                          study must be randomized/registered to the
                          parent protocol prior to registration to the
                          ALLRT protocol. Patients off study treatment
                          but who remain on study follow-up in the
                          parent protocol will be allowed to enroll. 2.
                          HIV-1 infection as documented by the approved
                          AACTG parent protocol. 3. Willingness to
                          allow ALLRT protocol team access to and use
                          of data from AACTG clinical trial databases
                          and clinic records generated on the parent
                          study and other co-enrolled AACTG protocols.
                          4. Consent of parent or guardian if under 18.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following are excluded: 1. Life expectancy
                          less than 24 weeks. 2. Other factors, at the
                          discretion of the local investigator, that
                          could prevent compliance with study visits.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active substance
                          abuse that could prevent compliance.
OTHER TREATMENT INFO.     END POINT: Antiretroviral therapy and
                          virology analyses; complications of HIV
                          disease (clinical) analyses; and immunology
                          analyses.
OTHER TREATMENT INFO.     DISCONTINUE: No treatment will be provided by
                          the study, but study discontinuation criteria
                          are as follows: 1. Failure without reasonable
                          cause to attend three consecutive ALLRT
                          clinic visits. 2. Patient requests
                          withdrawal. 3. Investigator believes such
                          action is warranted.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 000317.
CALIFORNIA                Kaiser Permanente LAMC 1505 N Edgemont St /
                          Second Floor Los Angeles, CA 90027 Mitzi St
                          Ange [phone] Recruiting 001129.
CALIFORNIA                Marin County Specialty Clinic 161 Mitchell
                          Building Suite 200 San Rafael, CA 94903 Marc
                          Gould [phone] Recruiting 000210.
CALIFORNIA                Univ of California / San Diego Treatment Ctr
                          2760 5th Ave / Suite 300 San Diego, CA
                          921036325 Jill Kunkel [phone]
                          Recruiting 000327.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 000203.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 000614.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 000327.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          000210.
CALIFORNIA                Santa Clara Valley Med Ctr / AIDS Community
                          Rsch Consortium 751 South Bascom Ave San
                          Jose, CA 951282699 Debbie Slamowitz
                          [phone] Recruiting 000419.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 000203.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Sally Kruger [phone]
                          Recruiting 000228.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 000203.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000327.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone]
                          Recruiting 000228.
GEORGIA                   Emory Hemo Comp Evaluation Clinic / East TN
                          Comp Hemo Ctr 550 Peachtree St NE Atlanta, GA
                          303652225 Judy Powers [phone]
                          Recruiting 000614.
GEORGIA                   Emory Univ 341 Ponce de Leon Ave Atlanta, GA
                          30308 Beth Dean [phone] Recruiting
                          000228.
HAWAII                    Tripler Army Med Ctr Infectious Disease
                          Services MCHK-DMI / One Jarrett White Rd
                          Tripler AMC, HI 96859 Ross Newmann
                          [phone] Recruiting 000815.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          000210.
IOWA                      Univ of Iowa Hosp and Clinic 200 Hawkins Dr
                          Iowa City, IA 52242 Julie Katseres
                          [phone] Recruiting 000310.
ILLINOIS                  Cook County Hosp 637 South Wood Chicago, IL
                          60612 Edward Goodwin [phone] Recruiting
                          000317.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Jan
                          Fritsche [phone] Recruiting 000502.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 000210.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 000310.
INDIANA                   Division of Inf Diseases/ Indiana Univ Hosp
                          1001 West 10th St / OPW 430 Indianapolis, IN
                          46202 Beth Zwickl [phone] Recruiting
                          000310.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 000310.
LOUISIANA                 Tulane Med Ctr Hosp 1415 Tulane Ave New
                          Orleans, LA 70112 Eric Horman [phone]
                          Recruiting 000531.
MASSACHUSETTS             Harvard (Massachusetts Gen Hosp) 55 Fruit St
                          / Founders Bldg 8th Floor Boston, MA 02114
                          Teri Flynn [phone] Recruiting 000127.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 000228.
MASSACHUSETTS             Brigham and Women's Hosp 75 Francis St /
                          Children's Hosp AIDS Program Boston, MA 02115
                          Teri Flynn [phone] Recruiting 000419.
MASSACHUSETTS             Boston Med Ctr 1 Boston Med Ctr Place /
                          Dowling Bldg Boston, MA 02118 Caress Grodman
                          [phone] Recruiting 000419.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Rebecca Becker
                          [phone] Recruiting 010723.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 000327.
MISSOURI                  St Louis Regional Hosp / St Louis Regional
                          Med Ctr 5535 Del Mar / West Annex / 6th Floor
                          St Louis, MO 63112 Michael Klebert
                          [phone] Recruiting 000210.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 000228.
NORTH CAROLINA            Moses H Cone Memorial Hosp 1200 North Elm St
                          Greensboro, NC 27401 Pam Mentley
                          [phone] Recruiting 000310.
NORTH CAROLINA            Carolinas Med Ctr 1000 Blythe Blvd / MEB 202
                          Charlotte, NC 28203 Marjorie Massey
                          [phone] Recruiting 000424.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Barbara
                          Longmire [phone] Recruiting 000228.
NEBRASKA                  Univ of Nebraska Med Ctr 985130 Nebraska Med
                          Ctr Omaha, NE 681985130 Frances Van Meter
                          [phone] Recruiting 000228.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 000127.
NEW YORK                  Community Health Network Inc Univ of
                          Rochester Med Center / 601 Elmwood Ave
                          Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 000502.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 001012.
NEW YORK                  Aaron Diamond AIDS Rsch Ctr / Rockefeller
                          Univ 1230 York Ave New York, NY 10021 Arlene
                          Hurley [phone] Recruiting 010702.
NEW YORK                  SUNY / Erie County Med Ctr at Buffalo 462
                          Grider Street Buffalo, NY 14215 Ross Hewitt
                          [phone] Recruiting 000410.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] Recruiting 000609.
NEW YORK                  Chelsea Ctr Cornell Univ Clinical Trials Unit
                          / 525 East 68th St New York, NY 10021 Brenda
                          Greenhill [phone] Recruiting 000524.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 000228.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 000228.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Brenda Greenhill [phone]
                          Recruiting 000524.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 000310.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 000210.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Nancy Frantz
                          [phone] Recruiting 000127.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 000327.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          000310.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000424.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 000210.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] No longer recruiting 010222.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 000531.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 000228.

85
UNIQUE IDENTIFIER         NIH/01251
PROTOCOL ID NUMBERS       NIAID ACTG A5043
PROTOCOL TITLE            Pharmacokinetic Interaction Studies of
                          Amprenavir (APV), Efavirenz (EFV), and a
                          Second Protease Inhibitor in HIV-Seronegative
                          Volunteers.
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: 1. To examine the pharmacokinetics
                          (PK) of amprenavir (APV) when taken under 6
                          conditions: 1) alone, 2) with efavirenz
                          (EFV), 3) with EFV plus nelfinavir (NFV), 4)
                          with EFV plus indinavir (IDV), 5) with EFV
                          plus ritonavir soft gel capsules (RTV sgc),
                          and 6) with EFV plus saquinavir soft gel
                          capsules (SQV sgc). 2. To compare the PK of
                          EFV when taken under 5 conditions: 1) with
                          APV, 2) with APV plus NFV, 3) with APV plus
                          IDV, 4) with APV plus RTV (sgc), and 5) with
                          APV plus SQV (sgc).
GENERAL DESCRIPTION       RATIONALE: Triple-drug antiretroviral
                          regimens have become the recommended approach
                          to therapy for HIV infection. [AS PER
                          AMENDMENT 12/4/00: The clinical use of
                          multiple-drug antiretroviral regimens
                          containing various combinations of nucleoside
                          reverse transcriptase inhibitors (NRTIs),
                          nonnucleoside reverse transcriptase
                          inhibitors (NNRTIs), and protease inhibitors
                          (PIs) has become a widespread approach to
                          therapy for HIV infection, especially for
                          patients previously treated with PIs.] Since
                          the introduction of PIs, a greater awareness
                          of the relationship between optimal
                          suppression of viral replication, genotypic
                          resistance, and viral rebound has led to the
                          design of more potent antiretroviral drug
                          combinations. Two ACTG clinical trials
                          addressing the issue of virologic failure
                          utilize antiviral regimens that include 2
                          NRTIs, 2 PIs (one of which is APV), and EFV
                          (NNRTI). Although this drug combination is
                          logical, there is limited PK data to guide
                          the dosing selection. This study enrolls
                          healthy volunteers to obtain PK profiles and
                          metabolic assessments of APV/EFV before and
                          after the addition of a second PI [AS PER
                          AMENDMENT 12/4/00: APV alone, APV combined
                          with EFV, and APV/EFV combined with a second
                          PI].
GENERAL DESCRIPTION       METHODOLOGY: Upon study entry, volunteers
                          receive APV plus EFV for 2 weeks. [AS PER
                          AMENDMENT 12/4/00: Volunteers receive a
                          single dose of APV alone on Day 0, EFV alone
                          on Days 1 to 10, and APV combined with EFV on
                          Days 11 to 13.] After 2 weeks [AS PER
                          AMENDMENT 12/4/00: After completion of the
                          second PK visit], volunteers are randomized
                          to 1 of 5 treatment arms to add a second PI
                          to the APV/EFV drug combination for 2 more
                          weeks [AS PER AMENDMENT 12/4/00: for at least
                          1 week]. The treatment arms are as follows:
                          Arm A (control arm): APV and EFV alone. Arm
                          B: APV and EFV plus IDV [AS PER AMENDMENT
                          12/4/00: APV and EFV plus NFV]. Arm C: APV
                          and EFV plus NFV [AS PER AMENDMENT 12/4/00:
                          APV and EFV plus IDV]. Arm D: APV and EFV
                          plus RTV sgc. Arm E: APV and EFV plus SQV
                          sgc. On Day 14, 15, or 16, volunteers return
                          to the clinic for PK testing following the
                          dual-drug regimen, and again on Day 29, 30,
                          or 31 following the triple-drug regimen (or
                          continued dual-drug regimen for Arm A). [AS
                          PER AMENDMENT 12/4/00: Volunteers attend
                          clinics for PK testing on Days 0 and 1 (first
                          visit), after taking the dual-drug regimen
                          for at least 3 days (second visit, e.g., on
                          Day 14 or after), and after taking the
                          triple-drug regimen (or, if in Arm A, after
                          continuing on the dual-drug regimen) for at
                          least 7 days (third visit).] Before each PK
                          testing, volunteers complete an Adherence
                          Questionnaire. [AS PER AMENDMENT 12/4/00: The
                          Adherence Questionnaire is administered at
                          the second and third PK visits.] Volunteers
                          maintain a food diary. Two to three weeks
                          after completing the drug regimen [AS PER
                          AMENDMENT 12/4/00: Within 2-3 weeks after the
                          third PK visit], volunteers return to the
                          clinic for evaluations and urine and blood
                          sampling.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Adverse effects, Combination
                          pharmacokinetics, Drug safety,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients. 14 volunteers
                          will be enrolled in each of five arms. [AS
                          PER AMENDMENT 12/4/00: 70 evaluable
                          volunteers (14 per arm) will be accrued.] For
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4 weeks [AS PER
                          AMENDMENT 12/4/00: 3 weeks] of drug
                          administration, and a follow-up visit 2 to 3
                          weeks post-treatment [AS PER AMENDMENT
                          12/4/00: within 2 to 3 weeks after the third
                          PK visit].
PROTOCOL DETAILS          ACTUAL ACCRUAL: 11/90 010712.
PROTOCOL DETAILS          STUDY DURATION: 7 weeks. [AS PER AMENDMENT
                          12/4/00: 6 months.].
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 10
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (001204)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Seronegativity.
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Concentration-Response Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must
                          have: 1. HIV-1 seronegativity as documented
                          by any licensed ELISA test kit within 21 days
                          of study entry. 2. No reproductive potential,
                          if a woman, defined as post-menopausal or
                          surgically sterile by hysterectomy, bilateral
                          oophorectomy, or tubal ligation as documented
                          by medical records.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: Within normal limits.
PATIENT INCLUSION CRIT.   PLATELET COUNT: Within normal limits.
PATIENT INCLUSION CRIT.   BILIRUBIN: Within normal limits.
PATIENT INCLUSION CRIT.   SGOT(AST): Within normal limits.
PATIENT INCLUSION CRIT.   SGPT(ALT): Within normal limits.
PATIENT INCLUSION CRIT.   CREATININE: Within normal limits.
PATIENT INCLUSION CRIT.   OTHER: CBC including white blood cell count
                          (WBC) with differential, creatine
                          phosphokinase (CPK), albumin, serum amylase,
                          and urinalysis with microscopic examination,
                          all within normal limits.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: No future reproduction
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after.
PATIENT INCLUSION CRIT.   WEIGHT: Included: 50 kg or greater, and
                          volunteer is within 20% of ideal body weight.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Aspirin or
                          acetaminophen as an analgesic and
                          diphenhydramine as a sleeping aid.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 65 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Volunteers with
                          the following are excluded: 1. History of
                          cardiovascular, renal, hematologic,
                          neurologic, gastrointestinal, psychiatric,
                          endocrine, or immunologic diseases, including
                          the following: hypertension, coronary artery
                          disease, arthritis, diabetes, any chronic
                          gastrointestinal conditions that might
                          interfere with drug absorption, and
                          depression. 2. Documented or suspected acute
                          hepatitis within 35 days of study entry,
                          regardless of AST (SGOT) and ALT (SGPT)
                          values that are within the laboratory's
                          normal limits. 3. Unexplained temperature
                          greater than 38.5 C or any febrile illness
                          lasting for 7 or more days [AS PER AMENDMENT
                          12/4/00: 3 or more days] within 14 days of
                          study entry. 4. History of hypersensitivity
                          to any of the study medications or their
                          excipients (e.g., gelatin or fillers). 5.
                          Reproductive potential (women).
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: 1. Active substance
                          abuse that, in the opinion of the
                          investigator, would interfere with study
                          adherence. 2. Changes in existing tobacco
                          smoking habits for the duration of the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Investigational agents within 35 days of
                          study entry. 2. Acute therapy for an
                          infection or other medical illness within 14
                          days of study entry. 3. Chronic or
                          prescription medications within 14 days of
                          study entry such as prednisone or any other
                          corticosteroids (due to the effect on glucose
                          metabolism) as well as growth hormone,
                          megestrol acetate, testosterone,
                          hormone-replacement therapy (estrogens and
                          progesterones), dexamethasone,
                          anabolic-androgenic steroids, and
                          androstenedione. Non-chronic,
                          over-the-counter drugs may be taken as needed
                          up to 48 hours prior to study entry. 4.
                          Natural or homeopathic remedies within 14
                          days of study entry. 5. Antidepressant
                          medications, e.g., Prozac.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Caffeine
                          use during the first 5 hours of sample
                          collection on pharmacokinetic evaluation
                          days. 2. Alcohol intake the day prior to and
                          day of pharmacokinetic evaluation. 3.
                          Nutritional supplements such as chromium
                          picolinate, DHEA, DHEA-sulfate, creatine
                          (monohydrate), protein/amino acid powders,
                          medium-chain triglycerides (MCT), omega-3
                          fatty acids [AS PER AMENDMENT 12/4/00: and
                          St. John's wort]. A daily multivitamin and
                          mineral supplement is permitted. 4. Any
                          non-protocol specified drug, licensed or
                          investigational. 5. Vitamin E supplementation
                          (except for a daily multivitamin). 6.
                          Compazine within 4 days of PK testing.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Volunteers with the following
                          symptoms or conditions are excluded: 1.
                          Cardiovascular, renal, hematologic,
                          neurologic, gastrointestinal, psychiatric,
                          endocrine, or immunologic diseases, including
                          the following: hypertension, coronary artery
                          disease, arthritis, diabetes, any chronic
                          gastrointestinal conditions that might
                          interfere with drug absorption, and
                          depression. 2. Medical condition that, in the
                          opinion of the investigator, would interfere
                          with the ability to participate in the
                          protocol, including asthma, high [AS PER
                          AMENDMENT 12/4/00: elevated] cholesterol,
                          high [AS PER AMENDMENT 12/4/00: elevated]
                          triglycerides, pancreatitis, and
                          blood-clotting disorders that would confound
                          the metabolic testing. 3. Inability to be
                          adherent with the study medications during
                          the study period. 4. Inability to participate
                          in the pharmacokinetic study periods. 5.
                          Inability to abstain from high-impact or
                          strenuous exercise for study duration. 6.
                          Allergic reaction to sulfa drugs or
                          anaphylaxis to any other drug.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0244  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0164  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0269  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0258  Saquinavir
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0263  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0233  Amprenavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm D: 200 mg [AS
                          PER AMENDMENT 12/4/00: 100 mg] bid. Drug 2:
                          Arm E: 1600 mg bid. Drug 3: Arms A, B, C, D,
                          and E: 600 mg qd. Drug 4: Arms A, B, C, and
                          E: 1200 mg [AS PER AMENDMENT 12/4/00:mg] bid.
                          Arm D: 600 mg bid. Drug 5: Arm C [AS PER
                          AMENDMENT 12/4/00: Arm B]: 1250 mg bid. Drug
                          6: Arm B [AS PER AMENDMENT 12/4/00: Arm C]:
                          1200 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Arm D: 400 mg [AS PER
                          AMENDMENT 12/4/00: 200 mg]. Drug 2: Arm E:
                          3200 mg. Drug 3: Arms A, B, C, D, and E: 600
                          mg. Drug 4: Arms A, B, C, and E: 2400 mg. [AS
                          PER AMENDMENT 12/4/01200 mg.] Arm D: 1200 mg.
                          Drug 5: Arm C [AS PER AMENDMENT 12/4/00: Arm
                          B]: 2500 mg. Drug 6: Arm B [AS PER AMENDMENT
                          12/4/00: Arm C]: 2400 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 100 mg soft gel
                          capsules. Drug 2: Oral, 200 mg soft gel
                          capsules. Drug 3: Oral, 200 mg capsules. Drug
                          4: Oral, 150 mg capsules. Drug 5: Oral, 250
                          mg tablets. Drug 6: Oral, 200 mg capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 weeks. [AS PER
                          AMENDMENT 12/4/00: 3 weeks.].
OTHER TREATMENT INFO.     END POINT: Pharmacokinetic measurements of
                          APV and EFV, and adverse reactions with Grade
                          2 or higher severity, as defined by the DAIDS
                          Toxicity Tables.
OTHER TREATMENT INFO.     DISCONTINUE: Volunteers discontinue treatment
                          for the following reasons: 1. Drug-related
                          toxicities of Grade 2 or higher. 2.
                          Volunteer's request. 3. Investigator deems
                          study medications are life-threatening even
                          though toxicity classification in protocol is
                          not met. 4. Requirement for
                          protocol-disallowed concomitant medication.
                          5. Noncompliance. [6. AS PER AMENDMENT
                          12/4/00: Any signs of rash, regardless of
                          grade.] Note: In the event of
                          discontinuation, a volunteer is asked to
                          return to the clinic within 7 days of
                          stopping study drugs so that information
                          about drug effects can be gathered.
OTHER TREATMENT INFO.     MODIFICATION: Volunteers are closely
                          monitored for signs and symptoms of drug
                          toxicity. There will be no dose
                          interruptions, modifications, or
                          discontinuations for volunteers experiencing
                          Grade 1 toxicity. For Grade 2 and higher
                          toxicities, study medications must be
                          permanently discontinued.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 000203.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010222.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000310.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          010323.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 000317.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 000210.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 010323.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 010423.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 010702.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 010301.

86
UNIQUE IDENTIFIER         FDA/01245
PROTOCOL ID NUMBERS       FDA 246U
PROTOCOL TITLE            A Multicenter, Open-Label, 24-Week Pilot
                          Study to Evaluate the Safety and Activity of
                          Indinavir Sulfate 1200 mg q.d. and Ritonavir
                          200 mg q.d. in Combination With Stavudine and
                          Lamivudine in Treatment Naive HIV-1 Infected
                          Patients.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and
                          tolerability of indinavir (IDV) and ritonavir
                          (RTV) when administered in combination with
                          stavudine (d4T) and lamivudine (3TC) to
                          treatment-naive HIV-infected patients. To
                          determine the proportion of patients
                          achieving plasma viral RNA levels less than
                          400 copies/ml at Week 24.
GENERAL DESCRIPTION       RATIONALE:
GENERAL DESCRIPTION       METHODOLOGY: Patients entering this study
                          initiate antiretroviral therapy. For 24 weeks
                          patients receive daily dosages of IDV, RTV,
                          3TC, and d4T. Patients are seen at Day 1 and
                          at Weeks 2, 4, 8, 12, 16, 20, and 24 for
                          physical examinations, pregnancy testing, and
                          blood sampling to monitor CD4 count and viral
                          load. On Day 14, blood is drawn frequently
                          for 24 hours for IDV and RTV pharmacokinetic
                          sampling. The incidence of serious and
                          drug-related adverse events and of adverse
                          events leading to study discontinuation is
                          tabulated.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (991223)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy,
                          Combination pharmacokinetics, Drug efficacy,
                          Drug safety, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 8 patients. 8 patients
                          with conditional expansion to 40.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/8.
PROTOCOL DETAILS          STUDY DURATION: 24 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3
PROTOCOL DETAILS          VERSION NUMBER & DATE: (990818)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: 104-00
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Concentration-Response Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection. 2. CD4 count of 50
                          cells/mm3 or greater. 3. Plasma viral RNA
                          level of at least 5,000 copies/ml.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 50 cells/mm3.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Therapy with any
                          antiretroviral agent.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 30 mg bid if body
                          weight is less than 60 kg; 40 mg bid body
                          weight is 60 kg or higher. Drug 2: 150 mg
                          bid. Drug 3: 1200 mg qd. Drug 4: 200 mg qd
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 60 mg if patient weighs
                          less than 60 kg; 80 mg if patieweighs 60 kg
                          or higher. Drug 2: 300 mg. Drug 3: 1200 mg.
                          Drug 4: 200 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral, 15-, 20-, 30-,
                          or 40-mg capsules. Drug 2: Oral, 150-mg
                          tablets. Drug 3: Oral, 400-mg capsules. Drug
                          4: Oral, 100-mg soft-gel capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
SUPPORTING AGENCY         Merck & Co Inc.
LAST REVISION DATE        19991223
FLORIDA                   Univ of Miami School of Medicine 1600 NW 10th
                          Ave Miami, FL 33136 Tom Tanner [phone]
                          Recruiting 000111.
NEW YORK                  SUNY at Stony Brook / Division of Infectious
                          Diseases HSCT15 / Room 080 Stony Brook, NY
                          11794 Ruth Tenzler [phone] Recruiting
                          000111.
NEW YORK                  Albany Med College 47 New Scotland Ave / MC
                          142 Albany, NY 12208 Sandra Preston
                          [phone] Recruiting 000111.

87
UNIQUE IDENTIFIER         NIH/01244
PROTOCOL ID NUMBERS       NIAID DAIDS R001
PROTOCOL TITLE            A Pilot, Proof-of-Concept, Dose-Escalating
                          Trial of Recombinant Human Interleukin-12
                          (rhIL-12) Versus Placebo Along with
                          Paromomycin and Azithromycin for Chronic
                          Cryptosporidiosis in AIDS.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To assess the safety of the
                          combination of interleukin-12 (IL-12),
                          paromomycin, and azithromycin in AIDS
                          patients with chronic cryptosporidiosis. To
                          compare the efficacy of IL-12 in combination
                          with paromomycin and azithromycin versus the
                          combination of paromomycin and azithromycin
                          without IL-12 in the treatment of AIDS
                          patients with chronic cryptosporidiosis.
GENERAL DESCRIPTION       RATIONALE: Cryptosporidium parvum, an
                          intracellular protozoan parasite, is a
                          frequent cause of chronic diarrhea in
                          HIV-infected patients, causing significant
                          morbidity and mortality. Highly effective
                          antiparasitic treatment for this infection is
                          not currently available. Paromomycin and
                          azithromycin have some efficacy and have been
                          used in combination in a small number of
                          patients. Immune reconstitution with highly
                          active antiretroviral therapy appears to be
                          the most effective therapy, but this is not
                          possible for all patients. Interferon gamma
                          expression is strongly associated with
                          control of cryptosporidiosis, and IL-12 is
                          the cytokine primarily responsible for
                          stimulation of interferon gamma expression in
                          vivo. It is hoped that treatment with
                          recombinant human IL-12 can result in
                          stimulation of an intestinal cytokine
                          response in AIDS patients with
                          cryptosporidiosis and that response combined
                          with chemotherapy can lead to the elimination
                          of detectable numbers of Cryptosporidium
                          oocysts from the stools.
GENERAL DESCRIPTION       METHODOLOGY: All patients receive
                          azithromycin and paromomycin, and patients
                          are randomized to add either IL-12 or
                          placebo. IL-12 (or placebo) injections are
                          given twice a week. Patients take their study
                          medications for 4 weeks. During this time,
                          they will be asked to record bowel movements
                          and any symptoms they experience. Patients
                          return to the clinic at least twice a week to
                          receive IL-12 (or placebo) injections. At
                          Weeks 2 and 4, patients are seen by one of
                          the principal investigators. Blood samples
                          are obtained for viral load measurements and
                          CD4 count, as well as routine urinalysis.
                          Patients undergo upper endoscopy with jejunal
                          biopsy and colonoscopy with ileal biopsy
                          between Weeks 2 and 4 of therapy for assays
                          of intestinal cytokine expression. A final
                          clinic visit occurs 12 weeks post-therapy for
                          a physical exam and blood tests.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (001121)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 16 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4 weeks plus 1
                          year of follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/16.
PROTOCOL DETAILS          VERSION NUMBER & DATE: (990401)
PROTOCOL DETAILS          DISEASE STUDIED: Cryptosporidiosis.
PROTOCOL DETAILS          STUDY DESIGN: Double-Blind Method;
                          Dose-Response Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 cell counts
                          below 150 cells/microl. 3. Chronic diarrhea
                          defined as three bowel movements a day that
                          are loose or watery, for 5 days per week over
                          3 weeks. 4. Stool positive for
                          Cryptosporidiosis and no other enteric
                          pathogen (bacterial culture, C. difficile
                          toxin assay, AFB stain, ova and parasite
                          examination, and stain for microsporidia).
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 150 cells/microL.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x ULN Unless the elevation is
                          felt to be due to indinavir.
PATIENT INCLUSION CRIT.   SGOT(AST): < 2.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 2.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable
                          antiretroviral regimen that includes at least
                          two nucleoside analogues for at least 4
                          weeks. (This includes patients who have not
                          or will no longer respond to therapy with HIV
                          protease inhibitors or those that are not
                          able to begin protease inhibitor therapy for
                          4 weeks, for example, due to concomitant
                          tuberculosis therapy or administrative delay
                          in securing protease inhibitors.).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hypersensitivity or significant
                          intolerance to aminoglycosides, macrolide
                          antibiotics, or colony stimulating factors.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Other known or suspected active opportunistic
                          infection. 2. Requirement for intravenous
                          fluids.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0259  Interleukin-12
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0104  Azithromycin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0188  Paromomycin sulfate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 100 or 300 ng/kg
                          twice a week. Drug 2: 600 mg qd. Drug 3: 1.0
                          g bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 2: 600 mg. Drug 3: 2.0 g
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous
                          injection. Drug 2: Oral. Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 weeks plus 1 year of
                          follow-up.
OTHER TREATMENT INFO.     END POINT: Safety of the combination regimen,
                          eradication of oocyst excretion (as measured
                          by immunofluorescence and intestinal biopsy),
                          and decreases in oocyst excretion by
                          quantitative immunofluorescent antibody test
                          or stool biopsy.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20001121

88
UNIQUE IDENTIFIER         NIH/01239
PROTOCOL ID NUMBERS       NIAID ACTG A5062
PROTOCOL TITLE            Viral and Immune Dynamics in HIV-Infected
                          Patients with Tuberculosis.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To determine whether HIV RNA
                          clearance is influenced by tuberculosis (TB)
                          in patients initiating highly active
                          antiretroviral therapy (HAART). To determine
                          whether the recovery of T lymphocyte
                          populations and functions are influenced by
                          TB in subjects initiating HAART.
GENERAL DESCRIPTION       RATIONALE: Previous studies have focused on
                          characterizing viral and immune dynamics
                          after initiation of HAART in patients without
                          opportunistic infection. The development of
                          TB in HIV-infected individuals is associated
                          with an elevation in HIV RNA levels, a
                          decrease in CD4 cell counts, and an increase
                          in activated (CD38) lymphocytes and
                          proinflammatory cytokines (IL-1, TNF-alpha,
                          and IL-6). Response to HAART may differ in
                          individuals with an active opportunistic
                          infection such as TB.
GENERAL DESCRIPTION       METHODOLOGY: HIV-infected patients with
                          active TB follow an anti-TB regimen including
                          rifabutin and are observed for a maximum of
                          24 weeks before they initiate HAART. Plasma
                          samples for 24-hour post-rifabutin dosing are
                          collected at entry and at Weeks 4, 8, and 12,
                          then again at Weeks 2, 3, 4, 12, and 24 after
                          HAART initiation. Analyses of these samples
                          are used to explore the relationship between
                          cytokines and rifabutin metabolism and the
                          effect of nelfinavir on rifabutin
                          pharmacokinetics. The HAART regimen is
                          nelfinavir plus lamivudine (3TC) plus either
                          zidovudine (ZDV) or stavudine (d4T). After
                          initiation of HAART, all patients undergo
                          intensive monitoring of viral and immune
                          dynamics for 2 months. The patients continue
                          to be followed for 1 year from the time of
                          starting HAART. Neither the HAART drug
                          regimen nor anti-TB medications will be
                          provided by the study and must be obtained by
                          prescription. If patients are intolerant of
                          the HAART regimen or exhibit virologic
                          rebound, primary providers can alter or
                          modify this regimen. As part of substudy
                          A5065s, patients who experience signs or
                          symptoms of paradoxical reactions (i.e., new
                          persistent fevers that develop after
                          initiating HAART and which last for more than
                          1 week without an identifiable source; marked
                          worsening or emergence of intrathoracic
                          lymphadenopathy, pulmonary infiltrates;
                          worsening or emergence of cervical adenopathy
                          on serial physical examinations; or worsening
                          of other tuberculous lesions) have additional
                          clinical evaluations (including a chest
                          x-ray, a target clinical assessment,
                          concomitant medications, and signs and
                          symptoms) weekly for 4 weeks, then every
                          month thereafter until the symptoms resolve.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 44 patients. 14 in the
                          control group and 30 in the TB-infected
                          group.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to one and a
                          half years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 8/44 010420.
PROTOCOL DETAILS          STUDY DURATION: Up to one and a half years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (991110)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5062
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Case-Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA.
                          2. HIV-1 RNA plasma viral load of at least
                          20,000 copies/ml within 30 days of study
                          entry. 3. Candidate status for initiating
                          antiretroviral regimen of ZDV (or d4T), 3TC,
                          and nelfinavir. Patients in the control group
                          must have: No clinical or radiologic evidence
                          of active TB. Patients in the TB treatment
                          group must have one of the following: Newly
                          diagnosed TB confirmed by culture or Rapid
                          Diagnostic Amplification Test obtained within
                          16 weeks of enrollment, or suspected TB based
                          on a compatible clinical picture, a positive
                          smear for mycobacteria from a respiratory
                          secretion, a mycobacterial culture (results
                          of which are pending), and initiation of
                          empiric TB therapy.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: < Grade 3.
PATIENT INCLUSION CRIT.   SGOT(AST): < Grade 3.
PATIENT INCLUSION CRIT.   SGPT(ALT): < Grade 3.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70 within 14 days of study
                          entry.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry Abstinence or effective method of
                          birth control / contraception including oral
                          contraceptives during the study Not pregnant.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required for patients in
                          the TB treatment group: Rifabutin-containing
                          TB regimen recommended by the CDC
                          Tuberculosis Treatment Consortium Protocol
                          beginning at least 2 weeks before initiation
                          of HAART and directly observed therapy as an
                          outpatient.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required for patients
                          in the TB treatment group : 1.
                          Rifabutin-containing TB regimen recommended
                          by the CDC Tuberculosis Treatment Consortium
                          Protocol beginning at least 2 weeks before
                          initiation of HAART and directly observed
                          therapy as an outpatient. 2. HAART to be
                          initiated within 6 months of initiation of TB
                          therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: All patients:
                          Combination antiretroviral therapy for
                          greater than 3 months. Patients in TB
                          treatment group: 1. HAART during episode of
                          TB. 2. More that 16 weeks of TB therapy for
                          the present episode.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Life
                          expectancy less than 1 year. Patients in the
                          TB treatment group with the following
                          symptoms or conditions are excluded: 1.
                          Suspected multidrug-resistant TB. 2.
                          Inability to switch from rifampin to
                          rifabutin at least 2 weeks prior to
                          initiating HAART.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0085  Rifabutin
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0111  Ethambutol hydrochloride
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 5: Induction phase:
                          Daily for 8 weeks or daily for 2 weeks and
                          then two times/week weeks. Continuation
                          phase: Daily or two times/week for 18 weeks.
                          Drug 6: Induction phase: Daily for 8 weeks or
                          daily for 2 weeks and then two times/week
                          weeks
OTHER TREATMENT INFO.     DISCONTINUE: Patients may be discontinued for
                          the following reasons: 1. Request by the
                          patient to withdraw at any time for any
                          reason. 2. The investigator feels that
                          continued participation in the study may be
                          harmful to the patient. 3. Pregnancy.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of California / San Diego Treatment Ctr
                          2760 5th Ave / Suite 300 San Diego, CA
                          921036325 Jill Kunkel [phone]
                          Recruiting 000228.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 001122.
ILLINOIS                  Cook County Hosp 637 South Wood Chicago, IL
                          60612 Edward Goodwin [phone] Recruiting
                          000524.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 000502.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 000310.
NEW YORK                  Columbia Presbyterian Med Ctr Harkness
                          Pavilion 6 Room 644 / 622 West 168th Street
                          New York, NY 10032 Mykyelle Crawford
                          [phone] Recruiting 000726.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000410.
TENNESSEE                 Vanderbilt Univ Med Ctr Division of
                          Infectious Diseases / 345 24th Avenue North
                          Nashville, TN 37203 Victoria Harris
                          [phone] Recruiting 010612.

89
UNIQUE IDENTIFIER         NIH/01238
PROTOCOL ID NUMBERS       NIAID ESPRIT 001
PROTOCOL TITLE            A Randomized, Open-Label, Phase III,
                          International Study of Subcutaneous
                          Recombinant IL-2 (Proleukin) in Patients with
                          HIV-1 Infection and CD4+ Cell Counts Greater
                          than or Equal to 300/mm3: Evaluation of
                          Subcutaneous Proleukin in a Randomized
                          International Trial (ESPRIT).
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To compare the effects of
                          subcutaneous recombinant interleukin-2 (SC
                          rIL-2) and no SC rIL-2 on disease progression
                          [AS PER AMENDMENT 12/15/00: (new and
                          recurrent events)] and death over a 5-year
                          follow-up period in patients with HIV-1
                          infection and absolute CD4 cell counts of at
                          least 300 cells/mm3 who are taking
                          combination antiretroviral therapy.
GENERAL DESCRIPTION       RATIONALE: Much progress has been made in
                          implementing potent antiretroviral therapy
                          that is able to maximally suppress viral
                          replication. However, these drug combinations
                          do not result in viral eradication and, for
                          many patients, virologic and immunologic
                          control cannot be maintained. Even among
                          patients with apparent virologic control, a
                          ceiling effect seems to exist with failure
                          of CD4 cell counts to rise on average more
                          than 100 to 150 cells/mm3, at least during
                          the first 2 years of therapy. The incomplete
                          recovery of immune function after initiation
                          of therapy remains an obstacle in the
                          management of HIV. Preservation of immune
                          function by direct expansion of CD4
                          lymphocytes with IL-2 could represent a
                          significant additional treatment strategy. It
                          also has been speculated recently that IL-2
                          in combination with potent antiretroviral
                          therapy may be a useful approach for purging
                          HIV from the latently infected CD4 cells. It
                          is hoped that intervention with rIL-2 therapy
                          in combination with antiretroviral therapy at
                          an early stage of HIV infection can prevent
                          CD4 T-cell depletion and result in fewer
                          AIDS-defining illnesses than with
                          antiretroviral therapy alone.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive SC rIL-2 therapy or no SC rIL-2
                          therapy. All patients must receive
                          combination antiretroviral treatment, with
                          the choice of therapy at the discretion of
                          the treating clinician. However,
                          antiretroviral medications are not provided
                          by this study. Recombinant IL-2 is given SC
                          for 5 consecutive days every 8 weeks for at
                          least 3 cycles unless toxicities or other
                          contraindications develop. After the first
                          three cycles, additional cycles are given at
                          the discretion of each patient's physician,
                          with a general goal of maintaining the
                          patient's CD4 cell count at twice the
                          baseline level or at 1,000 cells/mm3 or above
                          for as long as possible. Patients in the no
                          SC rIL-2 group receive no injections.
                          Patients in both treatment groups are seen
                          every 4 months for follow-up data collection
                          to monitor viral load and CD4 cell counts.
                          All patients are followed for an average of 5
                          years. During the trial, patients in the no
                          SC rIL-2 group are not given rIL-2 at any
                          point. However, at the end of the study, if
                          rIL-2 is found to be effective in reducing
                          the rate of disease progression [AS PER
                          AMENDMENT 12/15/00: (new and recurrent
                          events)], including death, all patients are
                          offered rIL-2.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 4000 patients. 2000
                          patients in the SC rIL-2 group; 2000 patients
                          in the no SC rIL-2 group.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately 5
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1818/4000 010731.
PROTOCOL DETAILS          STUDY DURATION: Approximately 5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 91
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (001215)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: 00 I-0071
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection, documented by any
                          licensed ELISA test and confirmed by a second
                          method (e.g., Western blot) or any 1 of the
                          following at any time: detectable HIV p24
                          antigen, quantifiable plasma HIV RNA, or
                          detectable proviral DNA. 2. Absolute CD4 cell
                          count of 300 cells/mm3 or more within 45 days
                          prior to randomization. (For patients who are
                          status post-splenectomy, also a CD4 cell
                          percentage greater than 20 percent.).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 300 cells/mm3 For
                          patients who are status post-splenectomy,
                          also a CD4 cell percentage > 20%.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN Patients with
                          hyperbilirubinemia due to Gilbert's syndrome
                          or indinavir therapy may have a serum
                          bilirubin up to 5 x ULN (upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN or ALT <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Combination
                          antiretroviral therapy. Therapy can include
                          agents (approved and investigational)
                          administered through routine care or through
                          participation in clinical trials or expanded
                          access programs. The choice of combination
                          therapy is left to the discretion of the
                          treating clinician. Allowed with careful
                          monitoring: 1. Drugs with cardiotoxic effects
                          (e.g., doxorubicin). 2. Psychotropic drugs
                          (e.g., narcotics, analgesics, antiemetics,
                          sedatives, antidepressants, and
                          tranquilizers). 3. Beta-blockers and other
                          antihypertensives.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of an AIDS-defining illness (category
                          C, CDC,1993) or any of the following
                          conditions [AS PER AMENDMENT 12/15/00:
                          evidence of active clinical disease within
                          the past year for any AIDS-defining illness
                          (category C, CDC,1993) or any of the
                          following conditions]: extrapulmonary
                          Pneumocystis carinii disease;
                          multi-dermatomal herpes zoster (10 or more
                          lesions in a non-contiguous site); American
                          trypanosomiasis (Chagas' disease) of the
                          central nervous system (CNS); Penicillium
                          marneffii disease; visceral leishmaniasis;
                          non-Hodgkin's lymphoma of any cell-type;
                          Hodgkin's lymphoma; bartonellosis;
                          microsporidiosis (more than 1 month's
                          duration); nocardiosis; invasive
                          aspergillosis; or Rhodococcus equi disease.
                          2. History of autoimmune or inflammatory
                          diseases, including inflammatory bowel
                          disease (e.g., Crohn's disease or ulcerative
                          colitis), psoriasis, optic neuritis, or any
                          autoimmune/inflammatory diseases with
                          potentially life-threatening complications.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Recombinant
                          IL-2 therapy. 2. Systemic corticosteroids or
                          other immunosuppressants, or cytotoxic agents
                          within 45 days prior to randomization.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cytotoxic
                          agents. Hydroxyurea as part of the
                          antiretroviral regimen must be discontinued
                          14 days prior to each cycle of rIL-2. It may
                          be restarted 4 weeks after the cycle. 2.
                          Nephrotoxic medications (e.g.,
                          aminoglycosides and indomethacin) or
                          hepatotoxic medications (e.g., methotrexate
                          and asparaginase) due to possible
                          exacerbations of rIL-2-related kidney or
                          liver toxicities. 3. Glucocorticoids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy requiring cytotoxic chemotherapy.
                          2. Any CNS abnormality that requires ongoing
                          treatment with antiseizure medications. 3.
                          Autoimmune or inflammatory diseases,
                          including inflammatory bowel disease (e.g.,
                          Crohn's disease or ulcerative colitis),
                          psoriasis, optic neuritis, or any
                          autoimmune/inflammatory diseases with
                          potentially life-threatening complications.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: rIL-2 Group: Three
                          or more cycles of 7.5 MIU bid for 5
                          consecutive days, oncevery 8 weeks
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous injection
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 24 weeks (3 or
                          more 8-week cycles).
OTHER TREATMENT INFO.     END POINT: Disease progression, including
                          death. [AS PER AMENDMENT 12/15/00: New or
                          recurrent disease progression events,
                          including death.].
OTHER TREATMENT INFO.     DISCONTINUE: Patients who experience any of
                          the following events or conditions should
                          have their SC rIL-2 cycle delayed: 1.
                          Pregnancy or breast-feeding. 2. Intercurrent
                          illness that, in the judgment of the
                          clinician, would significantly affect
                          assessment of clinical status. 3. Use of
                          cytotoxic agents for any reason. 4. Toxicity
                          requiring temporary discontinuation. 5.
                          Inability to take combination antiretroviral
                          therapy during the 5-consecutive-day
                          treatment cycle. Patients who experience the
                          following events or conditions are
                          permanently discontinued from SC rIL-2: 1.
                          Toxicity requiring permanent discontinuation.
                          2. Patient or physician request to
                          discontinue.
OTHER TREATMENT INFO.     MODIFICATION: Patients should be monitored
                          closely for side effects of SC rIL-2.
                          Patients who experience dose-limiting side
                          effects may have their SC rIL-2 temporarily
                          interrupted or their dose reduced. All dose
                          reductions must be in 1.5 or 3.0 MIU/dose
                          decrements. The minimum dose of SC rIL-2 that
                          can be delivered under this protocol is 1.5
                          MIU bid. The maximum duration of each cycle
                          of dosing will be 5 consecutive days and will
                          not be extended for doses missed due to
                          management of toxicities.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                West Los Angeles VAMC 11301 Wilshire Boulvard
                          / 111-F Los Angeles, CA 90073 Barbara Rossman
                          [phone] Recruiting 000524.
DISTRICT OF COLUMBIA      Washington DC VA Medical Center 50 Irving
                          Street NW / 151B Washington, DC 20422 Barbara
                          Standridge [phone] Recruiting 000509.
FLORIDA                   Miami Veterans Administration Med Ctr 1201
                          Northwest 16th St Miami, FL 33125 Mack Smith
                          [phone] Recruiting 000707.
GEORGIA                   Atlanta VA Med Ctr 1670 Clairmont Rd Mailstop
                          RIM-111 Decatur, GA 30033 Susan Wirtz
                          [phone] Recruiting 001017.
ILLINOIS                  VA Chicago Health Care System - West Side Div
                          820 South Damen Ave Chicago, IL 60612 Mary Jo
                          Werhane [phone] Recruiting 000614.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd Chicago, IL 60657 Rita Verheggen
                          [phone] Recruiting 010404.
MARYLAND                  Natl Naval Med Ctr 8901 Wisconsin Ave
                          Bethesda, MD 208995000 Jean Vita
                          [phone] Recruiting 001130.
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 000310.
MINNESOTA                 Abbott-Northwestern Hosp / Clinic 42 2545
                          Chicago Ave South Minneapolis, MN 55404 Joann
                          Armstrong [phone] Recruiting 000509.
NEW JERSEY                Infectious Disease Specialists of NJ 1308
                          Morris Ave / Suite 204 Union, NJ 07083 Philip
                          Andrew [phone] Recruiting 001019.
OREGON                    The Research & Education Group 1650 NW Naito
                          Parkway Portland, OR 97209 Norma Martinez
                          [phone] Recruiting 010404.
OTHER                     Ospedale S Raffaele Via Stamira D Ancona / 20
                          Milano, Giuseppe Tambussi (390)226-437945
                          Recruiting 001024.
OTHER                     Hosp Ramon y Cajal Infectious Diseases
                          Service / Ctra Colmenar / Km 9.
OTHER                     Hosp Univ San Carlos C/Dr Martin Lagos s/n
                          Madrid, Maria Molina (349)133-03538
                          Recruiting 001012.
OTHER                     Hosp de la Princesa Internal Medicine and
                          Infectious Diseases Service / C/Diego de 62
                          Madrid, Ignacio Gil (349)152-02236 Recruiting
                          001012.
OTHER                     St Bartholomews Hosp Infection & Immunity
                          Clinical Group / Staff Grade Physician /
                          KGeorge V Block London, Des Maitland
                          (020)737-77457 Recruiting 001012.
OTHER                     Univ College London Med School Mortimer
                          Market Centre London, Diana Aldam
                          (020)738-09810 Recruiting 001012.
OTHER                     Saint Mary's Hosp Praed St / Paddington
                          London, Ken Legg (020)788-66790 Recruiting
                          001013.
OTHER                     Kennemer Gasthuis Lokatie EG Postbus 471 AK
                          Harlem, M Shoemaker (31 )23 -5522169
                          Recruiting 001204.
OTHER                     King's College Hosp Caldercot Centre / 15-22
                          Caldercot Road Cambewell, Dorrett Graham
                          (020)734-63479 Recruiting 001013.
OTHER                     Victoria Gen Hosp QE II Health Sciences Ctr
                          for Clinical Research / MacKenzie Bldg / Rm
                          124 West Annex 5790 University Ave Halifax,
                          Heather Haldane (902) 47-3 7431 Recruiting
                          001204.
OTHER                     General Infirmary at Leeds Dept of Sexual
                          Health Sunny Bank Wing / Great George Street
                          Leeds, Gerald Booth (011)339-26762 Recruiting
                          001013.
OTHER                     Gold Coast Sexual Health Clinic PO Box 44
                          Miami, John Chuah (61 )7 5-576 9033
                          Recruiting 001204.
OTHER                     North Manchester Gen Hosp Dept of Infectious
                          Diseases Research / Delauneys Rd Crumpsall
                          Manchester, Rob Daintith (016)172-02615
                          Recruiting 001013.
OTHER                     Universita degli Studi di Modena e Reggio
                          Emilia Clinica delle Malattie Infettive e
                          Tropicali / Via del Pozzo 71Modena , Giovanni
                          Guaraldi (39 )059- 422 799 Recruiting 001204.
OTHER                     Burwood Street General Practice 8 Burwood Rd
                          Burwood, Nicholas Doong (612)974-52755
                          Recruiting 001013.
OTHER                     St Elisabeth Zeikenhuis Hilvarenbeekseweg 60
                          Tilburg , M Sekkat (31 )13 -5391313
                          Recruiting 001204.
OTHER                     Stichting Medisch Centrum Jan van Goyen Jan
                          van Goyenkade 1 Amsterdam, Recruiting 001204.
OTHER                     Hopital Bichat - Claude Bernard 46 rue Henri
                          Huchard / Cedex 18 Paris, Sylvie Legac
                          (331)402-58080 Recruiting 001013.
OTHER                     Ruhr Univ Bochum Gudrunstr 56 Bochum,
                          Alexander Kreuter (923)4 5-093473 Recruiting
                          001130.
OTHER                     Holdsworth House General Practice Suite 1 32A
                          Holdsworth House Darlinghurst, Anthony Frater
                          (612)933-17228 Recruiting 000912.
OTHER                     Carlton Clinic 88 Rathdowne St Carlton,
                          Jonathan Anderson (613)934-79422 Recruiting
                          000913.
OTHER                     Marilyn McMurchie MD General Practice / 299
                          Oxford St First Floor Darlinghurst, Marilyn
                          McMurchie (612)933-17953 Recruiting 000913.
OTHER                     Hosp La Paz Consulta De Medicina / Interna li
                          - Consultas De Vih / Paseo DeCastellana 261
                          Madrid, Alicia Hernandez (349)172-77099
                          Recruiting 001012.
OTHER                     Hosp De Mostoles Consultas De Enfermedades
                          Infecciosas / C RioJucar S N MostoleMadrid,
                          Emilia Condes (349)166-48600 Recruiting
                          001012.
OTHER                     Prahran Market Clinic 131 Commercial Rd South
                          Yarra, Jeni Mitchell (613)982-64500
                          Recruiting 000913.
OTHER                     Royal Free Hosp Pond Street London, Deborah
                          Wilson (020)747-26232 Recruiting 001012.
OTHER                     Hosp Gen de Agudos Juan A Fernandez Cervino
                          3356 Buenos Aires, Carlos Zala
                          (541)148-082627 Recruiting 001017.
OTHER                     International Med Ctr of Japan 1-21-Toyama /
                          Shinjuku-ku Tokyo, Helen Fraser
                          (813)527-35418 Recruiting 000614.
OTHER                     Hosp Saint-Louis Service
                          d'iummuno-Hematologie I / Ave Claude Vellfaux
                          Paris Cedex IO, Laurence Gerard
                          (331)424-94731 Recruiting 001018.
OTHER                     Royal Sussex County Hosp Sussex House / 1
                          Abbey Road Brighton, Nicky Perry
                          (012)736-64532 Recruiting 001012.
OTHER                     Hvidovre Univ Hosp Kettegard Alle 30 /
                          DK-2650 Hvidore, Astrid Dilling-Hansen
                          [phone] Recruiting 000509.
OTHER                     Queensland Health - AIDS Med Unit PO Box 239
                          / Albert St Brisbane, Hugo Ree (617)322-45526
                          Recruiting 000913.
OTHER                     Centre Clinic 46 Acland St St Kilda, Nicholas
                          Medland (613)952-55866 Recruiting 000913.
OTHER                     Chonburi Reg Hosp Chonburi, Chureeratana
                          Bowaonwatanuwang [phone] Recruiting
                          001019.
OTHER                     Hosp Univ Germans Trias i Pujol Otra de
                          Canyet s/n 2 planta - Maternal / Badalona
                          Barcelona, Antoni Pastor (349)346-57897
                          Recruiting 000707.
OTHER                     Bourke Street Clinic 407 Bourke St Surry
                          Hills, Robyn Vale (612)933-22531 Recruiting
                          000913.
OTHER                     Chiangrai Reg Hosp 1039 Sathanpayaban Rd /
                          Muang District Chiangrai, Vithaya
                          Pongsurachet Recruiting 001019.
OTHER                     Univ of Tokyo Institute of Medical Science
                          Dept of Inf Dis & Appl Immun / 4-6-1
                          Shirokanedai Minoto-ku Tokyo, Tetsuya
                          Nakamura (813)544-95338 Recruiting 000707.
OTHER                     Ulleval Hosp Dept of Infectious Diseases
                          Oslo, Astrid Rudi [phone] Recruiting
                          000913.
OTHER                     Hosp Universitario Morales Meseguer Marques
                          de los Velez s/n Murcia, Rose Garrido
                          (349)683-60900 Recruiting 000913.
OTHER                     Odense Univ Hosp 5000 Odense C , Court
                          Pedersen (004)565-411816 Recruiting 000509.
OTHER                     Hosp Juan Ramon Jimenez Ronda Norte s/n
                          Huelva, Dolores Merino (349)592-01131
                          Recruiting 000913.
OTHER                     Marselisborg Hosp PP Orumsgrade Aarus C,
                          Niels Obel [phone] Recruiting 000509.
OTHER                     Hosp Carlos III Servicio De Infecciosos / C
                          Sinesio Delgado 10-12 Madrid, Luz Carbonero
                          (349)145-32500 Recruiting 001012.
OTHER                     Hosp Doce De Octubre Consultas De Vih / Ctra
                          De Andalucia Km 5 400 Madrid, Frederico
                          Pulido (349)139-08028 Recruiting 001012.
OTHER                     Klinikum Der Johann Wolfgang Goethe
                          Universitat Infektionsambulanz Haus 68 /
                          Zentrum Der Inneren Medizin TheodoStern Kai 7
                          Frankfurt, Claudia Wengenroth (496)963-017680
                          Recruiting 000524.
OTHER                     Venhalsan Soder Hosp SE-118 83 Stockholm,
                          Viveca Holmberg [phone] Recruiting
                          000524.
OTHER                     Albion Street Clinic Albion Street Centre /
                          150 Albion St Surry Hills, S Jeganathan
                          (612)933-21090 Recruiting 000922.
OTHER                     Klinik I fir Innere Medizin der Univ zu Koln
                          Studienburo fur Infektologie HIV / Haus 11 /
                          Joseph-Stelzmann-SKoln, Ellen Rund Recruiting
                          000922.
OTHER                     Chulalongkorn Univ Hosp HIV-NAT Research
                          Collaboration / 104 Rajdumri Rd Pathumwan,
                          Chris Ducombe (662)255-73345 Recruiting
                          000922.
OTHER                     Kaplan Med Ctr Ruth Ben Ari Institute of
                          Clinical Immunology and / AIDS CenterRehovot,
                          Annat Pilpoul (972)894-41486 Recruiting
                          001024.
OTHER                     Hosp Central de Asturias Hosp de Covadonga
                          6th Floor / Infectious Diseases - Internal
                          MeUnit Oviedo Asturias, Jose Maradona
                          Recruiting 001019.
OTHER                     Univ of Wuerzburg Josef-Schneider-Strasse 2
                          Bau 18 Wuerzburg, Thomas Vaeth
                          (499)312-013174 Recruiting 000719.
OTHER                     Rigohospitalet / Dept of Infectious Diseases
                          Rigshopitalet M 7701 / Blegdamsvej 9
                          Copenhagen, Lone Jensen [phone]
                          Recruiting 000509.
OTHER                     Haven Program Laurentian Hosp Sudbury
                          Regional Hosp Laurentian Site / 41 Ramsey
                          Lake Rd Sudburg, Judy Latendre-Paquette
                          [phone] Recruiting 000719.
OTHER                     Aalborg Hosp South Dept of Infectious
                          Diseases Aalborg, Carsten Larsen
                          [phone] Recruiting 000509.
OTHER                     Hosp Nuestra Sra De Aranzazu Infectious
                          Disease Unit / C/ Alto de Zorroaga s/n / San
                          SebastiGuipuzcoa, Francisco Arrondo
                          (349)430-07000 Recruiting 001024.
OTHER                     Hosp De Santa Maria Servicio De Doencas
                          Infecciosas / Av Prof Egaz Moniz Lisboa,
                          Francisco Antunes (351) 21- 793 8043
                          Recruiting 000817.
OTHER                     Osaka National Hosp AIDS Ctr / Clinical
                          Research Inst / 2-1-14 Houenzaka /
                          Chuou-kuOsaka-city Osaka, Sachiko Oda
                          (816)694-21331 Recruiting 001025.
OTHER                     Chelsea and Westminster Hosp St Stephens
                          Centre / 369 Fulham Road London, Ann Sullivan
                          (020)884-66132 Recruiting 001012.
OTHER                     The Research & Education Group 1650 NW Naito
                          Parkway Portland, OR 97209 Norma Martinez
                          (503)229
OTHER                     Gartnaval Gen Hosp The Brownlee Ctr / Great
                          Western Rd Glasgow, Sheila Evans
                          (014)121-11093 Recruiting 001006.
OTHER                     Western Gen Hosp Regional Infectious Diseases
                          Unit / Crewe Rd Edinburgh, Sheila Morris
                          (013)153-72842 Recruiting 001006.
OTHER                     Hosp del Mar Internal Medicine and Infectious
                          Diseases Unit / Paseo MaritimoBarcelona,
                          Alicia Gonzalez (349)322-11010 Recruiting
                          001031.
OTHER                     Royal Victoria Hosp Dept of Genitourinary
                          Medicine / Level 3B Outpatients Centre
                          Grosvenor Rd Belfast, Sinead McKernan
                          (028)908-94733 Recruiting 001006.
OTHER                     Hosp Juan Canalejo Internal Medicine / Ctra
                          de las Jubias 84 A Coruna, Javier Puig
                          (349)811-78189 Recruiting 001031.
OTHER                     Peterborough District Hosp Fenland Wing /
                          Thorpe Road Peterborough Cambridgeshire,
                          Adrian Palfreeman (017)338-74216 Recruiting
                          001013.
OTHER                     Centre Hosp de la Region Annecienne Service
                          des Maladie Infectieuses / L Ave de Tresum
                          ANNECY Cedex, Maryse Bensalem (334)508-83068
                          Recruiting 001101.
OTHER                     Univ of Alberta/Division of Inf Dis/Dept of
                          Med 24E13 Walter MacKenzie Edmonton , AB
                          Laura Mashinter (780) 40-7 1236 Recruiting
                          001130.
OTHER                     Toronto Gen Hosp 200 Elizabeth St / CWG 325
                          Toronto , ON Margaret McGrath-Chong
                          [phone] Recruiting 001012.
OTHER                     McMaster Univ Med Centre 1200 Main St West /
                          Rm 2F41 Hamilton, ON Sherie Savoy
                          [phone] Recruiting 000707.
OTHER                     Windsor Regional Hosp HIV Care Program / 1995
                          Lens Ave Windsor, ON Nancy McFarland
                          [phone] Recruiting 000707.
OTHER                     Univ de Sherbrooke / Ctr de Recherche
                          Clinique Ctr Univ de Sante de l'Estrie / 3001
                          12e Ave Nord Fleurimont, QC Mimose
                          Dambreville [phone] Recruiting 001012.
OTHER                     Montreal Chest Institute 3650 Saint Urbain St
                          Montreal , QC Sabrina Mastroprimiano
                          [phone] Recruiting 000824.
OTHER                     Centre Hospitalier Universitaire de Quebec
                          Pavillon CHUL / Rm S-745 / 2705 Boul Laurier
                          Ste-Foy, QC Lyne Lapointe [phone]
                          Recruiting 000824.
TEXAS                     Montrose Clinic 215 Westheimer Rd Houston, TX
                          77006 Brian Bell [phone] Recruiting
                          000509.
TEXAS                     Houston Veterans Administration Med Ctr 2002
                          Holcombe Blvd Houston, TX 77030 Katharine
                          Breaux [phone] Recruiting 000509.
TEXAS                     South Texas Veterans Health Care System 7400
                          Merton Minter Blvd San Antonio, TX 78284
                          Kimberly Summers [phone] Recruiting
                          000524.
TEXAS                     Univ TX Health Science Ctr 6431 Fannin St
                          Houston, TX 77030 Hilda Cuervo [phone]
                          Recruiting 000609.
WASHINGTON                Royal Perth Hosp Dept of Clinical Immunology
                          / GPO Box X2213 Perth , WA. Jenny Skett
                          (618)922-43429 Recruiting 000912.

90
UNIQUE IDENTIFIER         NIH/01237
PROTOCOL ID NUMBERS       CC 00 I-0020
PROTOCOL TITLE            Immunologic and Virologic Studies of
                          Intermittent versus Continuous Highly Active
                          Antiretroviral Therapy (HAART) in the
                          Treatment of HIV Disease.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To study the HIV-specific immune
                          responses, CD4 cell counts, plasma HIV RNA,
                          resistance to therapy, and toxicity and side
                          effects in HIV-infected individuals receiving
                          intermittent versus continuous antiretroviral
                          therapy.
GENERAL DESCRIPTION       RATIONALE: Although highly active
                          antiretroviral therapy (HAART) has been
                          successful in suppressing plasma HIV levels
                          in infected patients, virus replication
                          persists and viral levels have been shown to
                          rebound after withdrawing HAART. Long-term
                          use of HAART also carries risk of significant
                          toxicity and side effects. This study
                          examines the virologic and immunologic
                          effects of intermittent versus continuous
                          HAART in HIV-infected individuals with goals
                          of suppressing virus replication and
                          minimizing the toxicity and side effects of
                          HAART.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either continuous HAART or
                          intermittent HAART for 22 months.
                          Intermittent HAART consists of intervals of 1
                          month off therapy followed by 2 months on
                          therapy. The last on-therapy period lasts for
                          4 months. CD4 cell counts, viral loads,
                          incidence of toxicity and side effects,
                          HIV-specific immune responses, viral
                          resistance to therapy, and the viral
                          characteristics during rebound plasma viremia
                          are analyzed. Study visits are conducted once
                          a month for the first year and then once
                          every 3 months for patients in the continuous
                          HAART arm. Patients in the intermittent HAART
                          arm may have more frequent study visits
                          during the off-therapy periods. If viral load
                          increases significantly or CD4 cell count
                          decreases significantly, patients may have
                          their medications changed or, if they are
                          receiving intermittent therapy, may be
                          switched to continuous therapy.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Strategy determination.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 70 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/70.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection, documented by
                          positive ELISA and Western blot. 2. Absolute
                          CD4 cell count greater than or equal to 300
                          cells/mm3 within 30 days before
                          randomization. 3. History of viral levels
                          less than 500 copies/ml for the past 3
                          months, and levels less than 50 copies/ml
                          based on two determinations within 30 days
                          prior to enrollment (both measurements must
                          be below 50 to be eligible).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 300 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x ULN.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study Negative pregnancy test.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: At least 3 months
                          of ongoing HAART, defined as at least two
                          nucleoside reverse transcriptase inhibitors
                          in combination with either a nonnucleoside
                          reverse transcriptase inhibitor (excluding
                          nevirapine) or a protease inhibitor.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of chronic hepatitis B infection.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Substance abuse or
                          history of substance abuse that may interfere
                          with protocol compliance or compromise
                          safety.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Salvage HAART.
                          2. Experimental antiretrovirals less than 6
                          months prior to enrollment. 3. Interleukin-2
                          (IL-2).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: IL-2.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Evidence of resistance to licensed
                          antiretroviral medications as determined by
                          the principal investigator. 2. Significant
                          HIV-related illness, such as opportunistic
                          infections or malignancies other than
                          mucocutaneous Kaposi's sarcoma. 3.
                          Significant cardiac, pulmonary, kidney,
                          rheumatologic, gastrointestinal, hematologic,
                          or central nervous system (CNS) disease as
                          detectable on routine history, physical
                          examination, or screening laboratory studies.
                          4. Laboratory evidence of chronic hepatitis B
                          infection, including surface antigen
                          positivity. 5. Psychiatric illness.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Severe
                          toxicity. 2. Malignancy other than Kaposi's
                          sarcoma. 3. Life-threatening infection. 4.
                          Pregnancy. 5. Failure to comply with study
                          requirements. 6. Permanent discontinuation of
                          antiretroviral therapy.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 991201.

91
UNIQUE IDENTIFIER         NIH/01236
PROTOCOL ID NUMBERS       CC 92 I-0256
PROTOCOL TITLE            Evaluation of the Epidemiology, Clinical
                          Manifestations, Etiologies, and Immunology of
                          Human Immunodeficiency Virus (HIV) Negative
                          CD4 T Lymphocyte Deficient Patients.
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To better understand the
                          epidemiology, clinical manifestations,
                          causes, and immunologic abnormalities
                          associated with idiopathic CD4
                          T-lymphocytopenia. To provide blood cell
                          specimens for a repository for investigations
                          studying this syndrome.
GENERAL DESCRIPTION       RATIONALE: Cases of HIV seronegative persons
                          with low numbers of CD4+ T cells have been
                          reported in the medical literature to the
                          Centers for Disease Control (CDC) and at the
                          VIII International Conference on AIDS. Some
                          of these patients have had AIDS-defining
                          conditions like pneumocystis pneumonia. Very
                          little is currently known about the
                          epidemiology, clinical manifestations,
                          immunology, etiology, prognosis, and
                          appropriate management of these patients.
GENERAL DESCRIPTION       METHODOLOGY: Patients are assessed initially
                          and then once yearly in order to better
                          understand the epidemiology, clinical
                          manifestations, causes, and immunologic
                          abnormalities associated with idiopathic CD4
                          T-lymphocytopenia. Treatment is not provided
                          but diagnostic studies may be performed if
                          needed to investigate a possible diagnosis.
                          All patients have a history and physical
                          examination and blood drawn for standard
                          laboratory tests, an immunologic evaluation,
                          and an assessment for retroviruses. Patients
                          are also asked to complete a questionnaire.
                          This evaluation generally provides no benefit
                          to the patient; however, patients who choose
                          to be seen are contributing to a better
                          understanding of this entity.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Questionnaire, Natural history.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Patients will
                          be followed for as long a period of time as
                          the principal investigator deems useful,
                          which may vary between a single visit and
                          multiple visits over 5 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/100.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Seronegativity.
PROTOCOL DETAILS          STUDY DESIGN: Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seronegativity confirmed by
                          ELISA. 2. Adeqate health care outside of NIH.
                          3. CD4 count less than 300 cells/mm3 on 2
                          consecutive samples.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 300 cells/mm3 on two
                          consecutive samples.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Chemotherapeutic agents. 2. Corticosteroids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Disease
                          such as intestinal lymphangiectasia that
                          might, in the opinion of the principal
                          investigator, provide a reasonable
                          alternative explanation for the CD4
                          lymphopenia or confound the evaluation.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 991122.

92
UNIQUE IDENTIFIER         NIH/01235
PROTOCOL ID NUMBERS       NIAID ACTG A5055
PROTOCOL TITLE            A Phase I/II, Randomized, Open-Label Study of
                          the Safety and Pharmacokinetics of Indinavir
                          + Ritonavir Therapy in HIV-Infected Subjects
                          Failing Amprenavir, Nelfinavir, Saquinavir,
                          or Nelfinavir/Saquinavir Combination Therapy.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: Two regimens containing different
                          dosages of indinavir (IDV) and ritonavir
                          (RTV) are compared in patients failing
                          amprenavir (APV), nelfinavir (NFV),
                          saquinavir (SQV), or NFV/SQV combination. The
                          primary objectives are to assess the clinical
                          tolerability and laboratory toxicity and to
                          compare the pharmacokinetic characteristics
                          of the two IDV plus RTV regimens.
GENERAL DESCRIPTION       RATIONALE: IDV, a protease inhibitor, has
                          shown excellent clinical and virologic
                          responses when combined with 2 nucleoside
                          analogues. Although effective, the
                          pharmacokinetics of IDV make it difficult to
                          use in many patients. The drug has a short
                          half-life and requires administration in high
                          doses every 8 hours with significant dietary
                          restrictions. Research has shown that IDV
                          kinetics can be improved significantly by the
                          addition of RTV, allowing for administration
                          of IDV at lower doses every 12 hours. The
                          half-life of IDV is prolonged 3- to 5-fold
                          when administered with RTV. Based on these
                          results, it is reasonable to study this
                          combination as a twice-daily dosing regimen.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive 1 of 2 doses of IDV/RTV for 24 weeks
                          (Arms A and B). All patients also receive 2
                          nucleoside reverse transcriptase inhibitors
                          (NRTIs). The NRTIs are not provided by the
                          study. Clinical assessments take place at
                          Weeks 1, 2, 4, 8, 12, 16, 20, and 24 which
                          includes a virology assessment. [AS PER
                          AMENDMENT 4/21/00: Patients who experience a
                          confirmed virologic failure (defined in
                          protocol) and elect to remain on study
                          treatment, are followed through Week 24.
                          Patients who experience a confirmed virologic
                          failure and elect to discontinue study
                          treatment will have a final evaluation at the
                          time of treatment discontinuation.] Patients
                          are hospitalized for 12 hours at the Week 2
                          study visit for an intensive pharmacokinetic
                          analysis.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy, Drug
                          safety, Drug tolerance, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 50 patients. [AS PER
                          AMENDMENT 4/21/00: Approximately 50
                          patients.].
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 35/50 010712.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 30
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (000421)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5055
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Dose-Response Design
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. (Patients
                          without adequate source documentation but
                          with strong clinical evidence of HIV
                          infection may have the HIV ELISA and
                          confirmatory test performed at the screening
                          evaluation and results confirmed prior to
                          study entry.) 2. Plasma HIV-1 RNA PCR value
                          between 500 and 100,000 copies/ml by any
                          laboratory (ACTG or non-ACTG) certified in
                          and using the Roche standard Amplicor HIV-1
                          Monitor or UltraSensitive RT PCR assay within
                          45 days prior to study entry. 3. Ability and
                          willingness to maintain a vigorous hydration
                          with 1.5 L of water or other fluids daily.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 10.0 g/dl for men; > 9.5 g/dl
                          for women within 45 days of study entry.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 Within 45 days
                          of study entry.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN Within 45 days of
                          study entry. ULN (Upper Limit of Normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN Within 45 days of
                          study entry.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.5 x ULN Within 45 days of
                          study entry.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN Within 45 days of
                          study entry.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80 Within 45 days of study
                          entry.
PATIENT INCLUSION CRIT.   OTHER: Genotype assay as specified in
                          protocol. Within 45 days of study entry:
                          Urine protein < 2+. Normal lipase or
                          pancreatic amylase value. [AS PER AMENDMENT
                          4/21/00: Fasting triglyceride level < 750
                          mg/dl.].
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Negative
                          pregnancy test within 14 days of study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: 1. Treatment with
                          APV, NFV, SQV, or NFV/SQV combination therapy
                          plus two NRTIs for at least 12 weeks prior to
                          study entry. [AS PER AMENDMENT 4/21/00: This
                          must be the first PI-containing regimen.
                          Patients must be taking this regimen at
                          screening.] 2. Naive to at least one NRTI,
                          defined as 14 days or less consecutive days
                          of prior NRTI use, except for 3TC, for which
                          any exposure is defined as experienced.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required:
                          Chemoprophylaxis for Pneumocystis carinii
                          pneumonia for all patients with CD4 counts of
                          200 cells/mm3 or less. Allowed: 1. Topical
                          and oral antifungal agents, except for
                          fluconazole at a dose of 400 mg or higher, or
                          oral ketoconazole or itraconazole. 2.
                          Treatment, maintenance, or chemoprophylaxis
                          for OIs as clinically indicated (see
                          Exclusion Concurrent Medications for
                          exceptions). 3. All antibiotics as clinically
                          indicated. 4. Systemic corticosteroid use for
                          21 days or less for acute problems as
                          medically indicated. Chronic systemic
                          corticosteroid use is not permitted, unless
                          it is within physiological replacement
                          levels. 5. Recombinant erythropoietin (rEPO)
                          and granulocyte colony-stimulating factor
                          (G-CSF, filgrastim) as medically indicated.
                          6. Regularly prescribed medications such as
                          antipyretics, analgesics, allergy
                          medications, antidepressants, sleep
                          medications, oral contraceptives, megestrol
                          acetate, testosterone, or any other
                          medications as medically indicated, unless
                          excluded in Exclusion Concurrent Medications.
                          (Because of the possibility that RTV may
                          alter the effectiveness of oral
                          contraceptives or medroxyprogesterone, these
                          must not be used as the sole form of birth
                          control.) 7. Alternative therapies such as
                          vitamins, acupuncture, and visualization
                          techniques. [AS PER AMENDMENT 4/21/00: Note:
                          Refer to package insert for potential drug
                          interactions with IDV or RTV that may require
                          dose adjustment of concomitant medications.]
                          Allowed after Week 4 study visit with
                          approval of chair or co-chair: Appropriate
                          FDA-approved NRTIs, such as didanosine,
                          lamivudine, stavudine, zalcitabine,
                          zidovudine, and/or abacavir, may replace an
                          NRTI that is discontinued due to toxicity.
                          Concomitant use of either stavudine and
                          zidovudine or zalcitabine and lamivudine is
                          not permitted.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Active opportunistic infection (OI) or other
                          opportunistic disease requiring medication in
                          the 14 days prior to study entry. 2. Any
                          active infection requiring acute treatment
                          within 14 days of study entry. 3. History of
                          any illness that, in the opinion of the
                          investigator, might confound the results of
                          the study or pose additional risk in
                          administering study drugs to the patient. 4.
                          A new onset of unexplained temperature above
                          38.5 C for any 7 consecutive days in the 30
                          days prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any PI other
                          than APV, NFV, SQV, or NFV/SQV combination.
                          2. Nonnucleoside reverse transcriptase
                          inhibitors (NNRTIs) within 30 days prior to
                          study entry. 3. Cytochrome P450 enzyme
                          inducers or cytochrome P450 inhibitors within
                          14 days of study entry. (Note: Use of
                          fluconazole at a dose less than 400 mg is
                          allowed if all other criteria are met.) 4.
                          Any systemic immunomodulator or
                          investigational therapy within 30 days of
                          study entry. 5. Active immunization within 21
                          days of study entry. [6. AS PER AMENDMENT
                          4/21/00: Lipid-lowering agents including
                          drugs known as statins within 30 days of
                          study entry.] [7. AS PER AMENDMENT 4/21/00:
                          St. John's wort within 30 days of study
                          entry.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. All
                          antiretroviral therapies other than study
                          medications [AS PER AMENDMENT 4/21/00: and 2
                          NRTIs]. 2. All investigational drugs. 3.
                          Systemic cytotoxic chemotherapy. 4.
                          Cytochrome P450 substrates, as specified in
                          the protocol. 5. Fluconazole at a dose of 400
                          mg or higher, or oral ketoconazole or
                          itraconazole. 6. Chronic systemic
                          corticosteroid use is not permitted, unless
                          it is within physiological replacement
                          levels. 7. Concomitant use of stavudine and
                          zidovudine or zalcitabine and lamivudine. [8.
                          AS PER AMENDMENT 4/21/00: Lipid-lowering
                          agents including drugs known as statins.] [9.
                          AS PER AMENDMENT 4/21/00: St. John's wort.]
                          Avoided: Herbal medications [AS PER AMENDMENT
                          4/21/00: unless excluded above].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Medical condition that would preclude
                          successful completion of the study. 2.
                          Malignancy, including Kaposi's sarcoma, that
                          requires systemic chemotherapy. 3. Genotypic
                          assay at screening that indicates 3 or more
                          mutations in HIV-1 protease at codons 10, 36,
                          46, 54, 71, 82, 84, and/or 90. Specifically,
                          these include L10I,R,V; M36I; M46I/L; I54V;
                          A71V; V82A,T,F; I84V; and/or L90M.
                          Demonstration of wild type is acceptable.
                          (Patients with plasma HIV-1 RNA confirmed
                          greater than or equal to 500 but less than or
                          equal to 1,000 copies/ml at screening are
                          excluded from genotypic analysis and are
                          eligible if they meet all other criteria. If
                          RNA PCR amplification cannot be obtained on
                          patients with plasma HIV-1 RNA greater than
                          1,000 but less than or equal to 5,000
                          copies/ml, these patients are still eligible
                          if they meet all other criteria.).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0233  Indinavir sulfate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Arm A: 200 mg q12h.
                          Arm B: 400 mg q12h. (Note: To improve
                          tolerability in Arm B, RTV is administered
                          atmg q12h during the initial 4 days of study
                          treatment and then increased to 400 mg q12h
                          starting on Day 5.) Drug 2: Arm A: 800 mg
                          q12h. Arm B: 400 mg q12h
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Arm A: 400 mg. Arm B:
                          800 mg. Drug 2: Arm A: 1,600 mg. Arm B: 800
                          mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Assessment of clinical
                          tolerability and laboratory toxicity of the
                          two regimens. Evaluation of the
                          pharmacokinetic characteristics of IDV with
                          the 2 IDV-plus-RTV regimens.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Noncompliance.
                          2. Requirement for treatment with systemic
                          therapy to treat a malignancy or with
                          disallowed study medications. 3. Patient or
                          physician requests. 4. Clinical reasons that
                          the investigator believes are
                          life-threatening. 5. Pregnancy or
                          breast-feeding. 6. Disease progression. 7. An
                          NRTI is switched or stopped and the patient
                          is unable to take an NRTI to which the
                          patient is naive, or all NRTIs are
                          permanently discontinued. 8. Study
                          medication-related toxicities.
OTHER TREATMENT INFO.     MODIFICATION: Patients who develop Grade 3
                          toxicities in the IDV/RTV (400/400 mg) arm of
                          the study that, in the opinion of the
                          protocol chair, are secondary to RTV may be
                          switched to the IDV/RTV (800/200 mg) arm.
                          Patients who develop Grade 3 toxicities in
                          the IDV/RTV (800/200 mg) arm that, in the
                          opinion of the chair, are secondary to IDV
                          may be switched to the IDV/RTV (400/400 mg)
                          arm. No other dose modifications or
                          reductions are allowed for IDV or RTV. Dose
                          interruptions or discontinuations are made
                          for all Grade 3 or higher toxicities or per
                          protocol.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 000403.
CALIFORNIA                Marin County Specialty Clinic 161 Mitchell
                          Building Suite 200 San Rafael, CA 94903 Marc
                          Gould [phone] Recruiting 000310.
CALIFORNIA                Univ of California / San Diego Treatment Ctr
                          2760 5th Ave / Suite 300 San Diego, CA
                          921036325 Jill Kunkel [phone] No longer
                          recruiting 000721.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 010717.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          000310.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 001031.
COLORADO                  Denver Dept of Health and Hosps 4200 East 9th
                          Ave / Campus Box B-196 Denver, CO 80262 M
                          Graham Ray [phone] Recruiting 000614.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000310.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone] No
                          longer recruiting 000621.
ILLINOIS                  Cook County Hosp 637 South Wood Chicago, IL
                          60612 Edward Goodwin [phone] No longer
                          recruiting 001005.
INDIANA                   Methodist Hosp of Indiana / Life Care Clinic
                          1633 North Capital Ave Indianapolis, IN 46202
                          Sarah Ryan [phone] Recruiting 000112.
INDIANA                   Division of Inf Diseases/ Indiana Univ Hosp
                          1001 West 10th St / OPW 430 Indianapolis, IN
                          46202 Beth Zwickl [phone] Recruiting
                          000112.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 000112.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Rebecca Becker
                          [phone] Recruiting 010723.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / PO Box
                          437 Minneapolis, MN 55455 Christine Fietzer
                          [phone] Recruiting 000203.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Barbara
                          Longmire [phone] Recruiting 000112.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 000112.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 001012.
NEW YORK                  Chelsea Ctr Cornell Univ Clinical Trials Unit
                          / 525 East 68th St New York, NY 10021 Brenda
                          Greenhill [phone] Recruiting 000524.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 000817.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 000112.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Brenda Greenhill [phone]
                          Recruiting 000419.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 000515.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 000515.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] Recruiting
                          000509.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 001110.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 001012.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone] No
                          longer recruiting 001121.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 001110.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] No longer recruiting
                          010430.

93
UNIQUE IDENTIFIER         NIH/01233
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-06-001
PROTOCOL TITLE            Procedure for Initiation, Administration, and
                          Discontinuation of Interleukin-2 (IL-2)
                          Therapy in Conjunction with Highly Active
                          Antiretroviral Therapy.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To augment and prolong HIV-specific
                          cytotoxic lymphocyte (CTL) response. To
                          reduce the extent of damage and accelerate
                          immune system recovery. To delay and reduce
                          recurrent viremia compared to historical
                          controls.
GENERAL DESCRIPTION       RATIONALE: At the time of initial HIV
                          infection, CD4 cells are susceptible to
                          infection, and the virus infects many T cells
                          during the first 4 to 6 weeks. Many of these
                          infected cells subsequently maintain the
                          virus in a latent state. Immune
                          reconstitution with daily low-dose IL-2
                          therapy is intended to correct or improve the
                          deficiency in CD4 cells, while maintaining a
                          high frequency of CD8+ HIV-specific CTL and
                          increasing natural killer (NK) cells. After a
                          year of HAART plus IL-2, it may be possible
                          to discontinue HAART while maintaining IL-2
                          stimulatory therapy, and the immune
                          reactivity repaired and stimulated by IL-2
                          should be able to contain the virus and
                          maintain latency.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to add
                          IL-2 to their current HAART regimen or simply
                          to remain on their current HAART regimen.
                          IL-2 therapy is initiated at Month 3 of
                          HAART. IL-2 is injected subcutaneously daily
                          for 9 months, in addition to HAART. After
                          completion of this 1-year treatment period,
                          patients are evaluated for discontinuation of
                          HAART. Patients with a viral load below 50
                          copies/ml throughout HAART plus IL-2, a CD4
                          count of at least 500 cells/mm3, and no onset
                          of opportunistic infections may have HAART
                          discontinued and IL-2 continued as
                          monotherapy for an additional 6 months. After
                          completing 6 months of IL-2 monotherapy,
                          eligible patients may have IL-2 therapy
                          discontinued.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Immunotherapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: OPEN patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 72/OPEN 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Plasma HIV level by Roche RT-PCR
                          assay of 5,000 copies/ml or less on 2
                          consecutive assays within 3 months; the last
                          2 before starting IL-2 therapy and 1 log10 or
                          greater decline from baseline. 2. Completion
                          of at least 3 months of treatment with HAART.
                          3. A refrigerator for storage of IL-2
                          syringes.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Completion of at
                          least 3 months of treatment with HAART.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Glucocorticoids or other immunosuppressive
                          agents. 2. Immunomodulating agents, e.g.,
                          interferon-alpha, granulocyte
                          colony-stimulating factor (G-CSF), or
                          granulocyte-macrophage colony-stimulating
                          factor (GM-CSF).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 1.2 mIU/M2 body
                          surface area (BSA); may be escalated bymIU/M2
                          BSA
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 1.2 mIU/M2 body surface
                          area (BSA); may be escalated bymIU/M2 BSA
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous
                          injections
OTHER TREATMENT INFO.     MODIFICATION: If dose-limiting toxicity
                          (e.g., weakness, fatigue, lethargy, myalgias,
                          and low-grade fever) occurs, then therapy
                          with IL-2 is withheld until signs and
                          symptoms resolve. IL-2 is reinitiated at
                          resolution of signs and symptoms at a lower
                          dosage.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
MARYLAND                  Johns Hopkins Hosp 600 North Wolfe St
                          Baltimore, MD 21205 Beulah Perdue
                          [phone] Recruiting 010723.

94
UNIQUE IDENTIFIER         FDA/01231
PROTOCOL ID NUMBERS       FDA B007
PROTOCOL TITLE            A Bridging Dose-Escalation Study of the
                          Safety, Pharmacokinetic Properties, and
                          Immunologic Effect of Subcutaneous L2-7001
                          (Recombinant Human Interleukin-2) in Patients
                          Infected with HIV with CD4+ T-Cell Counts of
                          300 to 500 Cells/mm3 and Viral Burden Under
                          10,000 Copies/ml on Active Antiretroviral
                          Therapy (ART).
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: The primary objective of the first
                          phase of the trial is to evaluate the safety
                          and tolerability of a modified form of
                          recombinant human interleukin-2, L2-7001, and
                          to estimate a maximum tolerated dose (MTD) in
                          patients infected with HIV. The primary
                          objective of the second phase of the trial is
                          to assess the immunologic efficacy of three
                          different doses of intermittent subcutaneous
                          (SC) L2-7001 in combination with ART on CD4+
                          T cell count as compared with ART alone.
                          Methodology: This study takes place in two
                          phases. Phase A consists of an open-label
                          dose-escalation of L2-7001 through four dose
                          levels. Ascending dose cohorts of five
                          patients are studied. The safety and
                          tolerability of L2-7001 is assessed in
                          preparation for the second phase of the study
                          and to estimate an MTD. Phase B involves
                          randomization of 190 patients to (a) one of
                          three dose levels of L2-7001 plus ART, (b)
                          one of two dosing levels of Proleukin plus
                          ART, or (c) ART alone. L2-7001 and Proleukin
                          are given SC every 12 hours for the first 5
                          days of an 8-week cycle for three cycles.
                          Serum IL-2 levels, soluble IL-2 receptor
                          levels, and levels of pro-inflammatory
                          cytokines are evaluated in 8 patients
                          randomized to each treatment cohort of Phase
                          B. All patients completing this phase of the
                          protocol are eligible to be screened for
                          enrollment in a maintenance use protocol
                          which will allow for access to L2-7001.
GENERAL DESCRIPTION       METHODOLOGY: This study takes place in two
                          phases. Phase A consists of an open-label
                          dose-escalation of L2-7001 through four dose
                          levels. Ascending dose cohorts of five
                          patients are studied. The safety and
                          tolerability of L2-7001 is assessed in
                          preparation for the second phase of the study
                          and to estimate an MTD. Phase B involves
                          randomization of 190 patients to (a) one of
                          three dose levels of L2-7001 plus ART, (b)
                          one of two dosing levels of Proleukin plus
                          ART, or (c) ART alone. L2-7001 and Proleukin
                          are given SC every 12 hours for the first 5
                          days of an 8-week cycle for three cycles.
                          Serum IL-2 levels, soluble IL-2 receptor
                          levels, and levels of pro-inflammatory
                          cytokines are evaluated in 8 patients
                          randomized to each treatment cohort of Phase
                          B. All patients completing this phase of the
                          protocol are eligible to be screened for
                          enrollment in a maintenance use protocol
                          which will allow for access to L2-7001.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010718)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Maximum tolerated dose (MTD).
PROTOCOL DETAILS          PROJECTED ACCRUAL: 212 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately 3
                          months for Phase A and 6 months for Phase B.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 29/212 000712.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 23
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: CS-MM-9901
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Dose-Response Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have the following symptoms and conditions:
                          1. HIV infection, documented by a positive
                          ELISA test and Western blot or by detectable
                          plasma viral load measurement (greater than
                          500 RNA copies/ml using an ultrasensitive
                          bDNA or PCR test or greater than 1,500 RNA
                          copies/ml using a non-ultrasensitive bDNA or
                          PCR test). 2. A viral load below 10,000
                          copies/ml at 2 time points within 2 months of
                          study entry. 3. A CD4+ T cell count mean of 2
                          points, obtained within 2 months of study
                          entry, between 300 and 500 cells/mm3. 4.
                          Women with childbearing potential should have
                          a negative pregnancy test within 28 days
                          prior to study entry and practice effective
                          contraception throughout the study, including
                          at least one form of barrier protection.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 300 to 500 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN Patients with Gilbert's
                          syndrome or indinavir-induced
                          hyperbilirubinemia must have a serum
                          bilirubin no greater than 5 times ULN.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 4.9 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 4.9 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 g/dl.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable ART for 4
                          months. ART must consist of two or more
                          agents, at least one of which must be a
                          protease inhibitor or a nonnucleoside agent.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: ART.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of autoimmune disease.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Recreational drug or
                          alcohol use that, in the opinion of the
                          principal investigator, would affect patient
                          safety and/or compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. IL-2 therapy.
                          2. Hydroxyurea within 4 months of study
                          entry. 3. Systemic corticosteroids or any
                          agent, licensed or experimental, with known
                          immunomodulatory effects within 4 weeks of
                          study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Other
                          cytokines (with the exception of
                          erythropoietin), systemic corticosteroids,
                          hydroxyurea, immunomodulatory therapy,
                          cytotoxic agents, or antimetabolites.
                          (Exceptions may be made for brief periods of
                          steroid administration for serious or
                          life-threatening medical events, such as
                          Pneumocystis carinii pneumonia [PCP].)
                          Allowed with extreme caution: Iodinated
                          contrast dye. Patients receiving IL-2 who are
                          exposed to iodinated contrast dye may
                          experience an acute onset of adverse
                          reactions.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active AIDS-defining clinical illness (CDC
                          Category C, 1993 definition). If a patient
                          has a history of an AIDS-defining condition
                          that has been cured or in a state of
                          remission for at least 1 year, he or she is
                          not excluded on the basis of this history. 2.
                          Clinically significant cardiac, pulmonary, or
                          neurologic impairment, hemostasis disorder,
                          or other medical condition that would, in the
                          opinion of the principal investigator, affect
                          patient safety and/or compliance. 3.
                          Psychiatric or cognitive disturbance or
                          illness that, in the opinion of the principal
                          investigator, would affect patient safety
                          and/or compliance. 4. Concurrent malignancy
                          requiring systemic chemotherapy. 5.
                          Uncontrolled diabetes or hypothyroidism.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: q 12 hours for 5
                          days every 8 weeks
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous injection
OTHER TREATMENT INFO.     MODIFICATION: Proleukin and L2-7001
                          dose-adjustments for toxicity will be allowed
                          in a codified manner as set forth in the
                          protocol.
SUPPORTING AGENCY         Chiron Corp.
LAST REVISION DATE        20010718
ALABAMA                   Sorra Research Ctr / Med Forum 950 N 22nd St
                          / Suite 550 Birmingham, AL 35203 Bonnie
                          Brewer [phone] Recruiting 000819.
CALIFORNIA                St Lukes Medical Group 1855 First Ave San
                          Diego, CA 92101 Rebecca Gonzalez
                          [phone] Recruiting 000818.
CALIFORNIA                Pacific Oaks Research 8641 Wilshire Blvd
                          Beverly Hills, CA 90211 Brenda Perry
                          [phone] Recruiting 000818.
CALIFORNIA                Kaiser Foundation Hospital 4141 Geary Blvd /
                          Suite 219 San Francisco, CA 94118 Mary Beth
                          Charland [phone] Recruiting 000818.
CALIFORNIA                Orange County Ctr for Special Immunology
                          11190 Warner Ave / Suite 411 Fountain Valley,
                          CA 92708 Tonya Rhoads [phone]
                          Recruiting 000818.
COLORADO                  Denver Inf Disease Consultants 4545 E 9th Ave
                          / Suite 120 Denver, CO 80220 Cheryl Stewart
                          [phone] Recruiting 000818.
DISTRICT OF COLUMBIA      Dupont Circle Physicians Group 1737 20th St
                          NW Washington, DC 200091104 Linda Green
                          [phone] Recruiting 000818.
FLORIDA                   Steinhart Medical Associates 3659 South Miami
                          Ave / Suite 4006 Miami, FL 33133 Amy S
                          Liebmann [phone] Recruiting 991026.
FLORIDA                   Specialty Med Care Ctrs of South Florida Inc
                          1313 NW 36th St Miami, FL 33142 Maria Paredes
                          [phone] Recruiting 000818.
FLORIDA                   Community AIDS Resource Inc 1320 South Dixie
                          Hwy Coral Gables, FL 33146 Christiane Jones
                          [phone] Recruiting 000818.
ILLINOIS                  Northstar Med Clinic 2835 North Sheffield Ave
                          Chicago, IL 60657 Matt Sirinek [phone]
                          Recruiting 000818.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd #108 Chicago, IL 60657 Rita
                          Verheggen [phone] Recruiting 000814.
MASSACHUSETTS             Fenway Community Health Ctr 7 Haviland St
                          Boston, MA 02115 Lorraine Schieve
                          [phone] Recruiting 000818.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Candy Tobin [phone]
                          Recruiting 000818.
NEW YORK                  Anderson Clinical Research Inc 97-45 Queens
                          Blvd / 12th Floor Rego Park, NY 11374 Yolanda
                          Sipin [phone] Recruiting 000818.
NEW YORK                  Albany Med College 47 New Scotland Ave / MC
                          142 Albany, NY 12208 Sandra Preston
                          [phone] Recruiting 000818.
OKLAHOMA                  Associates in Med and Mental Health 2325 S
                          Harvard / Suite 600 Tulsa, OK 74114 Jennifer
                          Dunn [phone] Recruiting 000818.
OREGON                    Research and Education Group 2701 NW Vaughn
                          St Portland, OR 97210 Norma Martinez
                          [phone] Recruiting 000818.
PENNSYLVANIA              Anderson Clinical Research 225 Penn Ave
                          Pittsburgh, PA 15221 John Meneski
                          [phone] Recruiting 000818.
TEXAS                     N Texas Ctr for AIDS & Clin Rsch 3514 Cedar
                          Springs Rd / Suite 200 Dallas, TX 75219 Kathy
                          Hanks [phone] Recruiting 000818.
TEXAS                     Central Texas Clinical Research 1015 East
                          32nd Street / Suite 215 Austin, TX 78705
                          Peggy Wright [phone] Recruiting 000818.
TEXAS                     Joseph Gathe Private Practice 1200 Binz St /
                          Suite 120 Houston, TX 77004 Jennifer Welch
                          [phone] Recruiting 000818.
WASHINGTON                Virginia Mason Med Ctr 1100 9th Ave Seattle,
                          WA 98101 Cheryl Weaver [phone]
                          Recruiting 000814.

95
UNIQUE IDENTIFIER         NIH/01228
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-05-003
PROTOCOL TITLE            A Phase II, Randomized, Open-Label Study of
                          Maximally Assisted Therapy (MAT) Compared to
                          Self-Administered Therapy (SAT) for the
                          Treatment of HIV Infection in Antiretroviral
                          Naive Subjects with CD4 Greater Than or Equal
                          to 200 Cells/mm3.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To compare the rate and durability
                          of virologic suppression in patients
                          receiving maximally assisted therapy (MAT)
                          versus self-administered therapy (SAT) at 24
                          weeks, and then at 48 weeks and 72 weeks of
                          follow-up.
GENERAL DESCRIPTION       RATIONALE: Novel approaches are needed to
                          improve adherence to combination
                          antiretroviral therapy. Nonadherence can lead
                          to reduced drug levels and inadequate viral
                          suppression, which accelerates drug
                          resistance. Thus nonadherence in the first
                          few months of primary HIV infection can limit
                          therapeutic options for an individual years
                          later. Barriers to optimal treatment
                          adherence in patients with early HIV
                          infection include complex treatment regimens
                          which disrupt daily routines, drug
                          intolerance, and concomitant illness
                          including depression. Directly observed
                          therapy has been successful in improving
                          overall effectiveness of antituberculosis
                          therapy and may be a useful strategy in
                          HIV-infected patients.
GENERAL DESCRIPTION       METHODOLOGY: All patients receive combination
                          antiretroviral therapy with didanosine (ddI),
                          stavudine (d4T), efavirenz (EFV), and
                          nelfinavir (NFV). Patients are randomized to
                          self-administered (SAT) versus observed (MAT)
                          therapy for 24 weeks. Patients randomized to
                          MAT receive one directly observed dose (ddI,
                          d4T, EFV, and NFV) of their antiretroviral
                          regimen by a field worker or nurse at the
                          clinic 5 days per week. As a reminder for the
                          second NFV and d4T dose, MAT patients are
                          provided with an alarm watch programmed to
                          sound at dosing times. The alarm watch also
                          serves as a reminder for weekend doses that
                          will not be directly observed. Patients
                          randomized to SAT receive standard care. All
                          patients are monitored with monthly plasma
                          HIV RNA levels and CD4 and CD8 cell counts.
                          At Week 24, all patients are crossed over to
                          SAT for an additional 48 weeks of follow-up.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Adherence.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 74 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 72 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 74/74 000824.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (981214)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AEHIV 003: MAT
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Cross-Over Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. History of HIV infection documented
                          by a positive HIV antibody test by a licensed
                          EIA and confirmed by Western blot, IFA, or
                          HIV RNA. 2. CD4 count of at least 200
                          cells/mm3 within 30 days prior to study
                          entry.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 200 cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN or ALT (SGPT) <= 5 x
                          ULN (Upper Limit of Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 3 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80 %.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry Abstinence or effective method of
                          birth control / contraception including oral
                          contraceptives during the study.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Proven or suspected acute hepatitis within 30
                          days prior to study entry, even if AST (SGOT)
                          and ALT (SGPT) are 5 times the upper limit of
                          normal or less. 2. A history of Grade 2 or
                          higher bilateral peripheral neuropathy within
                          60 days prior to study entry. 3. A history of
                          pancreatitis.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current alcohol
                          abuse, at the discretion of the local
                          investigator.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Any
                          antiretroviral agents.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Investigational drugs and vaccines. 2.
                          Rifabutin or rifampin. 3. Oral ketoconazole,
                          terfenadine, astemizole, cisapride,
                          triazolam, or midazolam. 4. Interferon,
                          interleukins, GM-CSF, or HIV vaccines. 5. All
                          antiretroviral therapies other than study
                          medications. 6. Systemic cytotoxic
                          chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: A
                          malignancy which requires systemic therapy
                          other than minimal Kaposi's sarcoma.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0269  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0263  Nelfinavir mesylate
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 400 mg qd. (250 mg
                          qd for patients weighing less than 6Drug 2:
                          40 mg bid. Drug 3: 600 mg qd. Drug 4: 1250 mg
                          bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 400 mg. (250 mg for
                          patients weighing less than 60 kg.)Drug 2: 80
                          mg. Drug 3: 600 mg. Drug 4: 2500 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 72 weeks.
OTHER TREATMENT INFO.     END POINT: To compare the percentage of
                          subjects with undetectable HIV RNA at 24 and
                          72 weeks and to evaluate the maximum
                          reduction in HIV RNA at 24 and 72 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: Grade 3 or higher
                          toxicity (with exceptions).
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
CALIFORNIA                UCSD 2760 5th Ave / Suite 300 San Diego, CA
                          92103 Joanne Santangelo [phone]
                          Recruiting 991115.
TEXAS                     Univ of Texas Southwestern Med Ctr 5323 Harry
                          Hines Blvd Dallas, TX 75235 Phillip Keiser
                          [phone] Recruiting 991115.

96
UNIQUE IDENTIFIER         NIH/01227
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-05-001
PROTOCOL TITLE            An Observational Study of Subjects with
                          Primary HIV Infection: A Study of the UCSD
                          Acute/Early HIV Infection (AEHIV) Clinical
                          Studies Unit.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To characterize the dynamics of
                          viral populations and host immune response in
                          blood, lymph nodes, cerebrospinal fluid
                          (CSF), and vaginal secretions or semen in
                          patients with acute and early HIV-1
                          infection.
GENERAL DESCRIPTION       RATIONALE: Primary HIV-1 infection is
                          frequently identified as a nonspecific viral
                          syndrome occurring within 20 days to 8 weeks
                          following a documented HIV exposure. However,
                          symptoms vary from person to person, and some
                          people undergo asymptomatic seroconversion.
                          Because of the difficulty identifying
                          patients with either acute HIV infection
                          (within 30 days of initial infection) or
                          early infection (within 12 months of initial
                          infection), no systematic review of viral
                          dynamics or immunodynamics in this patient
                          population has been undertaken. A better
                          understanding of the virologic and
                          immunologic parameters during acute and early
                          HIV infection should provide information
                          relevant to the optimal design of future
                          clinical therapeutic trials.
GENERAL DESCRIPTION       METHODOLOGY: The only patient intervention is
                          obtaining blood, lymph node tissue, CSF, and
                          semen or vaginal secretion specimens at
                          designated intervals according to the
                          schedule of evaluations. Patients are
                          followed for 5 years. Patients may elect to
                          start or discontinue antiretroviral therapy
                          at any time; however, no antiretroviral
                          therapy is administered as part of this
                          study. Descriptive analysis includes
                          tolerance and toxicity, magnitude and
                          durability of RNA suppression, magnitude and
                          durability of immunologic responses (CD4 and
                          CD8 cells), and decay and emergence of
                          resistant virus in tissue reservoirs (CSF,
                          genital secretions, and lymph nodes).
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Clinical Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 5 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 81/100 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: 4 (980414)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: SD AEHIV 001. AEHIV
                          001
PROTOCOL DETAILS          STUDY DESIGN: Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Evidence of acute (within 30 days of
                          initial infection) or early (within 12 months
                          of initial infection) HIV infection. Acute
                          HIV infection is defined as a negative ELISA
                          test and a positive HIV RNA PCR or HIV p24
                          antigen in the setting of a negative Western
                          blot. Early HIV infection, in an individual
                          with a documented negative HIV ELISA at some
                          point during the previous 12 months, is
                          defined as a positive ELISA test confirmed by
                          either a positive or evolving Western blot,
                          positive HIV RNA PCR, or detection of HIV
                          antigen.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
CALIFORNIA                UCSD 2760 5th Ave / Suite 300 San Diego, CA
                          92103 Susan Little [phone] Recruiting
                          991019.

97
UNIQUE IDENTIFIER         NIH/01226
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-05-005
PROTOCOL TITLE            Outcomes of Antiretroviral Therapy During
                          Primary HIV Infection.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To evaluate the effect of potent
                          antiretroviral therapy, initiated before or
                          after HIV seroconversion, on the development
                          and decay rate of the reservoir of latently
                          infected cells and on the development and
                          maintenance of the HIV-specific cellular
                          immune response. To compare the viral burden
                          in transmitting source partners of newly
                          HIV-infected patients and non-transmitting
                          HIV-infected partners of persons with
                          suspected primary HIV infection.
GENERAL DESCRIPTION       RATIONALE: Although many researchers have
                          recommended initiation of aggressive
                          antiretroviral therapy as soon as possible
                          after HIV infection occurs, the tolerability
                          and efficacy of this approach has not been
                          systemically evaluated. Many features of
                          primary HIV pathogenesis are incompletely
                          understood. A more complete understanding of
                          immune dynamics and viral pathogenesis during
                          primary HIV infection is critical to
                          determine optimal treatment intervention
                          strategies. This study will evaluate the
                          outcomes of potent antiretroviral therapy
                          initiated at different stages of primary HIV
                          infection.
GENERAL DESCRIPTION       METHODOLOGY: Thirty-six of the study patients
                          are coenrolled to ACTG 371 or another
                          treatment protocol. All study drug treatment
                          and toxicity management is performed
                          according to guidelines in these treatment
                          protocols. An untreated cohort of 12 patients
                          is also followed on this study. Patients are
                          stratified at enrollment according to their
                          stage of acute or early HIV infection.
                          Patients are evaluated for virologic,
                          immunologic, and clinical parameters for 96
                          weeks. In addition, novel studies of source
                          partner identification are proposed. An
                          effort is made to determine the most likely
                          source partner(s) for each study patient on
                          the basis of patient recall of possible
                          exposures. A separate study protocol will
                          evaluate the source partner.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 48 patients. 16 patients
                          per site.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 96 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 13/48 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (990310)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AEHIV 005
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Evidence of acute or recent HIV
                          infection. Acute HIV infection is defined as
                          detectable viral activity with a positive
                          plasma HIV RNA of at least 2,000 copies/ml
                          within 7 days prior to study entry, performed
                          by any Roche certified laboratory (ACTG or
                          non-ACTG), and one of the following: (1)
                          negative ELISA; (2) positive ELISA but
                          negative or indeterminate Western blot (# 2
                          bands); or (3) positive ELISA and Western
                          blot but with documented negative ELISA or
                          plasma HIV RNA in the preceding 30 days.
                          Recent HIV seroconversion is defined as a
                          positive ELISA and Western blot with a
                          negative ELISA or plasma HIV RNA in the
                          preceding 30 to 90 days.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
CALIFORNIA                UCSD 2760 5th Ave / Suite 300 San Diego, CA
                          92103 Joanne Santangelo [phone]
                          Recruiting 991115.
CALIFORNIA                Cedars Sinai Med Ctr 8700 Beverly Blvd /
                          B-217 / AIDS and Immune Disorders Center Los
                          Angeles, CA 90048 Dr Eric Darr [phone]
                          Recruiting 991115.
CALIFORNIA                San Francisco Gen Hosp / UCSF AIDS Program
                          995 Potrero Ave / Building 80 / Ward 84 San
                          Francisco, CA 94110 Dr. Jim Kahn
                          [phone] Recruiting 991115.

98
UNIQUE IDENTIFIER         NIH/01225
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-05-007
PROTOCOL TITLE            The Determinants of the Biology of HIV
                          Transmission to Determine the Immunologic and
                          Virologic Characteristics of Those Who May
                          Have Transmitted HIV to Another Individual.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To assess the viral characteristics
                          (including resistance patterns and viral
                          heterogeneity) in blood, genital fluid (semen
                          or cervical-vaginal washings), and saliva
                          among the partners of those with suspected
                          primary HIV infection. To determine the level
                          of CD8 non-cellular activity and CD8 cellular
                          antiviral factor (CAF) in blood and genital
                          fluid among the partners of those with
                          suspected primary HIV infection.
GENERAL DESCRIPTION       RATIONALE: Persons with early HIV infection
                          may represent high transmission risk to their
                          partners. Early infection, characterized by
                          rapid virologic replication, insufficient
                          immunologic control of infection, and more
                          rapid course of disease progression, may be
                          associated with increased infectiousness. The
                          viral determinants of transmission may in
                          part be explained by viral burden in blood,
                          genital fluids, and oral cavity fluids. All
                          three fluids may be the source for
                          transmitted virus.
GENERAL DESCRIPTION       METHODOLOGY: Persons with suspected HIV
                          infection are asked to identify their
                          possible source partners. The importance of
                          partner referral is emphasized and assisted
                          recruitment or active tracing is offered if
                          necessary. Source partners will not be
                          approached uninvited. If a partner states
                          that he/she does not want to be contacted,
                          then he/she will not be contacted further for
                          the purpose of this study or for any other
                          study. All patients are offered HIV
                          counseling and plasma testing for HIV-1 RNA
                          and CD4+ cells. Blood specimens are collected
                          for plasma determination, and cellular and
                          plasma fractions are collected for CAF and
                          neutralization antibodies. Neutralization
                          assays are used to detect humoral immune
                          response in patients with primary HIV
                          infection. Genital fluids and saliva are
                          analyzed for viral RNA. Patients are seen in
                          the clinic on Day 1 for blood draw and return
                          2 weeks later for blood test results. A
                          follow-up period of at least 4 weeks is
                          planned. Compensation is provided to all
                          patients.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Natural history.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients. 48 source
                          partners who are HIV-infected and transmit
                          the virus to their partner plus 48 source
                          partners who are HIV-infected and do not tr
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 4
                          weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 4/20 010731.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (980707)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: UCSD Project 98-0776.
                          AEHIV 007
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Been the sexual partner or injection
                          drug use partner of a person with suspected
                          recent HIV infection and acute retroviral
                          syndrome, or have documentation of acute HIV
                          seroconversion. 2. Ability to provide written
                          consent. 3. Availability for a follow-up
                          period of at least 4 weeks.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
CALIFORNIA                UCSD 2760 5th Ave / Suite 300 San Diego, CA
                          92103 Joanne Santangelo [phone]
                          Recruiting 991115.
CALIFORNIA                Cedars Sinai Med Ctr 8700 Beverly Blvd /
                          B-217 / AIDS and Immune Disorders Center Los
                          Angeles, CA 90048 Dr Eric Darr [phone]
                          Recruiting 991115.
CALIFORNIA                San Francisco Gen Hosp / UCSF AIDS Program
                          995 Potrero Ave / Building 80 / Ward 84 San
                          Francisco, CA 94110 Dr. Jim Kahn
                          [phone] Recruiting 991115.

99
UNIQUE IDENTIFIER         NIH/01221
PROTOCOL ID NUMBERS       NIAID CPCRA 062
PROTOCOL TITLE            Adherence Strategies Using a Medication
                          Manager and an Electronic Medication Reminder
                          System for HIV-Infected Patients Receiving
                          HAART.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To evaluate the effects of two
                          adherence interventions, a medication manager
                          and an electronic medication reminder system,
                          on the durability of suppression of HIV RNA
                          level among antiretroviral (AR)-naive
                          patients enrolling in the FIRST (Flexible
                          Initial Retrovirus Suppressive Therapies)
                          study (CPCRA 058) and AR-experienced patients
                          enrolling in the PIP (Protease Inhibitor
                          Progression) study (CPCRA 057).
GENERAL DESCRIPTION       RATIONALE: Adherence to AR therapy has become
                          increasingly important in the management of
                          HIV infection. Adherence to AR regimens is
                          thought to be a critical factor in
                          maintaining therapeutic drug levels, thus
                          helping ensure viral suppression and
                          minimizing the risk of drug resistance.
                          However, AR regimens are often complex with
                          demanding dosing schedules. Patients often
                          miss doses because they simply forget; other
                          factors such as substance abuse, depression,
                          and low literacy levels also contribute to
                          nonadherence. Adherence is influenced not
                          only by individual behavior but also by the
                          services, the quality of the patient-provider
                          relationship, and the amount of social
                          support offered the patient. There is no
                          currently agreed upon, widely used, and
                          generalizable intervention for improving
                          adherence over the long course of HIV
                          therapy. This study provides a long-term
                          comparative evaluation of two interventions.
GENERAL DESCRIPTION       METHODOLOGY: Clinical sites, rather than
                          individual patients, are randomized to one of
                          four groups: a medication manager, an
                          electronic medication reminder system, a
                          medication manager plus an electronic
                          medication reminder system, or usual care.
                          Special training sessions are held for the
                          staff of participating units assigned to
                          medication manager and/or electronic
                          medication reminder system interventions. The
                          medication manager is a research staff member
                          who works individually with study patients,
                          addressing the knowledge, motivation, and
                          skills necessary for adherence. The
                          electronic medication reminder system is ALR
                          (A Little Reminder). This is a small,
                          portable alarm that is programmed to sound
                          and flash at the times of the patient's
                          scheduled AR medication doses. Patients
                          enrolling into either the FIRST or PIP study
                          at clinical sites authorized to carry out
                          this study are offered the option of
                          participating in the adherence intervention
                          to which the clinical site has been randomly
                          assigned. Data collected through the FIRST
                          and the PIP protocols are used to address the
                          Adherence study objectives. Patients on the
                          FIRST protocol are assessed for time to first
                          virologic failure (confirmed rise in viral
                          load above 2,000 copies/ml). Also, patients
                          on the FIRST and PIP studies are assessed for
                          changes in viral load, resistance, CD4 cell
                          counts, adherence, and other factors.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Clinical Evaluation, Adherence.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 592 patients. 592 patients
                          from the FIRST protocol (CPCRA 058) and 400
                          patients from the PIP protocol (CPCRA 057).
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: A patient's
                          participation in the Adherence study will
                          continue throughout follow-up in the FIRST or
                          PIP study.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 838/592 010731.
PROTOCOL DETAILS          STUDY DURATION: 5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (990909)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Random
                          Allocation; Factorial Design Study;
                          Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Enrolled into either the FIRST (CPCRA
                          058) or the PIP (CPCRA 057) study after the
                          patient's clinical site has been authorized
                          to begin this Adherence study.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients are excluded for the
                          following reasons: 1. Enrollment at a
                          clinical site that routinely uses a
                          medication manager or an electronic
                          medication reminder system in a standardized
                          manner. 2. Enrollment at a clinical site that
                          is unable to participate.
OTHER TREATMENT INFO.     END POINT: For patients enrolling in the
                          FIRST study: time to first virologic failure.
                          For patients enrolling in the PIP study or
                          the FIRST study: other measures of plasma HIV
                          RNA level change, AR drug resistance, CD4
                          counts, reported AR adherence, changes in AR
                          regimen, Grade 4 adverse events, and quality
                          of life.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Community Consortium / UCSF 3180 18th St /
                          Suite 201 San Francisco, CA 94110 Carroll
                          Child [phone] Recruiting 991019.
COLORADO                  Denver CPCRA / Denver Public Hlth 605 Bannock
                          St Denver, CO 802044507 Jack Rouff
                          [phone] Recruiting 991019.
CONNECTICUT               Yale Univ School of Medicine / AIDS Program
                          135 College St / Suite 323 New Haven, CT
                          06510 Laurie Andrews [phone] No longer
                          recruiting 010612.
DISTRICT OF COLUMBIA      Washington Reg AIDS Prog / Dept of Infect Dis
                          VA Med Ctr / 50 Irving St NW Washington, DC
                          20422 Barbara Standridge [phone]
                          Recruiting 991019.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon Ave / Suite 130 Atlanta, GA 303081962
                          Melanie Thompson MD [phone] No longer
                          recruiting 010528.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd #108 Chicago, IL 60657 Rita
                          Verheggen [phone] Recruiting 991019.
LOUISIANA                 Louisiana Comm AIDS Rsch Prog / Tulane Univ
                          Med 1430 Tulane Ave / TB 21 New Orleans, LA
                          70112 Janice Walker [phone] Recruiting
                          991019.
MICHIGAN                  Henry Ford Hosp 2799 West Grand Blvd /
                          CFP-104 Detroit, MI 48202 Diane Mastro-Polak
                          [phone] Recruiting 991019.
MICHIGAN                  Wayne State Univ - WSU/DMC / Univ Hlth Ctr
                          4201 Saint Antoine / POD 7C Detroit, MI 48201
                          Jan Kosmyna [phone] Recruiting 991019.
NEW JERSEY                Southern New Jersey AIDS Clinical Trials Dept
                          of Medicine / 3 Cooper Plaza / Suite 513
                          Camden, NJ 08103 Carol Graeber [phone]
                          Recruiting 991019.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Robert C Sawyer [phone]
                          Recruiting 991019.
NEW MEXICO                Partners in Research / New Mexico 915 Camino
                          de Salud NE Albuquerque, NM 87131 Cynthia
                          Nicholson [phone] Recruiting 991019.
NEW YORK                  Bronx-Lebanon Hosp Ctr Vaccine Trial Site /
                          1645 Grand Concourse Suite 1G Bronx, NY 10453
                          Elizabeth Doramajian [phone] Recruiting
                          010119.
NEW YORK                  Harlem AIDS Treatment Grp / Harlem Hosp Ctr
                          506 Lenox Ave / Rm 3101A New York, NY 10037
                          Luis Fuentes [phone] Recruiting 991019.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn St Portland, OR 97210 Norma Martinez
                          [phone] Recruiting 991019.
PENNSYLVANIA              Philadelphia FIGHT 1233 Locust St / 5th Floor
                          Philadelphia, PA 19107 Jane Shull
                          [phone] Recruiting 991019.
TEXAS                     Univ TX Health Science Ctr 6431 Fannin St
                          Houston, TX 77030 Hilda Cuervo [phone]
                          Recruiting 001114.
VIRGINIA                  Richmond AIDS Consortium / Div of Infect
                          Diseases PO Box 980049 Richmond, VA 232980049
                          Vinnie Mitchell [phone] Recruiting
                          991019.

100
UNIQUE IDENTIFIER         NIH/01220
PROTOCOL ID NUMBERS       NIAID ACTG A5061
PROTOCOL TITLE            A Phase II, Restrictively Randomized,
                          Open-Label, Pilot Study of Treatment
                          Intensification of Early Virologic Failure.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To determine whether adding 1 or 2
                          drugs to the current initial antiretroviral
                          regimen is an effective strategy for treating
                          the first viral rebound in patients who are
                          able to complete 24 weeks of therapy with an
                          intensified regimen. [AS PER AMENDMENT
                          11/9/00: To investigate whether adding 1 or 2
                          drugs to the current, initial (background)
                          antiretroviral therapy (ART) is a potential
                          effective strategy capable of suppressing and
                          maintaining plasma HIV-1 RNA below 500
                          copies/ml up to Week 24 in patients
                          experiencing first viral rebound.] [AS PER
                          AMENDMENT 04/03/01: To investigate whether
                          adding 1 or 2 drugs to the current, potent,
                          background antiretroviral therapy (ART)
                          regimen is a potential effective strategy
                          capable of suppressing and maintaining plasma
                          HIV-1 RNA below 500 copies/ml up to Week 24
                          in patients experiencing virologic rebound.]
GENERAL DESCRIPTION       RATIONALE: Successful therapy following viral
                          rebound has been problematic. Intensification
                          of the existing regimen by adding 1 or 2
                          drugs generally has been avoided. However,
                          successfully adding new drugs to an existing
                          regimen would be advantageous since it would
                          expose the patient to fewer antiretroviral
                          agents in the overall treatment course.
                          Recent evidence suggests that a significant
                          proportion of patients who experience viral
                          rebound while receiving a protease inhibitor
                          (PI) actually have viral rebound with a
                          PI-sensitive virus. Other studies have shown
                          that treatment decisions based on resistance
                          assays result in better virologic outcomes.
                          This trial examines further the effect of
                          resistance assay-directed intensification of
                          a PI-containing antiretroviral regimen on
                          viral load. [AS PER AMENDMENT 04/03/01: The
                          antiretroviral regimen need not contain a
                          protease inhibitor.]
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified by
                          baseline plasma HIV-1 RNA levels (5,000
                          copies/ml or less versus greater than 5,000
                          copies/ml). Patients undergo phenotypic drug
                          resistance testing prior to study entry.
                          Based on the phenotypic results, patients are
                          [AS PER AMENDMENT 11/9/00: selectively]
                          randomized equally to 1 of 3 [AS PER
                          AMENDMENT 11/9/00: 1 of 2] intensification
                          strategies while remaining on their current,
                          initial [AS PER AMENDMENT 11/9/00:
                          (background)] antiretroviral therapy (ART).
                          [AS PER AMENDMENT 04/03/01: ART need not be
                          initial.] A patient is excluded from
                          randomization to an arm if that arm contains
                          a drug to which the patient has phenotypic
                          resistance. Arm A adds abacavir (ABC). Arm B
                          adds amprenavir (APV) [AS PER AMENDMENT
                          11/9/00: and ritonavir (RTV)]. Arm C adds
                          didanosine (ddI) plus hydroxyurea (HU). [AS
                          PER AMENDMENT 11/9/00: Arm C has been
                          discontinued.] A patient's HIV must be
                          sensitive to at least 3 drugs. [AS PER
                          AMENDMENT 11/9/00: Each patient must be
                          taking at least 3 drugs to which his/her HIV
                          isolate is sensitive, including ABC or APV
                          and at least 2 other drugs that are part of
                          the current, initial (background) ART. If
                          phenotypic resistance testing at screening
                          indicates resistance to a nucleoside reverse
                          transcriptase inhibitor (NRTI) drug in the
                          patient's current, initial (background) ART,
                          then the local investigator may choose to
                          discontinue that drug. However, the patient
                          and local investigator may choose to continue
                          the drug but it will not be considered an
                          active drug per this protocol.] [AS PER
                          AMENDMENT 04/03/01: ART need not be initial.]
                          Patients have regular clinic visits for
                          physical exams and blood tests, including CD4
                          and CD8 cell counts, plasma HIV-1 RNA assays,
                          and tests for pharmacokinetic variability. In
                          the event of viral rebound of 500 copies/ml
                          or more at Week 12 or later,
                          phenotypic/genotypic drug resistance is
                          assayed. In addition, phenotypic drug
                          resistance is assayed at the primary endpoint
                          (Week 24) and at the end of treatment (Week
                          48) on all patients.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 42 patients. [AS PER
                          AMENDMENT 11/9/00: 10-21 patients for Arm A
                          and 10-21 patients for Arm B. Arm C has been
                          discontinued and is closed to accrual.].
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/42.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 9
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (010403)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG A5061
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection, as documented by
                          any licensed ELISA test kit and confirmed by
                          either Western blot, HIV-1 culture, HIV-1
                          antigen, plasma HIV-1 RNA, or a second
                          antibody test by a method other than ELISA at
                          any time prior to study entry. 2. Prior
                          plasma HIV-1 RNA PCR or bDNA value below 500
                          copies/ml on 2 consecutive occasions [AS PER
                          AMENDMENT 11/9/00: at least 24 hours apart]
                          while receiving the initial ART regimen [AS
                          PER AMENDMENT 04/03/01: ART need not be
                          initial], by an accepted method as outlined
                          in the study protocol. 3. Current viral
                          rebound, defined as plasma HIV-1 RNA levels
                          between 500 and 10,000 copies/ml, confirmed
                          within 30 days and maintained for no more
                          than 16 weeks prior to screening. [AS PER
                          AMENDMENT 11/9/00: Current viral rebound,
                          defined as plasma HIV-1 RNA levels between
                          500 and 10,000 copies/ml within 16 weeks
                          prior to the first study screening. The
                          plasma HIV-1 RNA sample obtained at study
                          screening can serve as the confirmatory test
                          and must be performed within 16 weeks of the
                          initial rebound. Any HIV-1 RNA determinations
                          obtained between the time of initial rebound
                          and the first study screening must be between
                          500 and 10,000 copies/ml.][AS PER AMENDMENT
                          04/03/01: Viral rebound, defined as plasma
                          HIV-1 RNA levels between 500 and 10,000
                          copies/ml.] Viral rebound must have occurred
                          following the 2 consecutive plasma HIV-1 RNA
                          levels below 500 copies/ml. 4. CD4 cell count
                          of 100 cells/mm3 or more at both the most
                          recent CD4 evaluation while on the initial
                          ART [AS PER AMENDMENT 04/03/01: ART need not
                          be initial], prior to [AS PER AMENDMENT
                          11/9/00: the first] screening (by any
                          laboratory) and at [AS PER AMENDMENT 11/9/00:
                          the first] screening (by an ACTG-certified
                          laboratory). [AS PER AMENDMENT 11/9/00: The 2
                          CD4 counts must be separated by at least 24
                          hours.] 5. An evaluable phenotypic resistance
                          assay result from ViroLogic, Inc. at study
                          entry indicating the virus is sensitive to 3
                          or more drugs. One of these drugs must be
                          ABC, APV, or ddI. [AS PER AMENDMENT 11/9/00:
                          At least 1 of these drugs must be ABC or
                          APV/RTV. The drug ddI has been discontinued
                          from this study.] At least 2 other drugs must
                          be part of the patient's current, initial ART
                          regimen. [AS PER AMENDMENT 04/03/01: ART need
                          not be initial.] [AS PER AMENDMENT 11/9/00:
                          Study-provided RTV in Arm B is not considered
                          an active drug. RTV dosed at 400 mg or more
                          bid as part of the background ART is
                          considered an active drug.] 6. Signed,
                          informed consent by a parent or legal
                          guardian for patients under age 18. Note:
                          Patients may be allowed co-enrollment in
                          other studies if approved by the protocol
                          chair or vice chairs.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10.0 g/dl for men, >= 9.5 g/dl
                          for women [AS PER AMENDMENT 11/9/00].
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 60 days after Negative
                          pregnancy test Oral contraceptives may not be
                          used alone but may be used with barrier
                          contraception.
PATIENT INCLUSION CRIT.   OTHER: Allowed: Prisoners, as determined by
                          local IRBs.
PATIENT INCLUSION CRIT.   PRIOR TREATMENT: Allowed: Acupuncture and
                          visualization techniques.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Current, initial,
                          potent, PI-containing ART regimen [AS PER
                          AMENDMENT 04/03/01: ART need not be initial
                          and need not contain a PI.] of at least 3
                          drugs taken for at least 24 weeks.
                          (Substitution of agents in the initial ART
                          regimen [AS PER AMENDMENT 04/03/01: ART need
                          not be initial] could have been made if the
                          substitution was due to intolerance to some
                          agent and not due to virologic or clinical
                          failure. Patients must be on their current
                          initial ART regimen [AS PER AMENDMENT
                          04/03/01: ART need not be initial] for at
                          least 28 days prior to screening.).
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii
                          pneumonia (recommended for all patients with
                          a CD4 cell count of 200 cells/mm3 or less).
                          2. Topical and oral antifungal agents, except
                          for oral ketoconazole and itraconazole. [AS
                          PER AMENDMENT 11/9/00: Topical and oral
                          antifungal agents.] 3. Treatment,
                          maintenance, or chemoprophylaxis with
                          approved agents for opportunistic infections
                          unless specifically prohibited elsewhere in
                          this protocol. 4. Rifabutin at a reduced dose
                          of 150 mg/day [AS PER AMENDMENT 11/9/00: for
                          patients randomized to Arm B (APV/RTV).
                          Patients randomized to Arm A (ABC) may
                          receive rifabutin at full dose (300 mg/day).]
                          5. Antibiotics as clinically indicated unless
                          specifically prohibited elsewhere in this
                          protocol. 6. Systemic corticosteroid use for
                          21 days or less for acute problems as
                          medically indicated. 7. Recombinant
                          erythropoietin (rEPO) and granulocyte
                          colony-stimulating factor (G-CSF, filgrastim)
                          as medically indicated. 8. Regularly
                          prescribed medications such as antipyretics,
                          analgesics, allergy medications,
                          antidepressants, sleep medications, oral
                          contraceptives, megestrol acetate,
                          testosterone, or any other medications not
                          specifically prohibited elsewhere in this
                          protocol, as medically indicated. (Due to
                          potential interactions between study
                          medications and oral contraceptives or
                          medroxyprogesterone, these cannot be used as
                          the only form of birth control.) 9.
                          Alternative therapies such as vitamins [AS
                          PER AMENDMENT 11/9/00: (unless specifically
                          prohibited elsewhere in this protocol)].
                          Allowed with caution with APV: Dapsone,
                          erythromycin, carbamazepine, phenobarbital,
                          phenytoin, itraconazole, alprazolam,
                          clorazepate, diazepam, flurazepam, diltiazem,
                          nicardipine, nifedipine, nimodipine,
                          atorvastatin, cerivastatin, lovastatin,
                          pravastatin, simvastatin, delavirdine,
                          efavirenz, nevirapine, estrogens,
                          progestogens, glucocorticoids, clozapine,
                          loratadine, pimozide, cimetidine, ritonavir,
                          sildenafil, antacids, didanosine, amiodarone,
                          systemic lidocaine, tricyclic ant
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of any illness that, in the opinion
                          of the investigator, might confound study
                          results or pose additional risk in
                          administering study drugs to the patient. 2.
                          Unexplained temperature above 38.5 C during
                          the 7 consecutive days prior to [AS PER
                          AMENDMENT 11/9/00: the first] study
                          screening. Patients with the following prior
                          condition are excluded from Arm A: History of
                          hypersensitivity to abacavir. Patients with
                          the following prior condition are excluded
                          from Arm C: History of pancreatitis. [AS PER
                          AMENDMENT 11/9/00: Arm C has been
                          discontinued.].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Active
                          immunization within 21 days prior to [AS PER
                          AMENDMENT 11/9/00: the first] study
                          screening. 2. Acute therapy for a serious
                          infection or other serious medical illnesses
                          that are potentially life-threatening and
                          require systemic therapy and/or
                          hospitalization within 7 days prior to study
                          entry. [3. AS PER AMENDMENT 11/9/00:
                          Saquinavir (SQV)-Invirase as the sole PI at
                          the first screening evaluation and refusal to
                          change to SQV-Fortovase.] Excluded from Arm
                          A: ABC at [AS PER AMENDMENT 11/9/00: the
                          first] screening or ABC for more than 4 weeks
                          prior to study entry. Excluded from Arm B:
                          APV at [AS PER AMENDMENT 11/9/00: the first]
                          screening or APV for more than 4 weeks prior
                          to study entry. Excluded from Arm C: HU or
                          ddI or ZDV at screening or either HU or ddI
                          for more than 4 weeks prior to study entry.
                          [AS PER AMENDMENT 11/9/00: Arm C has been
                          discontinued.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          immunomodulatory agents except HU. [AS PER
                          AMENDMENT 11/9/00: Any investigational
                          immunomodulatory agents.] 2. Investigational
                          drugs without specific approval from the
                          protocol chairs. 3. Acute therapy for any
                          infection or medical illness (e.g.,
                          vaginitis, folliculitis, bronchitis,
                          pharyngitis), with the exception of oral
                          thrush. 4. Systemic cytotoxic chemotherapy.
                          5. All ARTs other than medications comprising
                          the intensified regimen and study
                          medications. 6. Oral ketoconazole and
                          itraconazole (other topical and oral
                          antifungal agents are permitted). [AS PER
                          AMENDMENT 11/9/00: All topical and oral
                          antifungal agents are permitted.] 7. Chronic
                          systemic corticosteroid use (more than 21
                          days), unless such use is within
                          physiological replacement levels. The study
                          chair must be contacted in these instances.
                          8. Herbal medications. [9. AS PER AMENDMENT
                          11/9/00: Hypericum perforatum (St. John's
                          wort).] [AS PER AMENDMENT 11/9/00: Excluded
                          with APV and RTV]
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Simultaneous
                          intolerance to ABC, APV, and ddI or
                          simultaneous intolerance to ABC, APV, and HU.
                          [AS PER AMENDMENT 11/9/00: Intolerance to ABC
                          for Arm A and intolerance to APV for Arm B.
                          The drugs ddI and HU have been discontinued
                          from this study.] 2. Phenotypic resistance to
                          the PI that is part of the current initial
                          ART regimen. 3. Malignancy, including
                          Kaposi's sarcoma, that requires systemic
                          chemotherapy. [AS PER AMENDMENT11/9/00:
                          Excluded from Arm A: Phenotypic resistance to
                          ABC. Excluded from Arm B: Phenotypic
                          resistance to APV.].
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0258  Amprenavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: [AS PER AMENDMENT
                          11/9/00: Arm B: 100 mg bid, except noif the
                          background regimen contains RTV. If the
                          background regicontains EFV, dose is 200 mg
                          bid.] Drug 2: 300 mg bid. Drug 3: 1,200 mg
                          bid. [AS PER AMENDMENT 11/9/00: 600 mg bid.]
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: [AS PER AMENDMENT
                          11/9/00: Arm B: 200 mg, except no dosthe
                          background regimen contains RTV. If the
                          background regimen contains EFV, dose is 400
                          mg.] Drug 2: 600 mg. Drug 3: 2,400 mg. [AS
                          PER AMENDMENT 11/9/00: 1200 mg.]
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Primary endpoint: Plasma HIV-1 RNA
                          levels below 500 copies/ml at Week 24;
                          virology, pharmacology, and immunology
                          studies are conducted at the end of the
                          study, Week 48.
OTHER TREATMENT INFO.     DISCONTINUE: Patients may discontinue study
                          treatment for the following reasons: 1.
                          Drug-related toxicities as outlined in the
                          protocol [AS PER AMENDMENT 11/9/00: resulting
                          in permanent discontinuation of study drugs
                          or any component of background ART for
                          greater than 28 days. Changes to background
                          ART will be allowed provided that the new
                          background ART is still a potent,
                          PI-containing ART comprising at least 3
                          drugs. [AS PER AMENDMENT 04/03/01: ART need
                          not contain a PI.] The protocol chair/vice
                          chairs must approve any changes to the
                          background ART.] 2. Failure to attend more
                          than 3 consecutive clinic visits or failure
                          to take study medications as prescribed
                          without reasonable cause, as determined by
                          the investigator. 3. Requirement for
                          disallowed medications or systemic therapy
                          for treatment of a malignancy. 4. Any
                          clinical reason that is life-threatening to
                          the patient, as determined by the
                          investigator. 5. Pregnancy. [6. AS PER
                          AMENDMENT 11/9/00: Plasma HIV-1 RNA greater
                          than 10,000 copies/ml and confirmed within 30
                          days.] Note: If a patient must permanently
                          discontinue 1 study medication for which
                          there is no substitution, all study
                          medications are permanently discontinued for
                          this patient. [AS PER AMENDMENT 11/9/00:
                          Substitutions for non-study antiretrovirals
                          that are discontinued will only be made with
                          the permission of the protocol chair/vice
                          chairs.].
OTHER TREATMENT INFO.     MODIFICATION: Study medications may be
                          modified as follows: If a study medication
                          must be discontinued because of toxicity,
                          appropriate FDA-approved NRTIs, such as
                          lamivudine, stavudine, zalcitabine, or
                          zidovudine (ZDV), may be substituted with
                          permission from the protocol chair or
                          vice-chairs. [AS PER AMENDMENT 11/9/00: If a
                          study medication must be discontinued because
                          of toxicity, appropriate FDA-approved
                          antiretroviral drugs may be substituted with
                          permission from the protocol chair or
                          vice-chairs.] (ZDV may not be substituted for
                          a study medication for patients in Arm C. [AS
                          PER AMENDMENT 11/9/00: Arm C has been
                          discontinued.]) Study medication may be
                          interrupted at the discretion of the
                          investigator according to the severity of an
                          adverse experience. Doses of ddI and HU may
                          be reduced, interrupted, or reintroduced
                          according to standard practice at any
                          time.[AS PER AMENDMENT 11/9/00: ddI and HU
                          have been discontinued.] ABC and APV may be
                          interrupted or stopped but not dose-reduced.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Betty
                          McCulloch [phone] Recruiting 010103.
CALIFORNIA                Univ of California San Diego UCSD Treatment
                          Center / 150 West Washington St Suite 100 San
                          Diego, CA 92103 Jill Kunkel [phone]
                          Recruiting 010723.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 010103.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 010318.
MASSACHUSETTS             Beth Israel Deaconess - West Campus One
                          Deaconess Rd / Kennedy Building 6th Floor
                          Boston, MA 02215 Helen Fitch [phone]
                          Recruiting 010316.
MISSOURI                  St Louis Regional Hosp / St Louis Regional
                          Med Ctr 5535 Del Mar / West Annex / 6th Floor
                          St Louis, MO 63112 Michael Klebert
                          [phone] Recruiting 010103.
NORTH CAROLINA            Duke Univ Med Ctr Hosp South / PO Box 3284
                          Durham, NC 27710 Paulette MacDougall
                          [phone] Recruiting 010207.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 010103.
TEXAS                     Univ of Texas Galveston AIDS Clinical Trials
                          Unit / 301 University Blvd Galveston, TX
                          775550435 Karen Waterman [phone] No
                          longer recruiting 010501.

101
UNIQUE IDENTIFIER         NIH/01213
PROTOCOL ID NUMBERS       NIAID HIVNET 014A
PROTOCOL TITLE            Evaluation of Virologic, Immunologic, and
                          Clinical Parameters of Participants in HIVNET
                          014 Who Become Infected with HIV-1.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To evaluate the long-term (5 years
                          or more) immunologic, virologic, and clinical
                          parameters of candidate HIV-vaccine or
                          placebo recipients who become HIV-1 infected
                          after enrollment in HIVNET 014 (A Phase II
                          Safety and Immunogenicity Trial of Live
                          Recombinant Canarypox ALVAC-HIV vCP205 With
                          or Without HIV-1 SF-2 rgp120), also known as
                          AVEG 202.
GENERAL DESCRIPTION       RATIONALE: There are many possible outcomes
                          of HIV-1 infection among persons who receive
                          experimental HIV-1 vaccines. In the best-case
                          scenario, these vaccines may prevent
                          infection (sterilizing immunity). However,
                          current viral vaccines are thought to limit,
                          but not prevent, virus replication after
                          infection. In the latter case, it is
                          important to document the effect of the
                          immune response on the disease course as
                          reflected by viral load, the evolution of the
                          viral quasi species, and clinical symptoms
                          over time. Understanding the evolution of the
                          immune response in vaccinees after subsequent
                          exposure and HIV infection will potentially
                          result in valuable information for the
                          subsequent design of preventive and
                          therapeutic vaccines. This will be studied
                          here using HIVNET 014 participants at higher
                          risk for HIV-1 infection.
GENERAL DESCRIPTION       METHODOLOGY: Participants discontinue HIVNET
                          014 vaccinations upon confirmation of HIV-1
                          infection and are enrolled in this study.
                          Participants undergo clinical and laboratory
                          examinations every 3 months for the first
                          year of follow-up and every 6 months for at
                          least 4 years thereafter. Additionally,
                          HIV-infected partners of HIVNET 014A
                          participants undergo clinical and laboratory
                          examination at enrollment, and may be asked
                          to donate additional specimens at a later
                          time. Study endpoints include various
                          virologic, immunologic, and clinical
                          parameters, such as viral load, cellular
                          immune response, and virus phenotype and
                          genotype.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Immunology, Clinical
                          Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 5
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 9/ 000412.
PROTOCOL DETAILS          STUDY DURATION: At least 5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 11
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (980929)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: HIV infection, as confirmed in HIVNET
                          014, or identification as a HIVNET 014A
                          participant's HIV-infected sexual or
                          needle-sharing partner. (Note: Pregnant or
                          lactating women who are unable to tolerate
                          the study requirements and/or who have poor
                          venous access will have modifications of the
                          blood draw requirements to allow them to
                          participate safely.).
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed:
                          Antiretroviral or immunomodulatory therapy.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 60 years.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Obvious
                          psychological/psychiatric disorder that would
                          invalidate the informed consent process, or
                          otherwise contraindicate participation in the
                          study.
OTHER TREATMENT INFO.     END POINT: Various virologic, immunologic,
                          and clinical parameters, such as viral load,
                          cellular immune response, and virus phenotype
                          and genotype.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                San Francisco Dept of Hlth / AIDS Office 25
                          Van Ness Ave / Suite 500 San Francisco, CA
                          94102 Joe Wright [phone] Recruiting
                          991122.
COLORADO                  Denver Dept of Public Health / HIVNET 605
                          Bannock St / Room 220 Denver, CO 80204 Frank
                          Judson [phone] Recruiting 991122.
ILLINOIS                  Univ of Illinois Chicago / Howard Brown Hlth
                          Ctr Division of Infectious Diseases / 808
                          South Wood St Chicago, IL 60612 Fred Swanson
                          [phone] Recruiting 991122.
ILLINOIS                  Howard Brown Health Ctr / HIVNET 945 West
                          George St Chicago, IL 60657 Recruiting
                          991122.
MASSACHUSETTS             Fenway Community Health Ctr / HIVNET 7
                          Haviland St Boston, MA 02115 Kenneth Mayer
                          [phone] Recruiting 991122.
NEW YORK                  New York Blood Ctr Project ACHIEVE / 1309
                          Fulton Ave Room 312 Bronx, NY 10456
                          Recruiting 991122.
NEW YORK                  New York Univ Med Ctr 650 First Ave 5th Floor
                          New York, NY 10016 Jose Claudio [phone]
                          Recruiting 991122.
PENNSYLVANIA              Univ of Pennsylvania / HIVNET RAP Office /
                          521-523 West Girard Ave Philadelphia, PA
                          19104 Cynthia Clark [phone] Recruiting
                          991122.
RHODE ISLAND              Miriam Hosp 164 Summit Ave Providence, RI
                          02906 Recruiting 991122.
RHODE ISLAND              Mem Hosp of Rhode Island 111 Brewster St
                          Pawtucket, RI 02860 Tom LaSalvia
                          [phone] Recruiting 991122.
WASHINGTON                Univ of Washington 901 Boren Ave Suite 1300
                          UW Box 3599227 Seattle, WA 98104 Dennis
                          Torres [phone] Recruiting 991122.

102
UNIQUE IDENTIFIER         NIH/01210
PROTOCOL ID NUMBERS       NIAID AIEDRP AI-02-001
PROTOCOL TITLE            A Study of the Effects of Combination
                          Antiretroviral Therapy in Acute HIV-1
                          Infection with an Emphasis on Immunological
                          Responses.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To determine the following in
                          patients with acute HIV-1 infection treated
                          with [AS PER AMENDMENT 9/15/00: 1 of 2]
                          potent antiretroviral therapy [AS PER
                          AMENDMENT 9/15/00: therapies] (ART): 1. The
                          safety and tolerability of [AS PER AMENDMENT
                          9/15/00: these] potent combination ART [AS
                          PER AMENDMENT 9/15/00: ARTs]. 2. The
                          immunological responses to HIV-1 as measured
                          by: CD4+ and CD8+ T cell subsets;
                          quantitative assessments of envelope-, gag-,
                          nef-, and pol-specific cytotoxic T lymphocyte
                          (CTL) activity; V beta perturbation; and
                          neutralizing antibodies to prototype and
                          autologous strains. 3. The proportion of
                          patients who have plasma HIV-1 RNA below 50
                          copies/ml by Roche Ultrasensitive Assay. 4.
                          The quantity of proviral DNA in PBMCs. 5.
                          Response rates to hepatitis B surface
                          antigen, in patients who have not had
                          hepatitis B infection, compared with
                          responses in HIV+ and HIV- controls. 6.
                          Response rates and antibody titer after
                          tetanus vaccination compared with responses
                          in HIV+ and HIV- controls.
GENERAL DESCRIPTION       RATIONALE: Current treatment guidelines
                          recommend combination ART for acute primary
                          HIV-1 infection. However, it is not known
                          whether ART given during acute infection
                          delays progression to AIDS or improves
                          survival rates. Preliminary studies suggest
                          ART given early in HIV infection not only
                          reduces viral load but also restricts CD4+
                          cell loss, delays the development of
                          opportunistic infections, and preserves
                          T-helper cells and naive T cells. The
                          immunologic basis of these protective effects
                          has not been characterized thoroughly. This
                          protocol assesses ART's effects on immune
                          responses in early HIV infection through a
                          variety of cellular, humoral, and virologic
                          assays, including 2 substudies. The
                          substudies focus on antibody responses to
                          neoantigen immunization (hepatitis B and
                          tetanus). Primary endpoint analysis occurs at
                          Week 72, but patients may be followed for
                          long-term outcomes.
GENERAL DESCRIPTION       METHODOLOGY: In the main study, patients with
                          HIV-1 infection of less than 120 days are
                          given the option of taking a potent ART
                          combination of abacavir (ABC), efavirenz
                          (EFV), indinavir (IDV), and lamivudine (3TC)
                          for 96 weeks. [AS PER AMENDMENT 9/15/00:
                          Patients choose either Regimen 1: ABC, 3TC,
                          IDV, and ritonavir (RTV) or Regimen 2: ABC,
                          3TC, and EFV.] Patients who decline treatment
                          provide a concurrent, non-randomized
                          comparison group. These patients may choose
                          to be considered for study treatment at any
                          time or to start antiretrovirals provided
                          through another source. [AS PER AMENDMENT
                          9/15/00: If a patient who initially does not
                          start therapy subsequently starts
                          antiretroviral therapy provided by the study
                          (within the 120-day limit), the visit
                          schedule is re-set.] During the treatment
                          period, all patients undergo regular physical
                          exams and blood tests to characterize T
                          cells, viral resistance, antibody responses,
                          and other markers. Patients presenting within
                          30 days of HIV-1 infection undergo
                          leukapheresis (where available) prior to
                          starting ART. At Month 12, these patients and
                          all untreated patients undergo leukapheresis
                          to assess the proportion of latently infected
                          CD4+ T cells. In addition, all patients in
                          the main study and patients in 2 comparison
                          groups (Cohorts A and B) participate in 1 of
                          2 substudies of antibody responses to
                          neoantigen. Volunteers are recruited to 2
                          cohorts to serve as controls. Cohort A
                          volunteers have established HIV-1 infection.
                          Cohort B volunteers are HIV-1 seronegative
                          but at high risk for HIV. In the first
                          substudy, hepatitis B-seronegative patients
                          from the main study and from Cohorts A and B
                          receive hepatitis B vaccine at Weeks 40, 44,
                          and 64 and undergo humoral and cellular
                          response assessments at Week 68. In the
                          second substudy, patients from the main study
                          and from Cohorts A and B who did not qualify
                          for the hepatitis B vaccination undergo
                          intramuscular vaccination with tetanus toxoid
                          at Week 64 and immune responses are assessed
                          at Week 68. Volunteers in Cohorts A and B
                          receive no anti-HIV medication as part of
                          these substudies.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010730)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety, Drug therapy,
                          Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 288 patients. Main study:
                          140 patients with acute HIV-1 infection.
                          Substudies: 94 patients with chronic HIV-1
                          infection in Cohort A. 54 HIV-1 seronegat
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 96 weeks with
                          possible extension of 48 weeks or more.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 24/288 010731.
PROTOCOL DETAILS          STUDY DURATION: If the data warrant, the
                          study may be extended to follow patient
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 11
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (001013)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Case-Control Study; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients in the
                          main study must have: 1. HIV-1 infection of
                          less than 120 days duration, as evidenced by
                          positive plasma HIV-1 RNA assay and negative
                          HIV-1 enzyme immunoassay (EIA) with the
                          duration of infection defined as the time
                          since the onset of symptoms, or as evidenced
                          by positive HIV-1 antibody test and negative
                          HIV-1 EIA within the past 240 days (midpoint
                          less than 120 days) [AS PER AMENDMENT
                          9/15/00: or confirmed HIV-1 antibody positive
                          with a negative detuned HIV-1 antibody
                          test]. 2. Written informed consent of parent
                          or guardian if under age 18. 3. Availability
                          for at least 72 weeks of follow-up. Patients
                          in substudy Cohort A must have: 1. HIV-1
                          infection of more than 1 year's duration, as
                          documented by a confirmed HIV-1 antibody test
                          or history of positive HIV-1 antibody test of
                          more than 1 year ago, provided patient's
                          account is judged reliable. 2. CD4+ T cell
                          count greater than 500 cells/mm3 within past
                          60 days. 3. Availability for a minimum of 8
                          weeks for the tetanus vaccination study or 28
                          weeks for the hepatitis B vaccine study. 4.
                          Written informed consent from a parent or
                          guardian if under 18. 5. Seronegativity to
                          markers for hepatitis B virus (HBsAg,
                          anti-HBsAg, anti-HBcAg). This criterion only
                          applies to patients receiving the hepatitis B
                          vaccine. Patients in substudy Cohort B must
                          have: 1. HIV-1 seronegativity by EIA. 2.
                          Acknowledgment of behavior recognized to
                          transmit HIV-1 (including sexual activity or
                          injection drug use) within the past year. 3.
                          Availability for a minimum of 8 weeks for the
                          tetanus vaccination study or 28 weeks for the
                          hepatitis B vaccine study. 4. Written
                          informed consent from a parent or guardian if
                          under 18. 5. Seronegativity to markers for
                          hepatitis B virus (HBsAg, anti-HBsAg,
                          anti-HBcAg). This criterion applies only to
                          patients receiving the hepatitis B vaccine.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl for women, >= 9.0
                          g/dl for men. Required for patients in main
                          study group only.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3 Required for
                          patients in main study group only.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 500 cells/mm3 Required
                          for patients in Cohort A only.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN ULN (Upper Limit of
                          Normal). Required for patients in main study
                          group only.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN Required for patients in
                          main study group only.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN Required for patients in
                          main study group only.
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN Required for patients
                          in main study group only.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Negative
                          pregnancy test within 14 days of study entry.
PATIENT INCLUSION CRIT.   RISK BEHAVIOR: Required for substudy Cohort
                          B: Acknowledgment of behavior recognized to
                          transmit HIV-1 (including sexual activity or
                          injection drug use) within the past year.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed with caution
                          for patients on the initial drug regimen in
                          the main study: Medications that interact at
                          CYP3A4, either as substrates, inhibitors, or
                          inducers of the enzyme, including but not
                          limited to amiodarone, benzodiazepines,
                          calcium channel blockers,
                          cholesterol-lowering agents, carbamazepine,
                          codeine, cimetidine, dapsone, erythromycin,
                          estrogen and progestogens, glucocorticoids,
                          systemic lidocaine, phenobarbital, phenytoin,
                          quinidine, tricyclic antidepressants, and
                          warfarin. Allowed with caution for patients
                          receiving amprenavir (APV) in the main study:
                          Antibiotics, anticonvulsants, antifungals,
                          benzodiazepines, calcium channel blockers,
                          cholesterol-lowering agents [AS PER AMENDMENT
                          9/15/00: including simvastatin],
                          nonnucleoside reverse transcriptase
                          inhibitors, opiate antagonists, steroids,
                          clozapine, loratadine, pimozide, cimetidine,
                          ritonavir, antacids, and didanosine. Allowed
                          with caution for patients on indinavir in the
                          main study: Statin drugs that are metabolized
                          by the cytochrome p450 3A4 pathway.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 16
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following symptoms or conditions are excluded
                          from substudy Cohorts A and B: 1. History of
                          hepatitis B infection. This criterion applies
                          only to patients receiving the hepatitis B
                          vaccine. 2. Severe reaction to prior tetanus
                          vaccination. This criterion applies only to
                          patients receiving the tetanus vaccine.
                          Patients with the following symptoms or
                          conditions are excluded from substudy Cohort
                          B: History of HIV-1 infection or clinical
                          suspicion of acute HIV-1 infection within the
                          past 6 months. (Patients with a clinical
                          suspicion of acute HIV-1 infection more than
                          6 months ago who did not acquire HIV-1 are
                          eligible.).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded from the main
                          study: 1. More than 7 days of antiretroviral
                          therapy for treatment of HIV-1 infection.
                          (Patients who received antiretroviral therapy
                          for post-exposure prophylaxis of HIV-1 and
                          who still developed HIV-1 infection are
                          eligible.) 2. More than 72 hours of
                          immunomodulators for treatment of HIV-1
                          infection. 3. Experimental therapy within 30
                          days prior to study entry. Excluded from
                          substudy Cohorts A and B: 1. Experimental
                          therapy within 14 days prior to study entry.
                          2. Prior hepatitis B vaccine. This criterion
                          applies only to patients receiving the
                          hepatitis B vaccine. 3. Tetanus vaccine
                          within the past 5 years. This criterion
                          applies only to patients receiving the
                          tetanus vaccine.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded from the main
                          study: 1. Any experimental therapy that, in
                          the opinion of the investigator,
                          significantly interferes with compliance with
                          the protocol or interpretation of the
                          results. 2. Astemizole, bepridil, cisapride,
                          ergotamine/dihydroergotamine-containing
                          drugs, ketoconazole, midazolam, rifabutin,
                          rifampin, sildenafil, terfenadine, or
                          triazolam for patients on standard study drug
                          regimen. 3. Amiodarone, bupropion,
                          clorazepate, clozapine, diazepam, encainide,
                          estazolam, flecainide, flurazepam,
                          meperidine, pimozide, piroxicam, propafenone,
                          propoxyphene, quinidine, rifabutin, and
                          zolpidem for patients on ritonavir. 4.
                          Vitamin E for patients on APV. [5. AS PER
                          AMENDMENT 9/15/00: Simvastatin should not be
                          used by patients taking a protease inhibitor
                          (IDV, RTV, or APV).] Excluded from substudy
                          Cohorts A and B: Any experimental therapy
                          that, in the opinion of the investigator,
                          significantly interferes with compliance with
                          the protocol or interpretation of t
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded from the main study:
                          1. Any condition that, in the opinion of the
                          investigator, significantly interferes with
                          compliance with the protocol or
                          interpretation of the results. 2. Malignancy
                          that requires systemic therapy. 3.
                          Hypersensitivity to ABC, EFV, IDV, or 3TC.
                          Excluded from substudy Cohorts A and B: 1.
                          Any condition that, in the opinion of the
                          investigator, significantly interferes with
                          compliance with the immunization protocol or
                          interpretation of the results. 2. Malignancy
                          that requires systemic therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0269  Lamivudine/Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0126  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0004  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0258  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0142  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0285  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 8  DRG-0233  Amprenavir
SUBSTANCE IDENTIFICATION  Drug 9  DRG-0244  Hepatitis B Vaccine
                          (Recombinant)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 300 mg bid. Drug 2:
                          600 mg qd (recommended to be taken at
                          bedtime). Drug 3: 150 mg bid. Drug 4: 300 mg
                          bid or 200 mg bid if intolerant to initial
                          regimDrug 5: 1,200 mg bid or 600 mg bid (if
                          taking with ritonavir) iintolerant to initial
                          regimen. Drug 6: Hepatitis B Vaccine
                          substudy: qualified patients from tmain
                          study, Cohort A, and Cohort B, 10 microg at
                          Weeks 40, 44, 64. Drug 7: Zidovudine 300
                          mg/lamivudine 150 mg bid if intolerant
                          tinitial regimen. Drug 8: 800 mg bid. Drug 9:
                          100 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 600 mg.
                          Drug 3: 300 mg. Drug 4: 600 mg or 400 mg if
                          intolerant to initial regimen. Drug 5: 2,400
                          mg or 1,200 mg (if taking with ritonavir) if
                          intolerant to initial regimen. Drug 6: N/A
                          Drug 7: Zidovudine 600 mg/lamivudine 300 mg
                          if intolerant to inregimen. Drug 8: 1,600 mg.
                          Drug 9: 200 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral. Drug 5: Oral.
                          Drug 6: Intramuscular. Drug 7: Oral. Drug 8:
                          Oral. Drug 9: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 96 weeks with possible
                          extension of 48 weeks or more.
OTHER TREATMENT INFO.     END POINT: Virologic status and immunological
                          function of patients in main study at Week
                          72.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue the study
                          for the following reasons: 1. Pregnancy. 2.
                          Failure to attend multiple clinic visits for
                          unexplained reasons or repeated failure to
                          take study medications as prescribed without
                          reasonable cause, as determined by the
                          investigator. 3. Requirement for treatment
                          medications that are disallowed. 4. Drug
                          toxicity. 5. Clinical reasons which, in the
                          opinion of the investigator, are life
                          threatening. Note: Any and all study
                          medications may be interrupted or permanently
                          discontinued for drug-related toxicity
                          without discontinuation from the study. [AS
                          PER AMENDMENT 9/15/00: If a patient must
                          interrupt 1 or more study drugs without
                          substituting another antiretroviral, all
                          study medications should be temporarily
                          discontinued.].
OTHER TREATMENT INFO.     MODIFICATION: Study drugs may be modified as
                          follows: The only drug [AS PER AMENDMENT
                          9/15/00: provided by the study] for which
                          there will be a dose adjustment for toxicity
                          is ZDV.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010730
CALIFORNIA                San Francisco Dept of Hlth / AIDS Office 25
                          Van Ness Ave / Suite 500 San Francisco, CA
                          94102 Grant Colfax MD [phone]
                          Recruiting 991018.
ILLINOIS                  Univ of Illinois Chicago / Howard Brown Hlth
                          Ctr Division of Infectious Diseases / 808
                          South Wood St Chicago, IL 60612 Fred Swanson
                          [phone] Recruiting 991018.
MASSACHUSETTS             Fenway Community Health Ctr / HIVNET 7
                          Haviland St Boston, MA 02115 Lorraine Schieve
                          [phone] Recruiting 000509.
MINNESOTA                 Univ of Minnesota 420 Delaware St SE / Box
                          250 Minneapolis, MN 55455 Chuck Sieber
                          [phone] Recruiting 000404.
NEW YORK                  Bronx-Lebanon Hosp Ctr Vaccine Trial Site /
                          1645 Grand Concourse Suite 1G Bronx, NY 10453
                          Elizabeth Doramajian [phone] Recruiting
                          991018.
NEW YORK                  New York Univ Med Ctr 650 First Ave 5th Floor
                          New York, NY 10016 Cynthia Harrison
                          [phone] Recruiting 991018.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] Recruiting 991018.
OTHER                     Saint Vincent's Hosp Med Centre 376 Victoria
                          St / 2nd Floor Darlinghurst, David A Cooper
                          MD (293)324-648 Recruiting 991018.
RHODE ISLAND              Mem Hosp of Rhode Island 111 Brewster St
                          Pawtucket, RI 02860 Susan Kelley
                          [phone] Recruiting 991018.
WASHINGTON                Fred Hutchinson Cancer Research Ctr 1100
                          Fairview Ave N / PO Box 19024 Seattle, WA
                          98109 Theresa Shea [phone] Recruiting
                          991018.
WASHINGTON                Univ of Washington 901 Boren Ave Suite 1300
                          UW Box 3599227 Seattle, WA 98104 Manuel
                          Ramirez [phone] Recruiting 991018.

103
UNIQUE IDENTIFIER         FDA/01205
PROTOCOL ID NUMBERS       FDA 039F
PROTOCOL TITLE            Evaluation of HIV RNA Suppression Produced by
                          a Triple Combination Regimen Containing an
                          Enteric Coated Formulation of Didanosine (ddI
                          EC) Administered Once Daily Compared to a
                          Reference Combination Regimen.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To show that the antiviral activity
                          of the triple combination regimen of ddI EC
                          plus stavudine (d4T) plus nelfinavir (NFV) is
                          similar to that produced by Combivir
                          (zidovudine [ZDV] plus lamivudine [3TC]) plus
                          NFV. Methodology: Patients are randomized to
                          1 of 2 groups for 48 weeks of open-label
                          treatment. Group 1 receives ddI EC plus d4T
                          plus NFV. Group 2 receives Combivir plus NFV.
                          Antiviral activity is determined by the
                          proportion of patients with HIV RNA levels of
                          less than 400 copies/ml at Week 48.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to 1 of
                          2 groups for 48 weeks of open-label
                          treatment. Group 1 receives ddI EC plus d4T
                          plus NFV. Group 2 receives Combivir plus NFV.
                          Antiviral activity is determined by the
                          proportion of patients with HIV RNA levels of
                          less than 400 copies/ml at Week 48.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (000815)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 500 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks after
                          enrollment of last patient.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/500.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 23
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AI454-152
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation; Parallel Designs
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Plasma HIV RNA count of at least
                          2,000 copies/ml and CD4 cell count of at
                          least 200 cells/mm3 within 3 weeks prior to
                          randomization. 2. Availability for at least
                          16 weeks of follow-up.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 200 cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   OTHER: Total serum lipase: <= 1.4 x ULN.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Negative pregnancy test within 3 days
                          prior to study entry.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Strongly recommended:
                          Prophylaxis for Pneumocystis carinii
                          pneumonia (PCP) for patients with CD4 cell
                          counts less than 200 cells/mm3 or a history
                          of PCP. Allowed: 1. Immunizations. 2.
                          Erythropoietin and/or G-CSF for bone-marrow
                          suppression emerging on study.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Intractable diarrhea (at least 6 loose
                          stools/day for more than 7 consecutive days)
                          within 30 days prior to study entry. 2.
                          History of acute or chronic pancreatitis. 3.
                          Proven or suspected acute hepatitis within 30
                          days prior to study entry.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          substance abuse that, as determined by the
                          study investigator, is sufficient to prevent
                          adequate compliance with study therapy or to
                          increase the risk of developing pancreatitis.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Previous
                          therapy with agents with significant systemic
                          myelosuppressive, neurotoxic, pancreatotoxic,
                          hepatotoxic, or cytotoxic potential within 3
                          months of study start. 2. Any antiretroviral
                          therapy. (Note: Up to 4 weeks of nucleoside
                          therapy and up to 1 week of protease
                          inhibitor therapy are allowed provided both
                          therapies are stopped at least 14 days prior
                          to randomization.).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Agents
                          with significant systemic myelosuppressive,
                          neurotoxic, pancreatotoxic, hepatotoxic, or
                          cytotoxic potential. 2. Potent neurotoxic
                          drugs, such as vincristine and thalidomide.
                          3. Certain drugs affecting CYP 3A4.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Presence of a newly diagnosed AIDS-defining
                          opportunistic infection requiring acute
                          therapy at the time of enrollment. 2.
                          Bilateral peripheral neuropathy or signs and
                          symptoms of bilateral peripheral neuropathy
                          of at least Grade 2 at the time of screening.
                          3. Inability to take oral medication. 4. Any
                          other clinical conditions or prior therapy
                          that, in the opinion of the investigator,
                          would make the patient unsuitable for study
                          or unable to comply with dosing requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0285  Lamivudine/Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0263  Nelfinavir mesylate
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral,
                          enteric coated formulation. Drug 3: Oral.
                          Drug 4: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
SUPPORTING AGENCY         Bristol - Myers Squibb Pharmaceutical
                          Research Institute.
LAST REVISION DATE        20000815
ALABAMA                   Sorra Research Ctr / Med Forum 950 N 22nd St
                          / Suite 550 Birmingham, AL 35203 Bonnie
                          Brewer [phone] Recruiting 990708.
ARIZONA                   Body Positive 4021 N 30th St Phoenix, AZ
                          85016 Barbara Kasimir [phone]
                          Recruiting 990708.
CALIFORNIA                AIDS Healthcare Foundation 1300 North Vermont
                          Ave Los Angeles, CA 900276069 Euny Kim
                          [phone] Recruiting 990708.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave San
                          Francisco, CA 94115 Dorie Heeren
                          [phone] Recruiting 990708.
FLORIDA                   County Line Med CtrInc 4065 SW 40th Ave
                          Pembrook, FL 33023 Dennis Rosa-Re
                          [phone] Recruiting 990708.
FLORIDA                   Dr Gerald Pierone Jr 3715 7th Terrace Vero
                          Beach, FL 32960 Jeff Mieras [phone]
                          Recruiting 990708.
FLORIDA                   Med Alternatives 2480 East Commercial Blvd /
                          Suite #2 Fort Lauderdale, FL 33308 Fausto
                          Capella [phone] Recruiting 990708.
ILLINOIS                  The CORE Ctr 2020 West Harrison St Chicago,
                          IL 60612 Marisol Gonzalez [phone]
                          Recruiting 990708.
INDIANA                   Indiana Univ Med Ctr 550 N Univ Blvd / Room
                          5550 Indianapolis, IN 462025250 Beth Zwickle
                          [phone] Recruiting 990708.
KANSAS                    Univ of Kansas School of Medicine 1010 North
                          Kansas St Wichita, KS 672143124 Janice
                          Cerrulo [phone] Recruiting 990708.
MICHIGAN                  Henry Ford Hosp Div of Infect Diseases / 2799
                          West Grand Blvd / CFP 106 Detroit, MI 48202
                          Diane Smith [phone] Recruiting 990708.
NEW HAMPSHIRE             Dartmouth-Hitchcock Med Ctr 1 Med Ctr Dr /
                          Clinic 3D Lebanon, NH 03756 Donna Alvarenga
                          [phone] Recruiting 990708.
NEW JERSEY                Infectious Disease Assoc of Central Jersey
                          411 Courtyard Dr Somerville, NJ 08876 Larry
                          Hocking [phone] Recruiting 990708.
NEW JERSEY                NJCRI 393 Central Ave / Suite 301 Newark, NJ
                          07103 Kerry Gristi [phone] Recruiting
                          990708.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] Recruiting 990708.
OTHER                     Clinique Medicale du Quartier Latin 905 Boul
                          Rene Levesque Est Montreal, QC Denise
                          LaFreniere [phone] Recruiting 990708.
OTHER                     Dr Roger P Leblanc 3545 Chemin Cote des
                          Neiges / Suite 023 Montreal, QC Francois
                          Lanteigne (514) 93-5 1197 Recruiting 990708.
OTHER                     Clinique Medicale L'Actuele 1001 de
                          Maisonneuve est / bureau 1130 Montreal, QC
                          Luc Gagnon [phone] Recruiting 990708.
PENNSYLVANIA              Anderson Clinical Research 3339 Ward St
                          Pittsburgh, PA 15213 Monica Earnest
                          [phone] Recruiting 990708.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75235
                          Claudia Quittner [phone] Recruiting
                          990708.
TEXAS                     Montrose Clinic 215 Westheimer Rd Houston, TX
                          77006 Barbara Buckhardt [phone]
                          Recruiting 990708.
TEXAS                     Joseph Gathe Private Practice 1200 Binz St /
                          Suite 120 Houston, TX 77004 Dorothy Bartley
                          [phone] Recruiting 990708.
VIRGINIA                  Hampton Roads Med Specialists 2112 Executive
                          Dr Hampton, VA 23666 Lois Hulman
                          [phone] Recruiting 990708.

104
UNIQUE IDENTIFIER         NIH/01201
PROTOCOL ID NUMBERS       NIAID ACTG 723
PROTOCOL TITLE            Effect of Highly Active Antiretroviral
                          Therapy (HAART) on Viral Burden and Immune
                          Function in the Lungs of HIV-Infected
                          Subjects.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: Blood tests and bronchoalveolar
                          lavage (BAL) are used to evaluate whether:
                          (1) HIV viral load in BAL cells and fluid
                          correlates with viremia; (2) HAART reduces
                          HIV viral load in BAL cells and fluid; and
                          (3) HAART reduces the intensity of
                          lymphocytic alveolitis in HIV-infected
                          patients. No drugs are provided through this
                          study.
GENERAL DESCRIPTION       RATIONALE: Lymphocytic alveolitis in
                          HIV-infected patients probably represents a
                          local immune response to HIV-infected cells
                          in the lung. The intensity of lymphocytic
                          alveolitis may therefore reflect the viral
                          load in the lung. If so, treatment that
                          reduces viral load in the lung (e.g., HAART)
                          should also decrease the number of cytotoxic
                          T lymphocytes (CTLs) in the alveolar space
                          and should return pulmonary immune responses
                          toward normal.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified by CD4
                          count: less than 200 cells/mm3 or 200 - 500
                          cells/mm3. BAL is performed and blood samples
                          are collected prior to initiation of HAART
                          and after 1 and 6 months of HAART. If a
                          patient has detectable HIV in the lung after
                          6 months of HAART, the patient is asked to
                          submit to an optional fourth BAL after 12
                          months of HAART. BAL fluid and cells are
                          analyzed for HIV viral load, percent
                          lymphocytes, and lymphocyte subsets.
                          Responses in the lung are compared to
                          simultaneous changes in these variables found
                          in the peripheral blood. Each patient serves
                          as his/her own control.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Immunology, Clinical
                          Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 50 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 6 - 12 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 22/50 010724.
PROTOCOL DETAILS          STUDY DURATION: 12 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG 723
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV culture, HIV
                          antigen, plasma HIV RNA, or a second antibody
                          test by a method other than ELISA at any time
                          prior to study entry. 2. No prior exposure to
                          protease inhibitors (PIs) or non-nucleoside
                          reverse transcriptase inhibitors (NNRTIs),
                          and must be about to begin HAART. 3. CD4
                          lymphocyte count of less than or equal to 500
                          cells/mm3 within 30 days prior to study entry
                          as measured by a certified ACTG laboratory.
                          4. Plasma HIV RNA copies greater than or
                          equal to 5000 copies/ml within 30 days prior
                          to study entry as measured by any laboratory
                          certified for the Roche Amplicor HIV-1
                          Monitor or the Roche UltraSensitive assay.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 500 cells/mm3.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: HAART
                          (defined as at least 3 antiretroviral drugs).
                          This can be, but is not mandated to be, an
                          AACTG treatment protocol.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Signs or symptoms of pulmonary disease within
                          the past 30 days (pneumonia, bronchitis,
                          emphysema, asthma exacerbations, chronic
                          cough, or chronic shortness of breath).
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Prisoners.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior exposure
                          to protease inhibitors (PIs) or
                          non-nucleoside reverse transcriptase
                          inhibitors (NNRTIs). 2. Prior exposure to
                          immunomodulatory therapies (HIV vaccines,
                          IL-2, IL-12, cytokines, TNF antibodies,
                          prednisone, or cyclosporin). 3. Any
                          experimental therapies (drugs or vaccines)
                          within 30 days prior to study entry. 4.
                          Systemic cytotoxic chemotherapy within 30
                          days prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Any
                          malignancy requiring systemic chemotherapy.
OTHER TREATMENT INFO.     END POINT: 0.5 log reduction of HIV RNA in
                          BAL fluid and inducible HIV in alveolar
                          macrophages (AM).
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Inability to
                          tolerate a HAART regimen for 6 months of
                          therapy. (Patients may be switched to other
                          HAART regimens without discontinuing from
                          ACTG 723.) 2. Inability or refusal to
                          complete scheduled BALs per protocol. 3.
                          Pregnancy beyond the first trimester by Week
                          24. (Note: If a patient becomes pregnant
                          while on study and their HAART regimen is
                          continued at the discretion of the treating
                          physician, they may continue on ACTG 723
                          provided the scheduled BALs can be completed
                          within the first trimester of pregnancy.).
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd / Room
                          0674 Indianapolis, IN 462025250 Beth Zwickl
                          [phone] Recruiting 990921.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 990930.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] No longer recruiting 001219.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 991015.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000210.

105
UNIQUE IDENTIFIER         NIH/01196
PROTOCOL ID NUMBERS       NIAID ACTG P1006
PROTOCOL TITLE            The Effects of Highly Active Antiretroviral
                          Therapy (HAART) on the Recovery of Immune
                          Function in HIV-Infected Children.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To assess the ability of newly
                          derived CD4 T cells to spontaneously develop
                          lymphoproliferative responses to a recall
                          antigen, tetanus toxoid, or to develop
                          responses after booster vaccinations with
                          tetanus vaccine. To assess the ability to
                          develop protective antibody responses to a T
                          cell-dependent antigen using a primary series
                          of hepatitis A vaccinations. To measure the
                          durability of any response beyond the last
                          vaccination.
GENERAL DESCRIPTION       RATIONALE: HIV-infected children initiating
                          HAART have shown significant inhibition of
                          HIV growth and significant increases in CD4 T
                          cell counts. It is not known to what extent
                          an increase in CD4 count in this population
                          of children translates to a complete
                          functional immune recovery. HIV-infected
                          children have typically demonstrated poor
                          serological responses to routine childhood
                          immunizations. This study will examine the
                          phenotype of T cells regenerated post-HAART
                          initiation and will assess function by
                          evaluating T cell responses to neoantigens
                          and recall antigens. Cell-mediated immune
                          responses to an environmental antigen
                          (Candida), a recall antigen (tetanus), and a
                          primary immunogen (hepatitis A) will be
                          tested.
GENERAL DESCRIPTION       METHODOLOGY: HAART is initiated [AS PER
                          AMENDMENT 2/28/01: or altered] within 2 weeks
                          prior to entry, although HAART optimally
                          should be started [AS PER AMENDMENT 2/28/01:
                          or changed] at entry. Patients are randomized
                          into 1 of 2 groups and a baseline viral load
                          is taken either at study entry or at time of
                          initiating or changing HAART therapy. One
                          month after entry a second viral load is
                          taken. Only patients with virologic
                          suppression (defined as a greater-than-1-log
                          decrease in plasma HIV RNA copy number) [AS
                          PER AMENDMENT 2/28/01: (defined as an 0.75 or
                          greater log decrease in plasma HIV RNA copy
                          number)] continue on the study. Patients in
                          Group 1 receive tetanus toxoid (as DTaP,
                          DT-pediatric, or Td) immunizations at Weeks
                          8, 16, and 24, and hepatitis A vaccinations
                          at Weeks 32, 40, and 48. Patients in Group 2
                          receive hepatitis A vaccinations at Weeks 8,
                          16, and 24, and tetanus toxoid immunizations
                          at Weeks 32, 40, and 48. Serologic responses
                          are assessed 1 month after the first and
                          third vaccinations. Blood for
                          lymphoproliferative studies is drawn at
                          baseline, [AS PER AMENDMENT 2/28/01: 4
                          weeks,] and 1 month after the first and final
                          tetanus vaccinations. The lymphoproliferative
                          responses to Candida and hepatitis A are
                          measured concomitantly. Additional blood
                          samples are collected at specified time
                          intervals designed to establish the lag time
                          of immune recovery and identify the phenotype
                          of T cells at baseline and over time.
                          Evaluation of immune reconstitution is based
                          on CD4 T cell rise, phenotype, and function
                          as well as a significant virologic
                          suppression.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Immunotherapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients. 45 patients
                          per group.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 100 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 21/90 010731.
PROTOCOL DETAILS          STUDY DURATION: 100 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 43
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010228)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1006
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Random Allocation;
                          Parallel Designs
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have the following symptoms and conditions:
                          1. HIV-1 infection as demonstrated by: 2
                          positive viral tests (antibody, culture, PCR
                          [quantitative or qualitative], p24 antigen,
                          or ICD p24 antigen) on 2 different specimens.
                          HIV antibody tests must be determined by a
                          federally licensed ELISA. One of the 2
                          positive HIV antibody tests must be confirmed
                          by any of the confirmatory tests (Western
                          blot or IFA). If 2 viral tests (other than
                          HIV antibody) performed at a non-ACTG
                          certified laboratory prior to entry are
                          positive, patients may be enrolled and a
                          specimen sent at or before entry to an ACTG
                          certified laboratory for culture. 2. CD4
                          percent less than 10 percent [AS PER
                          AMENDMENT 2/28/01: less than 15 percent] at
                          the time of screening. 3. Consent of parent
                          or legal guardian.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant Negative
                          pregnancy test Abstinence or agree to use
                          both a barrier and a second method of birth
                          control / contraception during the study.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: [AS PER AMENDMENT 2/28/01:
                          The following requirement has been deleted:
                          Required: Three tetanus vaccines, with at
                          least 1 tetanus immunization within the past
                          5 years, and no demonstration of
                          lymphoproliferative responses to tetanus
                          toxoid.] Allowed: Immunomodulator therapy as
                          part of perinatal clinical trials or in
                          trials for HIV-exposed infants.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Patients
                          must be initiating HAART, consisting of at
                          least 3 drugs including 2 new drugs to which
                          the patient is naive. One of the drugs to
                          which the patient is naive must be a protease
                          inhibitor or a potent nonnucleoside reverse
                          transcriptase inhibitor (NNRTI) such as
                          efavirenz. Combinations of highly effective
                          drugs are encouraged. Patients are eligible
                          if HAART is initiated [AS PER AMENDMENT
                          2/28/01: or altered] within 2 weeks prior to
                          entry, although they optimally should start
                          [AS PER AMENDMENT 2/28/01: or change] therapy
                          at entry. Allowed: 1. Opportunistic infection
                          prophylaxis. 2. EPO and/or G-CSF/GM-CSF.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 02
                          years less than or equal to 17 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Patients with
                          the following prior conditions are excluded:
                          AS PER AMENDMENT 2/28/01: 1. Previous Grade 3
                          or higher adverse event to a tetanus
                          toxoid-containing vaccine. 2. Previous
                          allergic reaction to a tetanus
                          toxoid-containing vaccine.].
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Use of IVIG
                          within 6 months prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. IVIG,
                          IL-2, steroids, and other experimental immune
                          modalities or immunosuppressive medications.
                          2. Hydroxyurea.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. A
                          Grade 3 or higher clinical laboratory
                          toxicity as defined by the Division of AIDS
                          (DAIDS) Toxicity Table for Grading Severity
                          of Pediatric Adverse Experiences. A Grade 3
                          or higher toxicity for hemoglobin or absolute
                          neutrophil count after failure with EPO or
                          G-CSF/GM-CSF. 2. Active opportunistic and/or
                          bacterial infection at the time of
                          enrollment. 3. Current diagnosis of
                          malignancy. 4. Immunity to hepatitis A by
                          routine serology.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0313  Tetanus Toxoid Vaccine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0289  Hepatitis A Vaccine
                          (Inactivated)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Group 1: Weeks 8,
                          16, and 24. Group 2: Weeks 32, 40, and 48.
                          Drug 2: Group 1: Weeks 32, 40, and 48. Group
                          2: Weeks 8, 16, and 24
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Intramuscular
OTHER TREATMENT INFO.     TREATMENT DURATION: On treatment (vaccines)
                          from Week 8 to Week 48.
OTHER TREATMENT INFO.     END POINT: A Stimulation Index (SI) of at
                          least 3 on at least 2 occasions is the
                          criterion for an LPA response to tetanus,
                          positive or negative. Hepatitis A: positive
                          serologic response. Tetanus: Four-fold
                          increase over baseline in antibody titers.
                          Primary Response Variables: SI to tetanus on
                          the LPA assay, antibody titers for tetanus
                          and hepatitis A.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unable to be
                          vaccinated due to vaccine-related toxicities
                          [AS PER AMENDMENT 2/28/01: of Grade 3 or
                          higher] or for any other reasons after
                          discussion with protocol team. 2. Vaccine
                          discontinuation will occur if there is
                          discontinuation of HAART. Discontinuation of
                          HAART for any reasons, including toxicities,
                          should be discussed with the protocol team.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          000419.
ARIZONA                   Phoenix Childrens Hosp 909 East Brill Street
                          Phoenix, AZ 85006 Laura Clarke-Steffan
                          [phone] Recruiting 000914.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 000225.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 000225.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 000225.
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 000614.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Maryanne
                          Dillon [phone] Recruiting 001116.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] Recruiting 000225.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Susan Zamer
                          [phone] Recruiting 000225.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 000228.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 010109.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 000726.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 010109.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 000228.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 000225.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000225.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 000225.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 000914.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 000225.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 000524.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 000225.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 000228.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Silvia Callejas
                          [phone] Recruiting 000225.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] No longer recruiting
                          010402.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 000225.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 000524.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] No longer recruiting
                          010528.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 000228.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 000524.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          000614.
NEW YORK                  New York Hosp - Cornell Med Ctr 505 East 70th
                          St New York, NY 10021 Anne Monroe
                          [phone] Recruiting 001013.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 000225.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 000225.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 000225.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 000225.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          000225.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 000225.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 000225.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone]
                          Recruiting 000225.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 000829.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 000225.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 000225.

106
UNIQUE IDENTIFIER         NIH/01195
PROTOCOL ID NUMBERS       NIAID ACTG P1009
PROTOCOL TITLE            Mononuclear Cell Phenotyping in Normal
                          Children.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Adolescent
GENERAL DESCRIPTION       PURPOSE: To perform peripheral blood
                          lymphocyte subset phenotyping using a 3-color
                          flow cytometry panel in HIV-negative,
                          non-exposed, normal pediatric patients in
                          which race and ethnicity resemble
                          HIV-infected and/or exposed patients.
GENERAL DESCRIPTION       RATIONALE: Early in life, the cells involved
                          in immune selection differentiate into CD4+
                          and CD8+ cells. Currently there is
                          insufficient information on the cell
                          maturation and activation of these peripheral
                          blood mononuclear cell (PBMC) subsets in
                          normal children. The critical need for this
                          information has been brought about by the
                          pediatric HIV/AIDS epidemic, which requires
                          the measurement of peripheral blood CD4+ T
                          cells and other cells types for
                          interpretation of HIV disease progression.
                          The immunopathogenesis of pediatric HIV
                          infection differs from that in adults but is
                          not well understood. In order to better
                          understand HIV disease progression in
                          HIV-infected children, these PBMC subsets
                          must be studied in normal children so that
                          control values can be established.
GENERAL DESCRIPTION       METHODOLOGY: Healthy infants, children, and
                          adolescents presenting for routine care or
                          elective surgery have a single blood sample
                          obtained. Blood is used for complete blood
                          count, peripheral blood mononuclear cell flow
                          analysis for surface markers, and plasma and
                          cell storage. Demographic information
                          including age, sex, race, and ethnicity is
                          obtained at the time of the blood draw. The
                          reason for the patient's visit is also
                          documented. No study drugs are administered
                          or supplied as part of this study.
                          Statistical analysis is used to estimate the
                          median distribution of each CD4 and CD8
                          subset.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 630 patients. To obtain
                          usable data, up to 30% more patients may need
                          to be enrolled.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: The length of
                          time needed to complete a medical history,
                          blood draw, and questionnaire regarding the
                          patient's age, race, and ethnicity.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 828/630 010724.
PROTOCOL DETAILS          STUDY DURATION: 24 months for sample
                          collection, 6 months for data analysis, 6 m
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 43
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (990616)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Seronegativity.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1009
PROTOCOL DETAILS          STUDY DESIGN: Cross-Sectional Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Signed informed consent of parent or
                          legal guardian for patients under 18.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed:
                          Decongestants, antihistamines, cough syrup,
                          vitamins, and nutritional supplements.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 01 days
                          less than or equal to 18 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Exposure to HIV in the prenatal period. 2.
                          History of clinically significant diseases or
                          findings that, in the investigator's opinion,
                          would compromise the outcome of this study.
                          (Significant diseases include diabetes
                          mellitus, asthma, rheumatoid arthritis, and
                          cystic fibrosis.).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Prescription
                          medications other than vitamins.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. HIV
                          infection. 2. Acute infectious illness. 3.
                          Chronic viral infection/disease. 4. Prior
                          enrollment on this study.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] No longer
                          recruiting 010227.
ALABAMA                   Univ of South Alabama 1504 Springhill Avenue
                          Mobile, AL 36604 Julie Bebawy [phone]
                          Recruiting 990913.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 991118.
CALIFORNIA                Cedars Sinai / UCLA Med Ctr 8700 Beverly
                          Boulevard Los Angeles, CA 900481804 Zane
                          O'Keefe [phone] No longer recruiting
                          010410.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] No longer recruiting
                          000912.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 990930.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          No longer recruiting 000817.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Susan Zamer
                          [phone] Recruiting 990908.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 991025.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 990930.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Deanna Cruz
                          [phone] Recruiting 010406.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          991202.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 000228.
ILLINOIS                  Mt Sinai Hosp Med Ctr / Dept of Pediatrics
                          Women's and Children's HIV Program / 15th
                          Street and CaliforniaChicago, IL 60608 Brenda
                          Wolfe [phone] Recruiting 000424.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 990730.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          991129.
LOUISIANA                 Tulane Univ Hosp of New Orleans 1430 Tulane
                          Ave New Orleans, LA 701122699 Kim Anglin
                          [phone] Recruiting 991014.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 990914.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 991227.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 990730.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 990930.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 990813.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone] No
                          longer recruiting 010702.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 000310.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Silvia Callejas
                          [phone] Recruiting 000419.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 000310.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 990903.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] Recruiting 991129.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 991129.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          991202.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 990927.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 991102.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] No longer recruiting
                          000727.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] No longer recruiting
                          001110.
NEW YORK                  Montefiore Med Ctr Adolescent AIDS Program
                          111 East 210th St Bronx, NY 10467 Dina Monte
                          [phone] No longer recruiting 000725.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          991124.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 990903.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 991025.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          991129.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone] No
                          longer recruiting 000817.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 990928.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 991025.

107
UNIQUE IDENTIFIER         NIH/01192
PROTOCOL ID NUMBERS       NIAID ACTG P1007
PROTOCOL TITLE            Multi-Drug Antiretroviral Therapy for Heavily
                          Pretreated Pediatric AIDS Patients: A Phase I
                          Proof of Concept Trial.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine the safety, tolerance,
                          pharmacokinetics, and antivirologic effect of
                          co-administering stavudine (d4T), didanosine
                          (ddI), lamivudine (3TC), nelfinavir (NFV),
                          ritonavir (RTV), saquinavir (SQV), and
                          nevirapine (NVP), at higher than standard
                          doses for selected drugs, with hydroxyurea
                          (HU) in pediatric AIDS patients with advanced
                          disease and prior therapy.
GENERAL DESCRIPTION       RATIONALE: Clinicians are increasingly
                          confronted with HIV-positive children who
                          have failed all available antiretroviral
                          therapies and have few viable treatment
                          options. Virologic failure in these patients
                          may be a result of antiretroviral resistance,
                          likely a result of poor adherence to the
                          treatment regimen or inadequate dosing. This
                          study is designed to achieve adherence
                          through observation of drug administration
                          for the first 8 weeks of the study and to
                          further overcome resistance by intensive,
                          high-dose, multi-drug therapy. Treatment with
                          more than four drugs has not been studied
                          formally in children, but pediatricians
                          caring for children with AIDS have used such
                          strategies off study with success. Dose
                          intensification may also aid in overcoming
                          resistance; therefore, in this trial, d4T,
                          3TC, and NFV are administered at up to twice
                          their standard doses. Given the limited
                          therapeutic options available to HIV-positive
                          children with poor prognoses, high-dose,
                          multi-drug therapy merits study. [AS PER
                          AMENDMENT 1/7/00: Pancreatitis, which may be
                          fatal in some cases, has occurred during
                          therapy with ddI. The risk of pancreatitis
                          may be increased when ddI is used in
                          combination with HU. ACTG A5025, a study that
                          had a d4T/ddI/HU arm, was terminated because
                          of significant toxicity concerns related to
                          the HU-containing arm. Patients enrolled in
                          ACTG P1007 may be at increased risk of
                          developing pancreatitis given their advanced
                          disease state and the use of multiple drugs
                          including HU. The study had been amended to
                          address these concerns.]
GENERAL DESCRIPTION       METHODOLOGY: Patient enrollment is staged to
                          allow study physicians to aggressively
                          monitor patients for signs of toxicity.
                          Initially, patients are admitted to a
                          hospital or clinical research center for 2
                          weeks, where they initiate an eight-drug
                          regimen and undergo frequent physical exams
                          and blood tests to assess pharmacokinetics,
                          virologic response, and toxicity. If
                          investigators identify important drug
                          interactions requiring modification of the
                          combination regimen, or if there are early
                          regimen-terminating toxicities, the trial
                          will be halted to address these concerns.
                          After 2 weeks, the patient is discharged to
                          return home. Study personnel visit the
                          patient's house twice a day for 6 more weeks
                          to observe drug administration, and the
                          patient continues to receive regular physical
                          exams and blood tests. At the end of Week 24,
                          all patients with plasma RNA levels of 10,000
                          copies/ml or less are offered the opportunity
                          to continue their regimen to Week 48.
                          Patients with plasma RNA levels above 10,000
                          copies/ml at Week 24 and patients who
                          experience virologic rebound at or after Week
                          24 are taken off study unless the patient's
                          family and the investigator feel it is in the
                          best interest of the child to remain on
                          study.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy,
                          Combination pharmacokinetics, Drug efficacy,
                          Drug safety, Drug tolerance, Drug toxicity.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 6 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks with
                          possible extension to 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1/6 991110.
PROTOCOL DETAILS          STUDY DURATION: 24 weeks with possible
                          extension to 48 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 19
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (000107)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG P1007
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Confirmed diagnosis of HIV infection
                          as defined by the Pediatric Virology Core
                          Laboratory Committee. 2. Pre-entry
                          immunologic Category 3 CD4+ T cell percent or
                          absolute count (less than 15 percent or less
                          than 200 cells/microL) within 30 days of
                          study entry. 3. Pre-entry RNA levels greater
                          than 100,000 copies/ml within 30 days of
                          study entry. 4. For patients under age 18,
                          parent or legal guardian's signed informed
                          consent. In those states where laws permit,
                          the child must know his/her HIV status and
                          provide assent to participate. 5. Motivation
                          and ability to conform to the complex
                          treatment regimen, as determined by the
                          care-site team and family.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 200 cells/microL or
                          <15%.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.9 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 9.9 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 59 Creatinine
                          clearance >= 59 cc/min/1.73 m2.
PATIENT INCLUSION CRIT.   OTHER: Less than Grade 2 fractionated amylase
                          and/or lipase. [AS PER AMENDMENT 1/7/00:
                          amylase and lipase <= 1.5 X ULN; fasting
                          triglyceride <= 1,000 mg/dl.].
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study Negative
                          pregnancy test.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: 1. RTV and NFV,
                          alone or in combination, for at least 6 weeks
                          prior to study entry. 2. Nucleoside reverse
                          transcriptase inhibitors (NRTIs) for more
                          than 6 months. 3. One or more nonnucleoside
                          reverse transcriptase inhibitors (NNRTIs) for
                          more than 6 months.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1. IVIG, as
                          monthly infusions and as a therapeutic
                          intervention. 2. Standard immunizations
                          except during the first 4 weeks of the study.
                          3. Colony stimulating factors (e.g.,
                          erythropoietin, G-CSF). 4. PCP prophylaxis
                          (use caution with dapsone). 5. Acute therapy
                          for intercurrent infections if the therapy is
                          not a disallowed medication. 6. Azithromycin
                          prophylaxis or treatment for Mycobacterium
                          avium intracellulare. 7. Megestrol acetate
                          and dronabinol (Megace and Marinol). 8.
                          Antifungal prophylaxis (use caution with
                          ketoconazole). 9. Antihyperlipidemic agents
                          (consult first with protocol chair). 10.
                          5-HT3 receptor antagonists. 11. Other
                          therapies for treatment of symptoms and
                          supportive care if not a disallowed
                          medication. Allowed with caution:
                          Atorvastatin, cerivastatin, dapsone,
                          ketoconazole, lovastatin, oral
                          contraceptives, quinolones, rifabutin,
                          rifampin, simvastatin, tetracyclines, other
                          medications interacting with RTV as outlined
                          in the protocol.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 07
                          years less than or equal to 21 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Excluded: 1.
                          History of clinical pancreatitis. Clinical
                          pancreatitis is defined as the symptomatic
                          presence of nausea, vomiting, or abdominal
                          pain associated with an elevation in
                          pancreatic amylase (fractionated amylase) or
                          lipase and/or pancreatic abnormalities on
                          imaging studies. 2. History of Grade 2 or
                          higher peripheral neuropathy. 3. History of
                          dose-limiting toxicity requiring treatment
                          discontinuation of any of the study
                          medications. 4. History of diabetes mellitus,
                          hepatitis C (confirmed by HCV PCR), hepatitis
                          B (confirmed by hepatitis B antigen
                          positivity), symptomatic cardiomyopathy, or
                          progressive encephalopathy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Acute treatment
                          for a serious bacterial, viral, or
                          opportunistic infection within 14 days prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          additional antiretrovirals, either
                          FDA-approved or investigational. 2. Any other
                          investigational agents. 3. Immunomodulatory
                          treatment with the exception of IVIG. 4.
                          Chemotherapy for malignancies. 5. Interacting
                          drugs as follows: alprazolam, amiodarone,
                          astemizole, bepridil, bupropion, cisapride,
                          clorazepate dipotassium, clozapine, diazepam,
                          dihydroergotamine, encainide, ergotamine and
                          ergot derivatives, estazolam, flecainide
                          acetate, flurazepam HCl, meperidine,
                          midazolam, pimozide, piroxicam, propafenone,
                          propoxyphene, quinidine, rifabutin, rifampin,
                          terfenadine, triazolam, zolpidem tartrate.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: 1. Known
                          hypersensitivity to the study medications. 2.
                          Any Grade 3 or higher lab abnormality other
                          than the specified laboratory findings listed
                          in Lab Values.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0164  Saquinavir
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 8  DRG-0253  Hydroxyurea
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 2 mg/kg bid. [AS PER
                          AMENDMENT 1/7/00: 1 mg/kg bid.] Drug 2: 240
                          mg/m2 qd. Drug 3: 8 mg/kg bid. Drug 4: 120
                          mg/m2 qd for 14 days, then 120 mg/m2 bid.
                          Drug 5: 60 mg/kg bid. Drug 6: 60-80 mg/kg
                          bid. Drug 7: 450 mg/m2 bid. Drug 8: 10-20
                          mg/kg qd
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Maximum daily dose: 160
                          mg. [AS PER AMENDMENT 1/7/00: 8Drug 2:
                          Maximum daily dose: 400 mg. Drug 3: Maximum
                          daily dose: 600 mg. Drug 4: Maximum daily
                          dose: 400 mg. Drug 5: Maximum daily dose:
                          2,400 mg. Drug 6: Maximum daily dose: 4,000
                          mg. Drug 7: Maximum daily dose: 2,400 mg.
                          Drug 8: Maximum daily dose: 1,000 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral or by gastric
                          tube. Drug 2: Oral or by gastric tube. Drug
                          3: Oral or by gastric tube. Drug 4: Oral or
                          by gastric tube. Drug 5: Oral or by gastric
                          tube. Drug 6: Oral or by gastric tube. Drug
                          7: Oral or by gastric tube (solution or
                          soft-gelatin capsuDrug 8: Oral or by gastric
                          tube
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks with possible
                          extension to 48 weeks.
OTHER TREATMENT INFO.     END POINT: Regimen-terminating toxicities,
                          adverse drug interactions, viral loads.
OTHER TREATMENT INFO.     DISCONTINUE: Study medications may be
                          discontinued for the following reasons: 1.
                          Toxicity. Grade 2 or 3 toxicities may result
                          in temporary or permanent discontinuation of
                          study drugs, as per protocol guidelines. For
                          Grade 4 toxicities, all study drugs are held.
                          Confirmation of Grade 4 endpoints results in
                          study termination unless otherwise stated in
                          the protocol. If two patients experience
                          regimen-terminating toxicities, the study is
                          halted and reassessed. [AS PER AMENDMENT
                          1/7/00: For Grade 1 pancreatitis, ddI and HU
                          are permanently discontinued. D4T is held and
                          may be permanently discontinued if symptoms
                          do not improve in the first 48 hours.] 2.
                          Intercurrent infection (consult with study
                          chair or co-chair). Note: Patients may
                          discontinue up to three antiretroviral agents
                          and still continue on study. Patients may
                          discontinue treatment for the following
                          reasons: 1. Viral load greater than 10,000
                          copies/ml at Week 24, unless the patient's
                          family and the investigator feel it is in the
                          best interest of the child to remain on
                          study. 2. Virologic rebound at or after Week
                          24, unless the patient's family and the
                          investigator feel it is in the best interest
                          of the child to remain on study. 3. Plasma
                          HIV RNA levels that have increased by 1 log
                          or more from baseline at any time, confirmed
                          by a second specimen. 4. Failure to adhere to
                          the study requirements so as to cause harm to
                          self or seriously interfere with the validity
                          of the study results. 5. Treatment required
                          with medications that necessitate
                          discontinuation of study medications. 6.
                          Pregnancy. 7. Refusal by the patient or legal
                          guardian to continue treatment and/or
                          follow-up evaluations. 8. Determination by
                          investigator that further participation would
                          be detrimental to the patient's health or
                          well-being.
OTHER TREATMENT INFO.     MODIFICATION: Dosage of study medications may
                          be modified as follows: When study medication
                          has been held and the investigator determines
                          the patient can resume the study
                          medication(s), as outlined in the protocol
                          guidelines for toxicity management, the
                          patient is re-started at a level-1 dose
                          reduction. For patients receiving reduced
                          dose(s) of study medication(s), dose
                          escalation to full dose should be considered
                          if signs, symptoms, or laboratory
                          abnormalities remain at an acceptable level
                          for more than 4 weeks, if approved by the
                          study chair or co-chair.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          990930.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Maryanne Dillon
                          [phone] Recruiting 010228.
FLORIDA                   Sacred Heart Children's Hosp / CMS of Florida
                          5192 Bayou Blvd Pensacola, FL 32503 Susan
                          Wilson [phone] Recruiting 001110.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 000515.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 010418.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000424.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 991208.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 991012.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 990913.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 001012.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 000726.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] Recruiting 990924.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 991129.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 000621.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 000726.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 990913.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          000726.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 991118.

108
UNIQUE IDENTIFIER         FDA/01189
PROTOCOL ID NUMBERS       FDA 303A
PROTOCOL TITLE            A Phase I/II, Open-Label Study of the Safety,
                          Tolerance, Pharmacokinetics, Drug-Interaction
                          and Anti-HIV Activity of Intramuscularly
                          Administered Alpha-Epi-Br (HE2000) in
                          HIV-Infected Patients on Salvage Therapy.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To evaluate: 1) the safety,
                          tolerability, and pharmacokinetics of HE2000
                          following single and repeated
                          administrations; 2) the potential for drug
                          interaction of HE2000 with other
                          antiretroviral agents; 3) the antiretroviral
                          activity of HE2000 and duration of viral
                          suppression following repeated
                          administrations; and 4) the potential for
                          drug-resistant virus as a result of an
                          intermittent dosing regimen.
GENERAL DESCRIPTION       RATIONALE: HE2000 is a synthetic steroid
                          hormone that, when tested in the laboratory,
                          had anti-viral activity against wild-type and
                          drug-resistant variants of HIV. HE2000 works
                          through a natural biochemical mechanism in
                          cells to make them less able to support viral
                          infection.
GENERAL DESCRIPTION       METHODOLOGY: There are 4 treatment groups of
                          increasing doses of HE2000; each group
                          consists of 2 parts (Part A and B). Part A is
                          a single administration of HE2000 injected
                          intramuscularly, and Part B is 5 consecutive
                          daily intramuscular injections of HE2000.
                          Patients receive the same dosage throughout
                          Parts A and B of the study. Patients are
                          asked to return to the clinic periodically
                          for blood sample collection. Patients may
                          remain at the hospital overnight for
                          pharmacokinetic evaluation. Drug safety,
                          tolerance, efficacy, and pharmacokinetics are
                          measured. Samples from treatment Group 4 are
                          analyzed for specific cell function.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010625)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug
                          interactions, Drug safety, Drug tolerance,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 42 patients. As of June
                          2001, enrollment for treatment Group 4 is
                          open in New York. 12 patients per treatment
                          Groups 1 through 3 and 6 patients in trea
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 6 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/42.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6
PROTOCOL DETAILS          VERSION NUMBER & DATE: (010104)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: HE2000-005
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Dose-Response
                          Design
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have/be: 1. HIV-1 infection determined by a
                          positive HIV antibody test confirmed by
                          Western blot, p24 antigen assay, HIV-1 RNA,
                          or HIV culture. 2. On current HAART regimen
                          for at least 30 days prior to the screening
                          visit. 3. Failing at least their second HAART
                          treatment. 4. Not responding to their current
                          antiretroviral therapy regimen, have failed
                          at least 1 HAART regimen, and have limited
                          treatment options (Groups 3 and 4 only). 5.
                          Willing to not make changes to his/her
                          antiretroviral treatment until at least Day
                          50 of the study. 6. CD4 count greater than or
                          equal to 100 cells/mm3 measured at the
                          screening and baseline visits. 7. Documented
                          stable HIV RNA titer between 5,000 and
                          250,000 copies/ml at the screening and
                          baseline visits.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 cells/microL.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl Or a creatinine
                          clearance > 70.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: WBC >= 1500 cells/microL.
                          Triglycerides <= 650 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Suppressive
                          or prophylactic therapy with aerosolized
                          pentamidine, trimethoprim/sulfamethoxazole,
                          dapsone, rifabutin, ketoconazole,
                          itraconazole, fluconazole, clarithromycin,
                          azithromycin, or acyclovir, if the patient
                          has been stable on the regimen for at least 4
                          weeks before enrollment. (Changes in such
                          treatment during the study are discouraged.).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Therapy that,
                          in the opinion of the investigator, would
                          make the patient unsuitable for the study or
                          unable to comply with the dosing
                          requirements.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks of
                          screening visit: 1. Systemic therapy for KS.
                          2. Anti-cancer chemotherapeutic agents.
                          Excluded within 14 days of screening visit:
                          Acute therapy for an active, serious
                          infection, including AIDS-defining
                          opportunistic infection.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          therapy for KS. 2. Therapy that, in the
                          opinion of the investigator, would make the
                          patient unsuitable for the study or unable to
                          comply with the dosing requirements. 3.
                          Immunomodulatory therapies including
                          interferon, interleukins, or steroids (i.e.,
                          testosterone, deca-durabolin, DHEA, and
                          oxandrolone). 4. Metabolic inhibitors (i.e.,
                          hydroxyurea, methotrexate, and
                          cyclophosphamide).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy other than cutaneous Kaposi's
                          sarcoma (KS) or basal cell carcinoma. (Note:
                          Patients with biopsy-confirmed KS are
                          eligible, but must not have received any
                          systemic therapy for KS within 4 weeks prior
                          to the screening visit and are not
                          anticipated to require systemic therapy
                          during the study.) 2. Active, serious
                          infection, including AIDS-defining
                          opportunistic infection requiring active or
                          maintenance treatment. 3. A clinical
                          condition that, in the opinion of the
                          investigator, would make the patient
                          unsuitable for the study or unable to comply
                          with the dosing requirements. 4. Co-infection
                          with hepatitis B or C virus. 5.
                          Glucose-6-phosphate dehydrogenase (G6PDH)
                          enzyme deficiency (hemoglobin less than or
                          equal to 6.0 g/dl).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0318  HE2000
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 25 mg, 50 mg, or 100
                          mg given as a single administratioas 5
                          consecutive daily injections
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intramuscular
                          injection
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 days total.
SUPPORTING AGENCY         Hollis-Eden Pharmaceuticals Inc.
LAST REVISION DATE        20010625
CALIFORNIA                Quest Clinical Research 2300 Sutter St San
                          Francisco, CA 94115 Eileen Glutzer
                          [phone] No longer recruiting As of June
                          1999 Group 1 (25 mg) is open fo enrollment.
                          010625.
CALIFORNIA                Veterans Affairs Palo Alto Health Care Ctr
                          AIDS Research Ctr / 3801 Miranda Ave Palo
                          Alto , CA 94304 Mark Mistal [phone] No
                          longer recruiting As of June 1999 Group 1 (25
                          mg) is open fo enrollment. 010625.
CALIFORNIA                ViRx Inc 1401 North Palm Canyon Dr / Suite
                          202 Palm Springs, CA 92262 Barbour Clayton
                          [phone] No longer recruiting 000807.
ILLINOIS                  Northwestern Univ Med School 303 East
                          Superior St / Passavant Pavilion Chicago, IL
                          60611 Jon Stanford [phone] No longer
                          recruiting As of June 1999 Group 1 (25 mg) is
                          open fo enrollment. 010625.
NEW YORK                  St Vincents Hosp / Clinical Research Program
                          36 7th Ave / Suite 415 New York, NY 10011
                          Margaret Granville [phone] Recruiting
                          Enrollment for only Group 4 is open. 010625.
TEXAS                     Plaza Med Ctr 1200 Binz St Houston, TX 77004
                          Dorothy Bartley [phone] No longer
                          recruiting As of June 1999 Group 1 (25 mg) is
                          open fo enrollment. 010625.

109
UNIQUE IDENTIFIER         NIH/01186
PROTOCOL ID NUMBERS       NIAID ACTG 736
PROTOCOL TITLE            Cerebrospinal Fluid Human Immunodeficiency
                          Virus-1 (HIV-1) and Cognitive Function in
                          Individuals Receiving Potent Antiretroviral
                          Therapy.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To compare the magnitude and
                          durability of suppression of HIV-1 RNA in the
                          plasma and cerebrospinal fluid (CSF)
                          compartments in response to potent
                          antiretroviral therapy. To determine if the
                          magnitude and durability of the CSF HIV-1 RNA
                          response to potent antiretroviral therapy is
                          associated with improved performance on
                          neuropsychological tests.
GENERAL DESCRIPTION       RATIONALE: HIV-1 RNA emerges in CSF early in
                          the course of HIV disease. Studies have shown
                          that high levels of HIV-1 RNA in CSF
                          correlate with increased severity of dementia
                          and worsened performance on
                          neuropsychological tests. While combination
                          antiretroviral treatments are potent
                          suppressors of HIV-1 replication in plasma,
                          the extent to which these treatments suppress
                          viral replication in CSF is unknown. A few
                          studies suggest that antiretroviral
                          treatments can reduce HIV-1 RNA in CSF.
                          However, since CSF is isolated from
                          peripheral immune responses to HIV and
                          antiretroviral treatment may not readily
                          penetrate the compartment, researchers
                          hypothesize the remaining virus will overcome
                          the antiretroviral treatment to achieve high
                          levels of viral replication again. This
                          virologic failure is likely accompanied by
                          decreased cognitive function. It is therefore
                          critical to determine the ability of
                          antiretroviral treatments to control HIV-1
                          replication in the CSF and the durability of
                          that viral suppression.
GENERAL DESCRIPTION       METHODOLOGY: Patients enrolling in 1 of
                          several AACTG-sponsored potent antiretroviral
                          therapy trials (a parent trial) may enter
                          this study. [AS PER AMENDMENT 6/6/00:
                          Patients already enrolled in an
                          AACTG-sponsored study who are changing
                          treatment due to virologic failure may also
                          enter this study.] Patients receive no
                          treatment but undergo various procedures
                          aimed at characterizing the effects of
                          antiretroviral therapies on CSF viral load
                          and cognitive function. Procedures include:
                          1) venipuncture to measure plasma HIV-1 RNA
                          and DNA levels, CD4+ T cell count, and
                          cytokine and immune activation markers
                          associated with HIV-1 neurological disorders;
                          2) neuropsychological examinations to measure
                          cognitive function; and 3) lumbar punctures
                          to obtain CSF samples, which are used to
                          determine the pharmacokinetics of
                          antiretroviral agents in CSF and to determine
                          levels of blood cells, cytokine and immune
                          activation markers, and HIV-1 RNA and DNA. An
                          entry visit must occur before initiating
                          potent antiretroviral therapy in the parent
                          trial [AS PER AMENDMENT 6/6/00: or before
                          changing the antiretroviral regimen due to
                          virologic failure in an ongoing trial].
                          Subsequent visits occur at 24 weeks, 12
                          months, and then annually. If evaluations,
                          procedures, or assays for a given patient's
                          parent trial occur at the times specified in
                          this study, they are not duplicated for this
                          study. Other visits may occur when a patient
                          changes antiretroviral treatment or
                          discontinues a parent trial.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Natural history.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients. Additional
                          patients may be coenrolled as part of ACTG
                          A5001. [AS PER AMENDMENT 6/6/00: A minimum of
                          100 patients will be enrolled into AC
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 24
                          weeks and up to several years, dependent on
                          the patient's continued participation in an
                          AACTG-sponsored potent antiretroviral therapy
                          trial.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 12/100 010724.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 24
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (000606)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AACTG 736
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Longitudinal
                          Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have CD4+ T cell count less than 200
                          cells/mm3 and plasma HIV-1 RNA above 2,000
                          copies/ml or plasma HIV-1 RNA levels greater
                          than 50,000 copies/ml and any CD4+ T cell
                          count. 2. Intend to enroll in an
                          AACTG-sponsored potent antiretroviral therapy
                          trial [AS PER AMENDMENT 6/6/00: or already be
                          enrolled in an AACTG-sponsored study but are
                          changing treatment due to virologic failure].
                          The screening and entry visits for ACTG 736
                          must occur before the initiation of
                          antiretroviral therapy [AS PER AMENDMENT
                          6/6/00: or before changing treatment because
                          of virologic failure].
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 200 cells/mm3 with
                          viral load > 2,000 copies/ml or any CD4+ T
                          cell count with viral load > 50,000
                          copies/ml.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: Prior
                          antiretroviral therapy.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Potent
                          antiretroviral therapy in an AACTG-sponsored
                          potent antiretroviral therapy trial. The
                          screening and entry visits for ACTG 736 must
                          occur before the initiation of antiretroviral
                          therapy [AS PER AMENDMENT 6/6/00: or before
                          changing treatment because of virologic
                          failure]. Allowed: 1. Treatment with aspirin
                          or nonsteroidal anti-inflammatory agents. 2.
                          Maintenance or prophylactic therapy for
                          opportunistic infections.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active drug or
                          alcohol abuse that, in the investigator's
                          opinion, could prevent compliance with study
                          procedures or confound the analysis of study
                          endpoints.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Completion of
                          treatment for any intercurrent acute
                          infection within 4 weeks of study entry.
                          Maintenance or prophylactic therapy is
                          allowed for opportunistic infections.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Treatment
                          with anticoagulants, including heparin, low
                          molecular weight heparin, warfarin, or
                          thrombolytics.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Any
                          active psychiatric illness including
                          schizophrenia, severe depression, and severe
                          bipolar affective disorder that, in the
                          opinion of the investigator, could confound
                          the analysis of the neurological examination
                          or neuropsychological test results. 2. Active
                          brain infection (except for HIV-1), brain
                          neoplasm, space-occupying brain lesion
                          requiring acute or chronic therapy. 3. Any
                          fungal meningitis, toxoplasmosis, or CNS
                          lymphoma. 4. Any contraindication to lumbar
                          puncture. Note: Pregnancy is allowed if the
                          parent study also allows pregnancy, except in
                          cases where neurological examination
                          indicates the need for a CT scan.
OTHER TREATMENT INFO.     END POINT: Virus not detectable in plasma and
                          CSF at Week 24 visit; changes in plasma and
                          CSF virus or in neuropsychological test
                          scores from entry to the Week 24 visit.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue the study
                          for the following reasons: 1. Patient changes
                          antiretroviral regimen because of an adverse
                          event. 2. Patient's potent antiretroviral
                          therapy trial is discontinued and the patient
                          does not enroll in another AACTG-sponsored
                          potent antiretroviral therapy trial. 3.
                          Patient becomes pregnant and requires a
                          computed tomography (CT) scan prior to lumbar
                          puncture. 4. Patient does not wish to
                          continue with the parent study or ACTG 736.
                          5. Study physician decides for any reason to
                          remove the patient from the study, including
                          failure by the patient to adhere to the study
                          requirements.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of California / San Diego Treatment Ctr
                          2760 5th Ave / Suite 300 San Diego, CA
                          921036325 Jill Kunkel [phone]
                          Recruiting 991209.
CALIFORNIA                Stanford Univ Med Ctr 300 Pasteur Dr / S-156
                          Stanford, CA 943055107 Debbie Slamowitz
                          [phone] Recruiting 001219.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          990707.
CALIFORNIA                San Mateo AIDS Program / Stanford Univ 300
                          Pasteur Drive / Room S-156 Stanford, CA
                          943055107 Debbie Slamowitz [phone]
                          Recruiting 001219.
CALIFORNIA                Willow Clinic 795 Willow Rd Menlo Park, CA
                          94025 Debbie Slamowitz [phone]
                          Recruiting 001219.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000419.
ILLINOIS                  Northwestern Univ Med School 676 N St Clair /
                          Suite 200 Chicago, IL 60611 Baiba L Berzins
                          [phone] Recruiting 000228.
MARYLAND                  Johns Hopkins Hosp 1830 East Monument St /
                          Room 8074 Baltimore, MD 21287 Rebecca Becker
                          [phone] Recruiting 010723.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 990809.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 001012.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] Recruiting 000629.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 991109.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 991208.
OHIO                      Univ of Cincinnati Eden and Albert Sabin Way
                          Cincinnati, OH 452670405 Tammy Powell
                          [phone] No longer recruiting 010115.
OHIO                      Ohio State Univ Hosp Clinic 456 West 10th Ave
                          / Room 4725 Columbus, OH 432101228 Judith
                          Neidig [phone] No longer recruiting
                          010213.
OHIO                      MetroHealth Med Ctr 2500 MetroHealth Dr
                          Cleveland, OH 441091998 Richard McVey
                          [phone] Recruiting 000824.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 001006.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          Recruiting 991208.
PENNSYLVANIA              Univ of Pittsburgh 7th Floor Falk Clinic /
                          200 Lothrop Street Pittsburgh, PA 15213
                          Christine Tripoli [phone] No longer
                          recruiting 010522.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000419.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 001024.
SOUTH CAROLINA            Julio Arroyo 206 Medical Circle / Suite 2A
                          West Columbia, SC 29169 Michael Klebert
                          [phone] Recruiting 990830.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd Dallas, TX 75390 Charla
                          Andrews [phone] Recruiting 010118.
WASHINGTON                Univ of Washington Harborview Med Ctr / 325
                          9th Ave Box 359929 Seattle, WA 98104 Jeanne
                          Conley [phone] Recruiting 991026.

110
UNIQUE IDENTIFIER         NIH/01179
PROTOCOL ID NUMBERS       NIAID CPCRA 061
PROTOCOL TITLE            Metabolic Consequences of Highly Active
                          Antiretroviral Therapy (HAART) in
                          HIV-Positive Individuals.
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Subha Raghavan
GENERAL DESCRIPTION       PURPOSE: The purpose of this study is to
                          compare the randomized HAART strategy groups
                          in the FIRST (Flexible Initial Retrovirus
                          Suppressive Therapies) protocol (CPCRA 058)
                          for changes in total cholesterol,
                          triglycerides, waist circumference, and
                          waist-to-hip ratio. The randomized HAART
                          strategies in the FIRST study are (1) a
                          protease inhibitor (PI)-containing regimen,
                          (2) a nonnucleoside reverse transcriptase
                          (NNRTI)-containing regimen, and (3) a
                          combination PI- and NNRTI-containing regimen.
                          Background nucleoside reverse transcriptase
                          inhibitor (NRTI) therapy is included in each
                          regimen.
GENERAL DESCRIPTION       RATIONALE: Close to 3 years into widespread
                          PI use, several toxicities, including
                          metabolic alterations, are being reported
                          increasingly in conjunction with the use of
                          PI-containing regimens. Some of the
                          manifestations of these metabolic alterations
                          include hyper/dyslipidemia, hyperglycemia,
                          insulin resistance and glucose intolerance,
                          lipodystrophy (in face and extremities), and
                          body fat redistribution (e.g., central
                          obesity and buffalo humps). Despite reports
                          of increasing prevalence of metabolic
                          complications among PI users, the question of
                          whether they result from PI therapy has not
                          been answered. Some of these complications,
                          e.g., a decrease in peripheral fat with an
                          increase in visceral fat and buffalo hump,
                          have been observed in HIV-infected
                          individuals who were not receiving PIs. This
                          study compares 3 different antiretroviral
                          regimens used in the FIRST study (CPCRA 058),
                          1 of which does not contain a PI, and
                          examines metabolic alterations which occur.
GENERAL DESCRIPTION       METHODOLOGY: This study enrolls patients
                          simultaneously co-enrolling in the FIRST
                          protocol; 120 patients from each of the FIRST
                          study strategy groups. At entry, Months 1 and
                          4, and then every 4 months, blood is drawn to
                          measure serum glucose, insulin, total
                          cholesterol, HDL cholesterol, LDL
                          cholesterol, and triglyceride levels. At
                          entry and Months 4, 8, 12, and then every 12
                          months, body cell mass, and body fat by
                          bioelectrical impedance analysis (BIA) are
                          assessed. [AS PER AMENDMENT 7/5/01: At Months
                          4, 8, and 12, then every 4 months through
                          closure of the FIRST protocol] patients are
                          weighed and skinfold measurements and body
                          circumference measurements are done.
                          Statistical evaluations are performed on the
                          data.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Clinical Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 460 patients. At least 120
                          in each of the FIRST study strategy groups.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 1 year
                          and up to 5 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 405/460 010731.
PROTOCOL DETAILS          STUDY DURATION: 7 to 8 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 15
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010705)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Cohort Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Written informed consent of parent
                          or guardian if under 18 years of age. 2.
                          Simultaneous co-enrollment in the FIRST study
                          (CPCRA 058).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
OTHER TREATMENT INFO.     END POINT: Changes in total cholesterol,
                          triglycerides, waist circumference, and
                          waist-to-hip ratio from baseline to 1 year
                          post randomization in the FIRST protocol.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Community Consortium / UCSF 3180 18th St /
                          Suite 201 San Francisco, CA 94110 Carroll
                          Child [phone] Recruiting 990804.
COLORADO                  Denver CPCRA / Denver Public Hlth 605 Bannock
                          St Denver, CO 802044507 Jack Rouff
                          [phone] Recruiting 990804.
DISTRICT OF COLUMBIA      Washington Reg AIDS Prog / Dept of Infect Dis
                          VA Med Ctr / 50 Irving St NW Washington, DC
                          20422 Barbara Standridge [phone]
                          Recruiting 990804.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon Ave / Suite 130 Atlanta, GA 303081962
                          Melanie Thompson MD [phone] No longer
                          recruiting 010528.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd #108 Chicago, IL 60657 Rita
                          Verheggen [phone] Recruiting 990804.
LOUISIANA                 Louisiana Comm AIDS Rsch Prog / Tulane Univ
                          Med 1430 Tulane Ave / TB 21 New Orleans, LA
                          70112 Janice Walker [phone] Recruiting
                          990804.
MICHIGAN                  Henry Ford Hosp 2799 West Grand Blvd /
                          CFP-104 Detroit, MI 48202 Diane Mastro-Polak
                          [phone] Recruiting 990804.
MICHIGAN                  Wayne State Univ - WSU/DMC / Univ Hlth Ctr
                          4201 Saint Antoine / POD 7C Detroit, MI 48201
                          Jan Kosmyna [phone] Recruiting 990804.
NEW JERSEY                Southern New Jersey AIDS Cln Trials / Dept of
                          Med 3 Cooper Plaza / Suite 220 Camden, NJ
                          08103 Maryann LiVolsi [phone]
                          Recruiting 990804.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Robert C Sawyer [phone]
                          Recruiting 990804.
NEW MEXICO                Partners in Research / New Mexico 915 Camino
                          de Salud NE Albuquerque, NM 87131 Cynthia
                          Nicholson [phone] Recruiting 990804.
NEW YORK                  Harlem AIDS Treatment Grp / Harlem Hosp Ctr
                          506 Lenox Ave / Rm 3101A New York, NY 10037
                          Luis Fuentes [phone] Recruiting 990804.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn St Portland, OR 97210 Norma Martinez
                          [phone] Recruiting Includes Vancouver
                          Canada area. 990804.
PENNSYLVANIA              Philadelphia FIGHT 1233 Locust St / 5th Floor
                          Philadelphia, PA 19107 Jane Shull
                          [phone] Recruiting 990804.
VIRGINIA                  Richmond AIDS Consortium / Div of Infect
                          Diseases PO Box 980049 Richmond, VA 232980049
                          Vinnie Mitchell [phone] Recruiting
                          990804.

111
UNIQUE IDENTIFIER         FDA/01178
PROTOCOL ID NUMBERS       FDA 006
PROTOCOL TITLE            A Phase III Multicenter Randomized Study of
                          the Biological and Clinical Efficacy of
                          Subcutaneous Recombinant, Human Interleukin-2
                          in HIV-Infected Patients with Low CD4+ Counts
                          Under Active Antiretroviral Therapy
                          (SILCAAT).
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To compare patients receiving both
                          Chiron recombinant human interleukin-2 (IL-2)
                          and antiretroviral treatment with patients
                          receiving only antiretroviral treatment with
                          respect to time of first AIDS-defining event
                          on study or death. Methodology: Patients are
                          randomized to 1 of 2 treatment arms. Patients
                          in Arm 1 receive subcutaneous IL-2 twice a
                          day for 5 days, every 8 weeks, in addition to
                          antiretroviral treatment. Patients in Arm 2
                          receive antiretroviral treatment only. In
                          both groups, CD4+ T cell counts and viral
                          load are monitored. Schedule of visits: All
                          patients (control group and IL-2 treated
                          group) have a medical examination and a blood
                          test every 2 months for the first year only,
                          and every 4 months thereafter for up to 6
                          years total.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to 1 of
                          2 treatment arms. Patients in Arm 1 receive
                          subcutaneous IL-2 twice a day for 5 days,
                          every 8 weeks, in addition to antiretroviral
                          treatment. Patients in Arm 2 receive
                          antiretroviral treatment only. In both
                          groups, CD4+ T cell counts and viral load are
                          monitored. Schedule of visits: All patients
                          (control group and IL-2 treated group) have a
                          medical examination and a blood test every 2
                          months for the first year only, and every 4
                          months thereafter for up to 6 years total.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open (010718)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 1400 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4 - 6 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 949/1400 010108.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 40
PROTOCOL DETAILS          VERSION NUMBER & DATE: (010109)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: CS-L2-9901. SILCAAT
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Randomized Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV-1 infection. 2. A
                          mean CD4 count of 2 points at least 50
                          cells/mm3 and less than 300 cells/mm3. 3. HIV
                          RNA levels must be below 10,000 copies/ml. 4.
                          Pregnancy is discouraged among IL-2
                          recipients, but if an IL-2 recipient wishes
                          to become pregnant after two years of trial
                          participation, she must alert the
                          investigator prior to interruption of
                          contraception.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.5 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 50 to 299 cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN ULN (Upper Limit of
                          Normal). Patients with Gilbert's syndrome or
                          protease inhibitor-induced hyperbilirubinemia
                          must have a serum bilirubin <= 5x ULN.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80 %.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test Negative pregnancy
                          test within 30 days of study entry.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Documented
                          antiretroviral treatment with at least 2
                          antiretroviral drugs for at least 4 months
                          prior to randomization, with no change in the
                          type of antiretroviral treatment received
                          during this 4-month period. For patients who
                          receive only 2 antiretrovirals, at least 1 of
                          these 2 medications should be a protease
                          inhibitor.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: Prescription
                          medications taken for HIV infection (e.g.,
                          antiretrovirals and prophylaxis for OIs).
                          Patients receiving IL-2 who are exposed to
                          iodinated contrast dye may experience an
                          acute onset of adverse reactions.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Any clinically significant medical condition.
                          2. Autoimmune disease with potentially
                          life-threatening complications. 3. Prior
                          participation in an ongoing IL-2 trial such
                          as the ESPRIT trial or protocol
                          non-compliance in a previous IL-2 trial 4.
                          HTLV-1 infection. 5. Evidence of active acute
                          infection within 2 weeks of randomization.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Psychiatric or
                          cognitive disturbances or illnesses, or
                          recreational drug/alcohol use that, in the
                          opinion of the principal investigator, would
                          affect patient safety and/or compliance.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Prior medical
                          history of transplantation.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. IL-2. 2.
                          Concurrent use or use within 4 weeks prior to
                          randomization of systemic corticosteroid
                          therapy or any agent, licensed or
                          experimental, with known immunomodulatory
                          effects (use of erythropoietin and anabolic
                          steroids is allowed). Current use, or use
                          within 4 weeks of randomization of cytotoxic
                          agents or antimetabolites; current use or use
                          within 4 months of randomization of
                          hydroxyurea or intravenous immunoglobulin. 3.
                          Receipt of iodinated contrast dye within 4
                          weeks of study entry. 4. Systemic
                          chemotherapy for malignancy within 12 months
                          prior to randomization.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Treatment
                          with other cytokines (with the exception of
                          erythropoietin), systemic corticosteroids,
                          IVIG (intravenous immunoglobulin),
                          immunomodulatory therapy, cytotoxic agents,
                          or antimetabolites will not be permitted.
                          Exceptions will be carefully considered on a
                          case-by-case basis and must be discussed with
                          the medical monitor.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Prior
                          history of AIDS: Eligibility: patients with
                          no prior history of AIDS or patients with the
                          following conditions as specified per
                          protocol: Candidiasis, esophageal; cervical
                          cancer, invasive; cryptosporidiosis,
                          isosporiasis; Kaposi's sarcoma; lymphoma,
                          Burkitt's; lymphoma, immunoblastic; M.
                          kansasii; Mycobacterium tuberculosis;
                          Pneumocystis carinii pneumonia; pneumonia,
                          recurrent; salmonella septicemia;
                          toxoplasmosis of brain; wasting syndrome due
                          to HIV. Ineligibility: patients with all
                          other AIDS defining conditions as specified
                          per protocol: Candidiasis of bronchi,
                          trachea, or lungs; coccidioidomycosis,
                          disseminated or extrapulmonary;
                          cryptococcosis, extrapulmonary;
                          cytomegalovirus disease (other than liver,
                          spleen, or nodes); cytomegalovirus retinitis
                          (with loss of vision); encephalopathy,
                          HIV-related; Herpes simplex: chronic ulcer
                          (greater than 1 month duration) or
                          bronchitis, pneumonitis, or esophagitis;
                          histoplasmosis, disseminated or
                          extrapulmonary; lymphoma, primary of brain;
                          Mycobacterium avium complex or disseminated
                          or extra pulmonary; Mycobacterium, other
                          species or unidentified species, disseminated
                          or extrapulmonary; progressive multifocal
                          leukoencephalopathy; American trypanosomiasis
                          (Chagas' disease) of the central nervous
                          system.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 4.5 MIU bid for 5
                          days every 8 weeks. Nonresponding patients
                          are allowed an increase to 6 MIU bid or MIU
                          bid contingent on tolerability. The increase
                          to the 7.5 MIUcan be incremental or immediate
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 - 6 years.
OTHER TREATMENT INFO.     END POINT: Time of first AIDS-defining event
                          on study, or death.
OTHER TREATMENT INFO.     DISCONTINUE: Patients will discontinue
                          treatment temporarily if any of the following
                          events occur: 1. Interruption of
                          contraception, pregnancy and breast-feeding.
                          2. Discontinuation of ART which will lead to
                          holding IL-2 for the same period of time.
                          Patients will discontinue treatment
                          permanently if any of the following events
                          occur: 1. Withdrawal of consent to actively
                          participate in the study. 2. The patient
                          experiences dose-limiting toxicities at the
                          minimal permissible dose (1.5 MIU twice a day
                          for 5 days every 8 weeks). 3. Malignancy
                          requiring systemic therapy. 4. Patient
                          non-compliance. 5. The principal investigator
                          believes it is in the best interest of the
                          patient.
SUPPORTING AGENCY         Chiron Corp.
LAST REVISION DATE        20010718
ALABAMA                   Univ of Alabama at Birmingham 908 S 20th St
                          Birmingham, AL 35294 Betty McCulloch
                          [phone] Recruiting 990910.
CALIFORNIA                San Francisco Gen Hosp / AIDS Division 995
                          Potrero Ave Bldg 80 San Francisco, CA 94110
                          Rosaleen Brennan [phone] Recruiting
                          991019.
CALIFORNIA                Saint Francis Mem Hosp 900 Hyde St San
                          Francisco, CA 94109 Lois Hillman
                          [phone] Recruiting 990910.
CALIFORNIA                Harbor UCLA Med Ctr 1124 West Carson St
                          Torrance, CA 90502 Petra Miller [phone]
                          Recruiting 990910.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Judy Carden
                          [phone] Recruiting 991021.
CALIFORNIA                Univ of Southern California SP21 Rand
                          Schrader Clinic / 1300 N Mission Rd Rm 349
                          Los Angeles, CA 90033 Irene Teran
                          [phone] Recruiting 000622.
CALIFORNIA                Santa Clara Valley Med Ctr 751 South Bascom
                          Ave San Jose, CA 95128 Arthi Chakravarthy
                          [phone] Recruiting 000905.
CALIFORNIA                Kaiser Foundation Hospital 4141 Geary Blvd /
                          Suite 219 San Francisco, CA 94118 Mary Beth
                          Charland [phone] Recruiting 990910.
CALIFORNIA                Orange Coast Med Group 361 Hosp Rd Suite 126
                          Newport Beach, CA 92663 Tony Navarro
                          [phone] Recruiting 990910.
CALIFORNIA                East Bay AIDS Ctr 2850 Telegraph Ave
                          Berkeley, CA 94705 Lucinda Hopewell
                          [phone] Recruiting 000905.
CONNECTICUT               Yale New Haven Hosp / Nathan Smith Clinic 15
                          York St New Haven, CT 06504 Cindy Frank
                          [phone] Recruiting 990910.
DISTRICT OF COLUMBIA      Georgetown Univ Med Ctr 3800 Reservoir Rd NW
                          / 110 Kober-Cogan Building Washington, DC
                          20007 Melanie Cordoro [phone]
                          Recruiting 991019.
DISTRICT OF COLUMBIA      Veterans Administration Med Ctr 50 Irving St
                          NW Washington, DC 20422 Charlotte Mauzy
                          [phone] Recruiting 990910.
FLORIDA                   Treasure Coast Infectious Disease Consultants
                          3715 7th Terrace Vero Beach, FL 32960 Jeff
                          Mieras [phone] Recruiting 000522.
FLORIDA                   Community AIDS Resource Inc 1320 South Dixie
                          Hwy Coral Gables, FL 33146 Christiane Jones
                          [phone] Recruiting 990910.
GEORGIA                   AIDS Research Consortium of Atlanta Inc 131
                          Ponce de Leon Ave Atlanta, GA 30308 Nicole
                          Miller [phone] Recruiting 990910.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd Chicago, IL 60657 Rita Verheggen
                          [phone] Recruiting 990910.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr /
                          Rush Med Coll 1653 West Congress Parkway 1577
                          Jelke Chicago, IL 60612 Danielle Merten
                          [phone] Recruiting 991019.
ILLINOIS                  Northwestern Univ Med School 303 E Superior
                          St Chicago, IL 60611 Ann McCord [phone]
                          Recruiting 990910.
INDIANA                   Indiana Univ Hosp 550 North Univ Blvd
                          Indianapolis, IN 462025250 Helen Romiger
                          [phone] Recruiting 001207.
MICHIGAN                  Henry Ford Hosp 2799 West Grand Blvd Detroit,
                          MI 48202 Linda Makohon [phone]
                          Recruiting 990910.
MISSOURI                  Washington Univ School of Med 5535 Delmar
                          Blvd St Louis, MO 63112 Mike Conklin
                          [phone] Recruiting 001021.
NORTH CAROLINA            Duke Univ Med Ctr / Infectious Disease Clinic
                          South Hosp Box 3306 / Trent Dr Durham, NC
                          27710 Meg McDaniel [phone] Recruiting
                          990910.
NORTH CAROLINA            Univ of North Carolina Burnett - Womack Bldg
                          / CB #7215 Chapel Hill, NC 275997215 Laurie
                          Frarey [phone] Recruiting 000920.
NEW MEXICO                Univ of New Mexico Health Science Center 2211
                          Lomas Blvd NE Albuquerque, NM 87131 Cynthia
                          Nicholson [phone] Recruiting 991019.
NEW YORK                  Howard A Grossman MD 155 West 19th St 4th
                          Floor New York, NY 10011 Howard A. Grossman
                          [phone] Recruiting 000522.
NEW YORK                  New York Univ Med Ctr 550 First Ave New York,
                          NY 10016 Richard Hutt [phone]
                          Recruiting 990910.
NEW YORK                  Liberty Medical 314 West 14th St / 4th Floor
                          New York, NY 10014 Debbie Goldman
                          [phone] Recruiting 001005.
NEW YORK                  Beth Israel Med Ctr 350 E 17th St New York,
                          NY 10003 Ann Marshak [phone] Recruiting
                          990910.
OHIO                      Ohio State Univ Med Ctr 456 West 10th Ave
                          Columbus, OH 43210 Judith Neidig
                          [phone] Recruiting 991019.
OHIO                      Univ Hosps of Cleveland 2061 Cornell Rd /
                          Foley Building Cleveland, OH 44106 Ann Conrad
                          [phone] Recruiting 990910.
OKLAHOMA                  Associates in Med and Mental Health 2325
                          South Harvard / Suite 600 Tulsa, OK 74114
                          Sheila Stafford [phone] Recruiting
                          990910.
PENNSYLVANIA              Bornemann Internal Medicine 145 N 6th Street
                          / Suite 205 Reading , PA 19601 Paula Shivers
                          [phone] Recruiting 000718.
PENNSYLVANIA              Hershey Med Ctr 500 Univ Dr Hershey, PA 17033
                          Kathleen Hay [phone] Recruiting 990910.
PENNSYLVANIA              Univ of Pittsburgh Med Ctr 200 Lothrop St
                          Pittsburgh, PA 15213 Nancy Mantz
                          [phone] Recruiting 990910.
TEXAS                     Univ of Texas / Med School at Houston 6431
                          Fannin Houston, TX 77030 Hilda Cuervo
                          [phone] Recruiting 990910.
TEXAS                     Univ of Texas Med Branch 301 University Blvd
                          Galveston, TX 77555 Cheryl Mogridge
                          [phone] Recruiting 990910.
TEXAS                     South Texas Veterans Health Care System 7400
                          Merton Minter Blvd San Antonio, TX 78284 Juan
                          Toro [phone] Recruiting 990910.
VIRGINIA                  Richmond AIDS Consortium 1001 East Broad St
                          Richmond, VA 23219 Patricia Dodson
                          [phone] Recruiting 990910.
WISCONSIN                 Univ of Wisconsin 600 Highland Ave #6/368
                          Madison, WI 53792 Shelly Beckwith
                          [phone] Recruiting 990910.

112
UNIQUE IDENTIFIER         FDA/01150
PROTOCOL ID NUMBERS       FDA 302A
PROTOCOL TITLE            Evaluation of the Safety and Antiviral
                          Efficacy of a Novel HIV-1 Protease Inhibitor,
                          BMS-232632, Alone and in Combination with d4T
                          and ddI as Compared to a Reference
                          Combination Regimen.
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To compare the antiviral activity of
                          3 doses levels of BMS-232632 with nelfinavir
                          (NFV) in combination with didanosine (ddI)
                          and stavudine (d4T) in antiretroviral naive
                          HIV-infected patients. Methodology: Patients
                          are randomized to receive one of two drug
                          regimens: BMS-232632, ddI, and d4T or NFV,
                          ddI, and d4T. Three different doses of
                          BMS-232632 are used in this study.
                          Randomization is stratified for HIV RNA level
                          (less than 30,000 copies/ml versus 30,000 or
                          greater copies/ml). Patients remain on their
                          drug regimen for 48 weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive one of two drug regimens: BMS-232632,
                          ddI, and d4T or NFV, ddI, and d4T. Three
                          different doses of BMS-232632 are used in
                          this study. Randomization is stratified for
                          HIV RNA level (less than 30,000 copies/ml
                          versus 30,000 or greater copies/ml). Patients
                          remain on their drug regimen for 48 weeks.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (000815)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 48
                          weeks.
PROTOCOL DETAILS          STUDY DURATION: At least 48 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 17
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: AI424-007
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Randomized
                          Control Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection. 2. HIV RNA viral
                          load between 2,000 and 200,000 copies/ml,
                          inclusive. 3. A CD4 cell count of at least
                          100 cells/mm3. 4. Availability for at least
                          48 weeks of follow-up.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   OTHER: Total serum lipase < 1.4 x ULN. GGT <
                          3 x ULN.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Intractable diarrhea within 30 days prior to
                          study entry. 2. History of acute or chronic
                          pancreatitis. 3. Acute hepatitis within 30
                          days prior to study entry. 4. History of
                          bilateral peripheral neuropathy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Any prior
                          antiretroviral therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. A
                          newly diagnosed HIV-related opportunistic
                          infection or condition requiring acute
                          therapy. 2. Suspected primary (acute) HIV
                          infection. 3. Hemophilia. 4. Inability to
                          tolerate oral medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0314  BMS-232632
RESULTS                   Squires K, Gatell J, Piliero P, Sanne I, Wood
                          R, Schnittman SM. 8th Conf Retro and Opportun
                          Infect. 2001 Feb 4-8 (abstract no. 15).
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
                          Drug 3: Oral Drug 4: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
SUPPORTING AGENCY         Bristol - Myers Squibb Pharmaceutical
                          Research Institute.
LAST REVISION DATE        20000815
ALABAMA                   Clinsites / Sorra Research Ctr 950 22nd St
                          North / Suite 550 Birmingham, AL 35203 Bonnie
                          Brewer [phone] Recruiting 990527.
ALABAMA                   Univ of Alabama at Birmingham 1917 Clinic /
                          908 South 20th St Birmingham, AL 35294 Wanda
                          Ball [phone] Recruiting 990527.
CALIFORNIA                UCSF - San Francisco Gen Hosp 635 Potrero Ave
                          San Francisco, CA 94110 Nelson Murcar
                          [phone] Recruiting 990527.
CALIFORNIA                UCSD Treatment Ctr 2760 5th Ave / Suite 300
                          San Diego, CA 92103 Francesca Torriani M.D.
                          [phone] Recruiting 990527.
COLORADO                  Univ of Colorado / Health Science Ctr 4200 E
                          Ninth Ave Denver, CO 80262 Graham Ray
                          [phone] Recruiting 990527.
DISTRICT OF COLUMBIA      ViRx / Dupont Circle Physicians Group 1737
                          20th St NW Washington, DC 20009 Linda Green
                          [phone] Recruiting 990527.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon Ave NE / Suite 130 Atlanta, GA 30308
                          Paul Couey [phone] Recruiting 990527.
ILLINOIS                  Rush Presbyterian - Saint Luke's Med Ctr 600
                          South Paulina St Chicago, IL 60612 Nancy
                          Hussa [phone] Recruiting 990527.
MISSOURI                  Washington Univ School of Medicine 4511
                          Forest Park / Suite 304 St Louis, MO 63108
                          Michael Klebert [phone] Recruiting
                          990527.
NEW YORK                  Beth Israel Med Ctr Division of Infectious
                          Diseases / 350 East 17th St New York, NY
                          10003 Ann Marshak [phone] Recruiting
                          990527.
NEW YORK                  Columbia Presbyterian Med Ctr Harkness
                          Pavilion 6 Room 644 / 622 West 168th Street
                          New York, NY 10032 Mykyelle Crawford
                          [phone] Recruiting 990527.
NEW YORK                  Albany Med College 47 New Scotland Ave / MC
                          142 Albany, NY 12208 Sandra Preston
                          [phone] Recruiting 990527.
OHIO                      Case Western Reserve Univ Foley Bldg / 2061
                          Cornell Rd Cleveland, OH 44106 Michael Chance
                          [phone] Recruiting 990527.
OTHER                     Ottawa General Hospital 501 Smyth Rd / Room
                          G12 Ottawa, ON Nanci Hawley-Foss
                          [phone] Recruiting 990527.
TEXAS                     Univ TX Galveston Med Branch 301 University
                          Blvd Galveston, TX 77555 Phyllis Galatas
                          [phone] Recruiting 990527.
TEXAS                     Oak Lawn Physicians Group 3514 Cedar Springs
                          Rd / Suite 200 Dallas, TX 75219 Joe Cheatum
                          [phone] Recruiting 990527.
TEXAS                     Univ of Texas Southwestern Med Ctr of Dallas
                          5323 Harry Hines Blvd / Building K1 900
                          Dallas, TX 75235 Sandra Tanksley
                          [phone] Recruiting 990527.

113
UNIQUE IDENTIFIER         NIH/01145
PROTOCOL ID NUMBERS       NIAID ACTG 371
PROTOCOL TITLE            A Trial to Evaluate the Safety and Efficacy
                          of Induction Treatment with Lamivudine Plus
                          Stavudine Plus Abacavir Plus
                          Amprenavir/Ritonavir Followed by Supervised
                          Treatment Interruption in Subjects with Acute
                          HIV Infection or Recent Seroconversion.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
PROTOCOL CHAIRS           CHAIR  Paul Volberding
GENERAL DESCRIPTION       PURPOSE: To assess if a potent antiretroviral
                          intervention early in the course of HIV
                          infection can lead to a decrease in plasma
                          HIV RNA to less than 200 copies/ml through 12
                          weeks following discontinuation of
                          maintenance therapy. [AS PER AMENDMENT
                          3/7/01: To compare between patients with
                          acute infection versus recent seroconversion
                          whether a potent antiretroviral intervention
                          early in the course of HIV infection can lead
                          to controlled viremia for 24 weeks off
                          treatment.] To evaluate the safety and
                          tolerance of the induction and maintenance
                          therapy arms when administered to patients
                          with acute HIV infection or recent
                          seroconversion.
GENERAL DESCRIPTION       RATIONALE: Acute, primary HIV infection
                          represents a potentially unique opportunity
                          to eradicate the infection. Although plasma
                          viral load rises rapidly, the dominant
                          infecting virus is relatively uniform
                          genetically, and infection may not be fully
                          established in all tissue sites until some
                          time after exposure. Current antiretroviral
                          therapy is able to reduce plasma viral load
                          to unmeasurable levels in established
                          infection. However, there are many questions
                          that remain about the treatment of primary
                          HIV infection. While it is assumed that
                          aggressive antiretroviral regimens are
                          required, it is not known how long they must
                          be continued. It is hoped that after an
                          interval of aggressive therapy, the number of
                          agents could be safely reduced. This study
                          evaluates if viral suppression can be
                          sustained after study therapy is withdrawn.
                          The drug regimen includes 2 relatively new,
                          potent antiretroviral drugs, amprenavir (a
                          protease inhibitor, or PI) and abacavir (a
                          nucleoside reverse transcriptase inhibitor,
                          or NRTI). [AS PER AMENDMENT 3/7/01: Recent
                          reports of the success of supervised
                          treatment interruption in patients who began
                          potent antiretroviral therapy early in their
                          infection are encouraging. However, these
                          studies have had only small numbers of
                          patients with limited duration of follow-up
                          and primarily included individuals treated
                          prior to seroconversion. This study proposes
                          to validate these preliminary data, as well
                          as to determine whether the benefits of early
                          treatment and supervised treatment
                          interruption extend into early infection
                          after seroconversion.]
GENERAL DESCRIPTION       METHODOLOGY: [AS PER AMENDMENT 3/7/01: The
                          new methods are as follows: Induction Phase
                          (Step 1): Patients receive open-label
                          treatment with lamivudine (3TC), stavudine
                          (d4T), abacavir (ABC), and amprenavir
                          (APV)/ritonavir (RTV) for at least 52 weeks.
                          Maintenance Phase (Step 2): Step 2 is closed
                          to enrollment with Version 3.0. Patients on
                          Version 2.0 are randomized to 1 of 3
                          treatment arms at Week 52. Patients in Arm A
                          continue induction therapy. Patients in Arm B
                          discontinue ABC. Patients in Arm C
                          discontinue APV/RTV. After Version 3.0 is
                          approved, patients may continue on the active
                          medications of their induction regimen and be
                          followed every 4 weeks per the Version 3.0
                          induction therapy schedule. Patients on
                          Version 3.0 who meet certain criteria for
                          treatment interruption proceed to Step 3.
                          Patients who entered the study prior to
                          Version 3.0 and choose not to undergo
                          treatment interruption or patients who are
                          ineligible for treatment interruption
                          continue on study medications through Week
                          112. Patients with confirmed HIV-1 RNA levels
                          of 5,000 copies/ml or greater after Week 16
                          should consider discontinuing study drugs and
                          should continue in study follow-up on an
                          alternative regimen at the discretion of
                          their physician. Treatment interruption (Step
                          3): All antiretroviral therapy is
                          discontinued simultaneously. Patients are
                          followed off therapy for 24 weeks or through
                          Week 112, whichever is later. Patients who
                          meet certain criteria for reinduction therapy
                          proceed to Step 4. Treatment is restarted for
                          patients who meet certain criteria.
                          Reinduction Phase (Step 4): Patients receive
                          treatment as in Step 1 minus ABC. Patients
                          who meet certain criteria for second
                          treatment interruption proceed to Step 5.
                          Patients who are ineligible for a second
                          treatment interruption continue on
                          reinduction therapy for 24 weeks or through
                          Week 112, whichever is later. Second
                          Treatment Interruption (Step 5): Treatment is
                          interrupted as in Step 3. Patients who meet
                          the criteria to restart therapy prior to Week
                          112 proceed to Step 6. Post-Interruption
                          Therapy (Step 6): Patients receive treatment
                          as in Step 4. Patients also may co-enroll in
                          immunologic, compartment, pharmacologic,
                          and/or medication compliance substudies.].
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 120 patients. A maximum of
                          120 patients [AS PER AMENDMENT 3/7/01: 60
                          patients] with recent HIV seroconversion.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: The duration of
                          the induction phase is 52 weeks. If a patient
                          has a plasma HIV RNA level below 200
                          copies/ml at Week 48, he/she is randomized at
                          Week 52 to the partially blinded maintenance
                          phase of the study and will receive 1 of 3
                          treatment st
PROTOCOL DETAILS          ACTUAL ACCRUAL: 41/120 010724.
PROTOCOL DETAILS          STUDY DURATION: 112 weeks. [AS PER AMENDMENT
                          3/7/01: A minimum of 112 weeks.].
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (010307)
PROTOCOL DETAILS          DISEASE STUDIED: HIV InfectionsS
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Random
                          Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Acute HIV infection or recent
                          seroconversion. Acute HIV infection is
                          defined as detectable plasma HIV RNA of 2,000
                          copies/ml or more by RT-PCR within 7 [AS PER
                          AMENDMENT 3/24/00: 14] days prior to study
                          entry and 1 of the following: (a) negative
                          ELISA within 7 [AS PER AMENDMENT 3/24/00: 14]
                          days of study entry; (b) positive ELISA but
                          negative or indeterminate Western blot within
                          7 [AS PER AMENDMENT 3/24/00: 14] days of
                          study entry; or (c) positive ELISA and
                          Western blot within 7 [AS PER AMENDMENT
                          3/24/00: 14] days of study entry but with
                          documented negative ELISA or plasma RT-PCR
                          (less than 2,000 copies/ml) within the 30
                          days prior to study entry. Recent HIV
                          seroconversion is defined as positive ELISA
                          and Western blot (more than 2 bands) within 7
                          [AS PER AMENDMENT 3/24/00: 14] days of study
                          entry but with documented negative ELISA or
                          plasma RT-PCR (less than 2,000 copies/ml)
                          within Days 31 to 90 prior to study entry [AS
                          PER AMENDMENT 3/24/00: or positive ELISA and
                          Western blot plus a nonreactive, less
                          sensitive (detuned) ELISA in patients with a
                          CD4+ cell count of 200/mm3 or greater, all
                          documented within 21 days (14 days or less
                          preferred) of study entry]. 2. Written
                          informed consent of parent or guardian if
                          under age 18.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.1 g/dl for men and >= 8.9
                          g/dl for women.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 /mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase <= 1.5 x ULN. Serum
                          lipase <= 1.5 x ULN. Triglycerides < 1200
                          mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study and for 90 days after Negative
                          pregnancy test.
PATIENT INCLUSION CRIT.   OTHER: This study is approved for prisoner
                          participation.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed prior to study
                          entry at the discretion of the protocol
                          chair/vice chair and protocol pharmacologist:
                          Alprazolam, amitriptyline, bupropion,
                          carbamazepine, chlorpheniramine,
                          chlorpromazine, chlorzoxazone, cimetidine,
                          clofibrate, clorazepate, clozapine, dapsone,
                          desipramine, diazepam, diltiazem, encainide,
                          erythromycin, estazolam, estrogens,
                          flecainide, fluconazole, flurazepam,
                          fluvastatin, glucocorticoids, imipramine,
                          isoniazid, itraconazole, ketoconazole,
                          labetalol, lamotrigine, lidocaine,
                          lovastatin, miconazole, morphine, naloxone,
                          nifedipine, nortriptyline, opioids, oxazepam,
                          phenobarbital, phenytoin, pimozide,
                          progesterones, promethazine, propafenone,
                          propofol, pr
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required for all
                          patients with CD4 cell count of 200 cells/mm3
                          or less: Chemoprophylaxis for Pneumocystis
                          carinii pneumonia. (Note: Concurrent use of
                          didanosine (ddI) and intravenous pentamidine
                          should be avoided.) Allowed: 1. Topical and
                          oral antifungal agents, except for oral
                          ketoconazole and itraconazole. 2. Treatment,
                          maintenance, or chemoprophylaxis with
                          approved agents for opportunistic infections
                          (except as noted). 3. Antibiotics (except as
                          noted). 4. Systemic corticosteroids for 21
                          days or less for acute problems. 5.
                          Recombinant erythropoietin, granulocyte
                          colony-stimulating factor, and
                          granulocyte-macrophage colony-stimulating
                          factor. 6. Regularly prescribed medications
                          such as antipyretics, analgesics, allergy
                          medications, antidepressants, sleep
                          medications, oral contraceptives, megestrol
                          acetate, or testosterone. 7. Alternative
                          therapies such as vitamins, acupuncture, and
                          visualization technique. 8. Sildenafil should
                          be given at the lowest dose, which is 25 mg
                          [AS PER AMENDMENT 3/24/00: 12.5 mg], when
                          continued on study. Allowed with the approval
                          of the protocol chair/vice chair and protocol
                          pharmacologist: Alprazolam, amitriptyline,
                          bupropion, carbamazepine, chlorpheniramine,
                          chlorpromazine, chlorzoxazone, cimetidine,
                          clofibrate, clorazepate, clozapine, dapsone,
                          desipramine, diazepam, diltiazem, encainide,
                          erythromycin, estazolam, estrogens,
                          flecainide, fluconazole, flurazepam,
                          fluvastatin, glucocorticoids, imipramine,
                          isoniazid, itraconazole, ketoconazole,
                          labetalol, lamotrigine, lidocaine,
                          lovastatin, miconazole, morphine, naloxone,
                          nifedipine, nortriptyline, opioids, oxazepam,
                          phenobarbital, phenytoin, pimozide,
                          progesterones, promethazine, propafenone,
                          propofol, propranolol, rifabutin,
                          simvastatin, T3, temazepam, valproic acid,
                          warfarin, [AS PER AMENDMENT 3/24/00:
                          allopurinol, disopyramide, fluoxetine,
                          hydroxyurea, mexiletine, nefazodone,
                          pentazocine, other beta blockers, rifabutin,
                          sildenafil,] or zolpidem.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 16
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1. A
                          history of acute or chronic pancreatitis
                          within 120 days prior to study entry. 2.
                          Documented or suspected acute hepatitis
                          within 30 days prior to study entry, even if
                          AST (SGOT) and ALT (SGPT) values are 5 x ULN
                          or less.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 30 days prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          antiretroviral therapy. [AS PER AMENDMENT
                          3/24/00: Prophylaxis completed more than 6
                          months prior to entry is allowed.] 2.
                          Cytotoxic chemotherapy within 30 days prior
                          to study entry. 3. HIV vaccination within 30
                          days prior to study entry, unless the study
                          chair makes an exception. 4. Any
                          investigational or experimental therapy
                          within 30 days prior to study entry [AS PER
                          AMENDMENT 3/24/00: with the exception of HIV
                          vaccination. Patients vaccinated for HIV
                          within 30 days prior to entry must have both
                          a positive HIV RNA and a positive ELISA]. 5.
                          Amiodarone, astemizole, bepridil, cisapride,
                          cholestyramine, ergot alkaloids or drugs
                          containing derivatives of ergot alkaloids,
                          ganciclovir, interferon-alfa, midazolam,
                          quinidine, ribavirin, rifampin, sucralfate,
                          terfenadine, [AS PER AMENDMENT 3/24/00:
                          flecainide, pimozide, propafenone, St. John's
                          wort,] or triazolam within 14 days prior to
                          study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Amiodarone, astemizole, bepridil, cisapride,
                          cholestyramine, ergot alkaloids or drugs
                          containing derivatives of ergot alkaloids,
                          ganciclovir, interferon-alfa, midazolam,
                          quinidine, ribavirin, rifampin, sucralfate,
                          terfenadine, [AS PER AMENDMENT 3/24/00:
                          flecainide, pimozide, propafenone, St. John's
                          wort,] or triazolam. 2. All antiretroviral
                          therapies other than study medications. 3.
                          Investigational drugs. 4. Systemic cytotoxic
                          chemotherapy. 5. Chronic systemic
                          corticosteroid use (more than 21 days). [6.
                          AS PER AMENDMENT 3/24/00: Drugs known to
                          cause pancreatitis. If such drugs are
                          required, ddI must be discontinued.] Avoided:
                          1. Herbal medications. 2. Concurrent use of
                          ddI and intravenous pentamidine. 3. Vitamin E
                          supplements for patients on APV. 4.
                          Grapefruits, grapefruit juice. 5. Medications
                          with hematologic toxicity or bone marrow
                          suppression.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded: Intercurrent
                          illness.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0258  Amprenavir
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 400 mg qd or 200 mg
                          bid. (250 mg qd or 125 mg bid if un60 kg.)
                          Drug 2: 40 mg bid. (30 mg bid if under 60
                          kg.) Drug 3: 150 mg bid. Drug 4: 300 mg bid.
                          Drug 5: 600 mg bid. Drug 6: 1,250 mg bid.
                          Drug 7: 100 mg bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: 400 mg. (250 mg if
                          under 60 kg.) Drug 2: 80 mg. (60 mg if under
                          60 kg.) Drug 3: 300 mg. Drug 4: 600 mg. Drug
                          5: 1,200 mg. Drug 6: 2,500 mg. Drug 7: 200 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral. Drug 5: Oral, 150
                          mg soft capsules. Drug 6: Oral. Drug 7: Oral,
                          100 mg soft gel capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 112 weeks. [AS PER
                          AMENDMENT 3/7/01: A minimum of 52 weeks.].
OTHER TREATMENT INFO.     END POINT: Efficacy: HIV RNA less than 200
                          copies/ml by the Roche Ultrasensitive assay
                          12 weeks after discontinuation of all
                          antiretroviral treatment (i.e., at Week 100),
                          without HIV RNA greater than or equal to 200
                          copies/ml at Weeks 2, 4, or 8 after
                          discontinuation. [AS PER AMENDMENT 3/7/01:
                          Efficacy endpoint: Viral load less than 5,000
                          copies/ml after 24 weeks of continuous
                          treatment interruption.] Safety: Cases with
                          signs and symptoms of Grade 2 and higher and
                          laboratory abnormalities of Grade 3 and
                          higher, other reported adverse experiences of
                          Grade 3 and higher, and all deaths regardless
                          of cause.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Ineligible for
                          Step 2 (Maintenance Phase) because viral load
                          is 2,000 copies/ml or higher. 2. Eligible for
                          Step 3 (Treatment Withdrawal [AS PER
                          AMENDMENT 3/7/01: Treatment Interruption). 3.
                          Reached [AS PER AMENDMENT 3/24/00: 12 weeks
                          beyond] primary study endpoint. 4.
                          Development of an exclusionary condition. 5.
                          Requirement for medications that are
                          disallowed while on this study. 6.
                          Drug-related toxicities. 7. Failure, without
                          reasonable cause, to attend 2 consecutive
                          clinic visits or to take study medications as
                          prescribed. 8. Death. 9. Pregnancy.
OTHER TREATMENT INFO.     MODIFICATION: Trial medication may be
                          interrupted at the discretion of the
                          investigator and according to the severity of
                          the adverse experience (AE). The doses of
                          ZDV, [AS PER AMENDMENT 3/24/00: ZDV is
                          deleted] ddI, and d4T may be reduced,
                          interrupted, or reintroduced according to
                          standard practice at the time, and depending
                          on the severity of the AE. Dose reductions
                          are not allowed for 3TC, ABC, APV, [AS PER
                          AMENDMENT 3/24/00: RTV,] or NFV.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
CALIFORNIA                Univ of California / San Diego Treatment Ctr
                          2760 5th Ave / Suite 300 San Diego, CA
                          921036325 Jill Kunkel [phone]
                          Recruiting 990629.
CALIFORNIA                Univ of Southern California / LA County USC
                          Med Ctr 5P21 Rand Schrader Clinic / 1300
                          North Mission Rd Los Angeles, CA 900331079
                          Luis Mendez [phone] Recruiting 990811.
CALIFORNIA                San Francisco Gen Hosp 995 Potrero Ave /
                          Building 80 / Ward 84 San Francisco, CA
                          941102859 Marc Gould [phone] Recruiting
                          990719.
CALIFORNIA                UCLA CARE Ctr 10833 Le Conte Ave / BH 412 -
                          CHS Los Angeles, CA 90095 Susan McCarthy
                          [phone] Recruiting 010405.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000829.
FLORIDA                   Univ of Miami School of Medicine 1800
                          Northwest 10th Ave / P O Box 016960 Miami, FL
                          331361013 Leslie Thompson [phone] No
                          longer recruiting 010402.
HAWAII                    Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp
                          / Young Building 5th Floor Honolulu, HI 96816
                          Debra Ogata-Arakaki [phone] Recruiting
                          990730.
MASSACHUSETTS             Harvard (Massachusetts Gen Hosp) 55 Fruit St
                          / Founders Bldg 8th Floor Boston, MA 02114
                          Teri Flynn [phone] Recruiting 990730.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave / ACTU C&D Bldg / Old Bellevue New
                          York, NY 10016 Maura Laverty [phone]
                          Recruiting 990623.
NEW YORK                  Columbia Presbyterian Med Ctr 180 Fort
                          Washington Ave / Harkness Pavilion New York,
                          NY 10032 Mykyelle Crawford [phone]
                          Recruiting 001012.
NEW YORK                  Mount Sinai Med Ctr One Gustave Levy Place /
                          PO Box 1042 New York, NY 10029 Eileen Chusid
                          [phone] No longer recruiting 010227.
NEW YORK                  Chelsea Ctr Cornell Univ Clinical Trials Unit
                          / 525 East 68th St New York, NY 10021 Brenda
                          Greenhill [phone] No longer recruiting
                          000502.
NEW YORK                  Beth Israel Med Ctr First Ave at 16th St / 19
                          Baird Hall New York, NY 10003 Ann Marshak
                          [phone] Recruiting 990812.
NEW YORK                  Univ of Rochester Medical Center 601 Elmwood
                          Ave Rochester, NY 14642 Carol Greisberger
                          [phone] Recruiting 990730.
NEW YORK                  Cornell Univ Med Ctr Cornell Univ Clinical
                          Trials Unit / 525 East 68th St / ACTG BoxNew
                          York, NY 10021 Brenda Greenhill [phone]
                          No longer recruiting 000502.
OTHER                     Univ of Puerto Rico PO Box 365067 San Juan,
                          PR 009365067 Virginia Ramirez [phone]
                          No longer recruiting 010501.
PENNSYLVANIA              Univ of Pennsylvania at Philadelphia 536
                          Johnson Pavilion / 3600 Hamilton Walk
                          Philadelphia, PA 19104 Christopher Helker
                          [phone] Recruiting 000210.
RHODE ISLAND              Miriam Hosp / Brown Univ 164 Summit Ave
                          Providence, RI 02906 Joan Gormley
                          [phone] Recruiting 001019.

114
UNIQUE IDENTIFIER         NIH/01142
PROTOCOL ID NUMBERS       NIAID ACTG 391
PROTOCOL TITLE            Use of a Live-Attenuated Varicella-Zoster
                          Virus (VZV) Vaccine to Boost Immunity to VZV
                          in HIV-Infected Children Previously Infected
                          with Varicella.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Vaccine
PROTOCOL CHAIRS           CHAIR  Anne Gershon
GENERAL DESCRIPTION       PURPOSE: To monitor short-term local and
                          systemic reactions following administration
                          of live-attenuated varicella-zoster virus
                          (VZV) vaccine in HIV-infected children with
                          previous varicella and no prior history of
                          herpes zoster (HZ).
GENERAL DESCRIPTION       RATIONALE: Varicella (chickenpox) results
                          from primary infection with VZV. Varicella, a
                          common and usually benign illness in normal
                          children, is more severe in HIV-infected
                          children and may result in other conditions
                          such as HZ (shingles). HZ is due to
                          reactivation of latent VZV acquired during
                          varicella and is common in HIV-infected
                          children who have had natural varicella.
                          While HZ is not likely to be life-threatening
                          in these children, it does cause considerable
                          morbidity and interferes with quality of
                          life. Use of a live-attenuated VZV vaccine
                          may be able to boost immunity in these
                          children.
GENERAL DESCRIPTION       METHODOLOGY: Two immunologic cohorts are
                          enrolled. Cohort A includes children with a
                          CD4 cell percentage greater than or equal to
                          20 percent that has been documented as stable
                          for at least the 6 months prior to the time
                          varicella developed (confirmed by a minimum
                          of 2 tests) and a CD4 cell percentage greater
                          than [AS PER AMENDMENT 10/27/99: or equal to]
                          15 percent that has been documented as stable
                          for at least the 6 months prior to enrollment
                          (confirmed by a minimum of 2 tests). Cohort B
                          includes children with a CD4 cell percentage
                          greater than or equal to 10 percent and less
                          than 15 percent that has been documented as
                          stable for at least the 6 months prior to the
                          time varicella developed and stable for at
                          least the 6 months prior to enrollment
                          (confirmed by a minimum of 2 tests). [AS PER
                          AMENDMENT 4/20/01: Cohort B includes children
                          who have a CD4 cell percentage less than 15%
                          documented by a minimum of 1 but preferably 2
                          tests within 1 year of onset of varicella
                          (i.e., within 1 year before to 1 year after
                          varicella) and a CD4 cell percentage greater
                          than or equal to 15% documented by a minimum
                          of 2 tests at the time of enrollment.] A
                          pilot study precedes the full study. [AS PER
                          AMENDMENT 10/27/99: The pilot study for
                          Cohort A precedes the full study for Cohort A
                          and the pilot study for Cohort B. The pilot
                          study for Cohort B precedes the full study
                          for Cohort B.] The pilot study includes 10
                          children from each cohort who receive
                          live-attenuated VZV at Weeks 0 and 8. If 3
                          pilot-study patients in a cohort meet a
                          toxicity endpoint related to the vaccine, the
                          dose regimen has failed the safety criteria
                          for that cohort. [AS PER AMENDMENT 10/27/99:
                          If 3 children in the pilot study for Cohort A
                          meet a toxicity endpoint deemed to be related
                          to the vaccine, the dose regimen has failed
                          safety criteria for both cohorts. If 3
                          children in the pilot phase of Cohort B meet
                          a toxicity endpoint deemed related to the
                          vaccine, the dose regimen has failed the
                          safety criteria for Cohort B.] If, at 12
                          weeks after immunization, at least 5
                          pilot-study patients in a cohort respond and
                          the safety profile is deemed adequate, the
                          pilot study extends into a full study with
                          the immunization of an additional 20 patients
                          from that cohort. [AS PER AMENDMENT 10/27/99:
                          If, at Week 12, at least 5 pilot-study
                          patients in Cohort A meet immunologic
                          criteria and the safety profile is deemed
                          adequate, then the full study for Cohort A
                          and the pilot study for Cohort B opens. If
                          the same immunologic and safety criteria are
                          met for the pilot study for Cohort B, then
                          the full study for Cohort B opens.] If either
                          cohort shows an inadequate immunologic
                          response or safety profile, the study team
                          reviews the results to determine if another
                          regimen should be considered. In the full
                          study, patients receive 2 immunizations, at
                          Weeks 0 and 8. Varicella antibody titers and
                          in vitro responder cell frequency (RCF)
                          assays are measured at Weeks 0, 4, 8, 12, 24,
                          52, 78, and 104. Symptoms, HIV progression,
                          and VZV presence are monitored throughout the
                          study.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Vaccine prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 to 60 patients. 10
                          children per cohort in pilot study plus an
                          additional 20 children per cohort in full
                          study.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 40/20 to 60 001108.
PROTOCOL DETAILS          STUDY DURATION: 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 57
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (010420)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 391
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: All patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV culture, HIV
                          antigen, plasma HIV-1 RNA PCR, or a second
                          antibody test by a method other than ELISA.
                          ELISA is not necessary if there are 2
                          positive virologic tests. [AS PER AMENDMENT
                          10/27/99: The following statement regarding
                          subjects with acute HIV infection is no
                          longer part of the eligibility criteria.]
                          Patients with acute HIV infection defined by
                          either 2 positive virologic tests (positive
                          viral culture, HIV antigen, or PCR) or 1
                          positive virologic test plus symptoms of
                          acute infection including fever,
                          lymphadenopathy, or seroconversion documented
                          by ELISA testing with negative ELISA followed
                          by positive ELISA within 3 months on
                          different specimens will be eligible to
                          participate regardless of results of ELISA
                          testing if other eligibility criteria are
                          met. 2. Positive VZV antibody titer (FAMA or
                          latex agglutination). [AS PER AMENDMENT
                          10/27/99: Latex agglutination is no longer
                          included. An ELISA test does not need to be
                          performed.] 3. History of varicella greater
                          than 6 months prior to study entry, and at 1
                          year of age or older. 4. Written informed
                          consent of parent or legal guardian. Patients
                          in Cohort A must have : CD4 cell percentage
                          greater than or equal to 20% documented as
                          stable for at least the 6 months prior to the
                          time varicella developed (confirmed by a
                          minimum of 2 tests) and CD4 greater than [AS
                          PER AMENDMENT 10/27/99: or equal to] 15%
                          documented as stable for at least the 6
                          months prior to enrollment (confirmed by a
                          minimum of 2 tests). Patients in Cohort B
                          must have: CD4 cell percentage greater than
                          or equal to 10% and less than 15% documented
                          as stable for at least the 6 months prior to
                          the time varicella developed and stable for
                          at least the 6 months prior to enrollment
                          (confirmed by a minimum of 2 tests each). [AS
                          PER AMENDMENT 4/20/01: CD4 cell percentage
                          less than 15% documented by a minimum of 1
                          but preferably 2 tests within 1 year of onset
                          of varicella (i.e., within 1 year before to 1
                          year after varicella) and a CD4 cell
                          percentage greater than or equal to 15%
                          documented by a minimum of 2 tests at the
                          time of enrollment. Note: One test may be
                          done at screening. The second test must be
                          done within the 6 months prior to
                          screening.].
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 cells/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: See Inclusion - General
                          Criteria.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.1 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant Negative pregnancy test.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Stable
                          antiretroviral therapy for at least 3 months.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required: Stable
                          antiretroviral therapy with no projected
                          change in therapy. [AS PER AMENDMENT
                          10/27/99: If a child's antiretroviral therapy
                          is modified after the first VZV immunization,
                          the study chair will determine, on a
                          case-by-case basis, if the second
                          immunization should be given.].
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 02
                          years less than or equal to 18 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Active intercurrent illness within 72 hours
                          of entry. 2. Fever over 101 F within 72 hours
                          of entry (rectal reading preferred). 3.
                          Chickenpox exposure and/or exposure to HZ
                          (shingles) within 4 weeks prior to entry. 4.
                          History of HZ. 5. HIV-infected, indeterminate
                          [AS PER AMENDMENT 10/27/99: unknown HIV
                          status], or other immunocompromised household
                          members who have no known history of
                          varicella infection. (Eligible siblings may
                          be enrolled, provided they are vaccinated at
                          the same time.) 6. Coenrollment in ACTG 265.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Blood products
                          within 1 year prior to a study immunization.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Blood
                          products within 1 year before or 2 months
                          after a study immunization.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any systemic
                          (oral or parenteral) steroids or any other
                          immunosuppressive therapy within 30 days of
                          study entry. 2. Receipt of a live vaccine
                          within 30 days prior to a study immunization.
                          3. Receipt of an inactivated vaccine within 2
                          weeks prior to a study immunization. 4. Any
                          anti-herpes virus drug (e.g., acyclovir,
                          famciclovir, valacyclovir, cidofovir,
                          ganciclovir, interferon, and foscarnet)
                          within 1 week before a study immunization. 5.
                          VZIG or IVIG within 1 year prior to a study
                          immunization. 6. Prior receipt of varicella
                          vaccine.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Live
                          vaccine within 30 days before or after a
                          study immunization. 2. Inactivated vaccine
                          within 2 weeks before or after a study
                          immunization. 3. Current use of aspirin or
                          expected use within 6 weeks after a study
                          immunization. 4. Anti-herpes antiviral drugs
                          (e.g., acyclovir, famciclovir, valacyclovir,
                          cidofovir, ganciclovir, interferon, and
                          foscarnet) within 1 week before or 3 weeks
                          after a study immunization. 5. Systemic
                          corticosteroid within 30 days after a study
                          immunization. 6. Treatment with VZIG or IVIG
                          within 1 year before or 2 months after a
                          study immunization.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Known hypersensitivity to vaccine components,
                          including neomycin. 2. Other chronic medical
                          or surgical conditions or contraindications
                          which, in the opinion of the investigator,
                          may interfere with the evaluation of protocol
                          objectives.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0248  Varicella Virus Vaccine
                          (Live)
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Immunization at
                          Weeks 0 and 8
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous injection
OTHER TREATMENT INFO.     TREATMENT DURATION: Immunization at Weeks 0
                          and 8.
OTHER TREATMENT INFO.     END POINT: Adverse reactions with a severity
                          of at least Grade 3 which cannot be directly
                          attributed to other causes; twofold increase
                          in VZV:RCF.
OTHER TREATMENT INFO.     DISCONTINUE: Patients will discontinue
                          treatment for the following reasons: 1. Any
                          Grade 4 toxicity. 2. Selected Grade 3
                          toxicities (for example, Grade 3 seizure or
                          allergic reaction). 3. Systemic/dermatologic
                          toxicity: Severe varicella-like illness (over
                          100 lesions, hemorrhagic lesions, pneumonia,
                          encephalitis). 4. Immunologic decline defined
                          as a decrease both in absolute CD4 cell
                          percentage of greater than 50 percent and of
                          at least 50 cells/mm3 compared with the CD4
                          cell count prior to immunization.
OTHER TREATMENT INFO.     MODIFICATION: Toxicities will be managed as
                          follows: 1. Unacceptable toxicities as per
                          protocol must be resolved before the next
                          dose of vaccine may be administered. [2. AS
                          PER AMENDMENT 10/27/99: If the toxicity rate
                          for the full-study phase for Cohort A is over
                          30 percent of the accrued children, the dose
                          regimen for the whole study is suspended. If
                          the toxicity rate for the full-study phase
                          for cohort B is over 30 percent of the
                          accrued children, the dose regimen for only
                          Cohort B is suspended. The protocol team will
                          review available data and take appropriate
                          action.].
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          000817.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 000817.
CALIFORNIA                Children's Hosp of Oakland 747 52nd St
                          Oakland, CA 946091809 Teresa Courville
                          [phone] Recruiting 000817.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 000817.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 000817.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 000817.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] Recruiting 000817.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Maryanne Dillon
                          [phone] Recruiting 000817.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 000817.
CONNECTICUT               Connecticut Children's Med Ctr 263 Farmington
                          Ave Farmington, CT 060303805 Gail Karas
                          [phone] Recruiting 001031.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] Recruiting 000817.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Susan Zamer
                          [phone] Recruiting 000817.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 000817.
FLORIDA                   Sacred Heart Children's Hosp / CMS of Florida
                          5192 Bayou Blvd Pensacola, FL 32503 Michelle
                          Zubon McAtee [phone] Recruiting 010316.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Brenda Haliburton-Jones [phone]
                          Recruiting 000817.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 000817.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          000817.
GEORGIA                   Med College of Georgia 1120 15th St / Dept of
                          Pediatrics / HF 1135 Augusta, GA 30912 Teresa
                          Horne [phone] Recruiting 010316.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 000817.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 000817.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          000817.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] Recruiting
                          000817.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 000817.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000817.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 000817.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 000817.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 000817.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 000817.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 000817.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 000817.
NEW JERSEY                Saint Joseph's Hosp and Med Ctr/UMDNJ - New
                          Jersey Med Schl 185 South Orange Ave Newark,
                          NJ 07103 Mary Jo Hoyt [phone]
                          Recruiting 000817.
NEW JERSEY                UMDNJ - Robert Wood Johnson Med School /
                          Pediatrics One Robert Wood Johnson Place New
                          Brunswick, NJ 089030019 Silvia Callejas
                          [phone] Recruiting 000817.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 000817.
NEW JERSEY                Cooper Hosp - Univ Med Ctr / UMDNJ - New
                          Jersey Med Schl One Cooper Plaza Camden, NJ
                          08103 Mary Jo Hoyt [phone] Recruiting
                          000817.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 000817.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Denise Swindell
                          [phone] No longer recruiting 010712.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 000817.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] Recruiting 000817.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 000817.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 000817.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          000817.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 000817.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 000817.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 000817.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 000817.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 000817.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          000817.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 000817.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          000817.
PENNSYLVANIA              Saint Christopher's Hosp for Children Erie
                          Ave at Front St Philadelphia, PA 191341095
                          Audrey Kamrin [phone] Recruiting
                          000817.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone]
                          Recruiting 000817.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          000817.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 000817.
VIRGINIA                  Children's Hosp of the King's Daughters 601
                          Children's Lane Norfolk, VA 23507 Donna
                          Sandifer [phone] Recruiting 010118.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 000817.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 000817.

115
UNIQUE IDENTIFIER         NIH/01120
PROTOCOL ID NUMBERS       CC 89 I-0035
PROTOCOL TITLE            Effects of Infection with the Human
                          Immunodeficiency Virus on the Development and
                          Function of Bone Marrow Cells.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To examine the effects of HIV
                          infection on the development and function of
                          bone marrow cells.
GENERAL DESCRIPTION       RATIONALE: Hematologic abnormalities occur
                          with high frequency in HIV-infected
                          individuals; however, the pathogenesis of
                          these abnormalities is not currently
                          understood. Understanding the pathogenesis of
                          abnormal hematopoiesis seen in HIV infection
                          will allow investigators to design
                          appropriate therapeutic strategies.
GENERAL DESCRIPTION       METHODOLOGY: Volunteers will donate bone
                          marrow cells. These cells will be used to
                          study how HIV affects blood cells.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must
                          be: 1. HIV seropositive or HIV seronegative.
                          2. Zairian patients who were studied by the
                          principal investigator on site in Zaire.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA ACCRUAL 990402.

116
UNIQUE IDENTIFIER         NIH/01119
PROTOCOL ID NUMBERS       NCI 83 C-0022
PROTOCOL TITLE            Psychological Benefits of a Normalized
                          Camping Experience for Children with Cancer
                          and HIV Infection.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
GENERAL DESCRIPTION       PURPOSE: To assess the psychological benefits
                          of a normalized camping exerience in
                          pediatric cancer and HIV patients.
                          Methodology: A one-week camping trip, to
                          provide a normalized camping experience,
                          will be followed by an assessment of benefits
                          to patients and staff.
GENERAL DESCRIPTION       METHODOLOGY: A one-week camping trip, to
                          provide a normalized camping experience,
                          will be followed by an assessment of benefits
                          to patients and staff.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: One week.
PROTOCOL DETAILS          STUDY DURATION: One week.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Survey
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Cancer (for which they are currently
                          being treated or for which they have received
                          treatment in the past 3 years) or HIV
                          infection.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Cancer treatment
                          within the past 3 years. Allowed: Blood
                          products.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed:
                          Intramuscular, intrathecal, oral, or
                          intravenous medications.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 03
                          years less than or equal to 17 years.
SUPPORTING AGENCY         Natl Cancer Institute.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA ACCRUAL 990402.

117
UNIQUE IDENTIFIER         NIH/01117
PROTOCOL ID NUMBERS       CC 96 I-0108
PROTOCOL TITLE            Fluconazole Prophylaxis of Thrush in AIDS.
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the use of intermittent
                          fluconazole prophylaxis in the prevention of
                          thrush (oropharyngeal candidiasis).
                          Methodology: Patients receive fluconazole
                          three times each week.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive fluconazole
                          three times each week.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: Candidiasis, Oral.
PROTOCOL DETAILS          STUDY DESIGN: Placebo-Controlled Trial
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Documented history
                          of CD4 cell count less than 150 cells/mm3. 3.
                          At least 1 episode of thrush in the past 6
                          months, but fewer than 3 episodes within the
                          last 3 months. 4. Ability to tolerate oral
                          medications. 5. Life expectancy of at least 6
                          months.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   CREATININE: < 3.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant No abstinence or no agreement to use
                          effective method of birth control /
                          contraception during the study.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of esophageal candidiasis. 2. History
                          of thrush unresponsive to 200 mg daily of
                          fluconazole or requiring more than 14 days of
                          treatment.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Breast-feeding
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study Pregnant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Continuous azole
                          treatment for the prevention of fungal
                          infections for 1 month or more within the
                          past 6 months.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Continuous antifungal therapy. 2. Azole
                          treatment for recent mucosal infection.
                          (Note: These patients can enroll 2 weeks
                          after completion of azole therapy.).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Allergy or intolerance to azoles. 2. Systemic
                          fungal infection requiring continuous
                          antifungal therapy. 3. Severe liver disease.
                          4. Active mucosal infection or symptoms of
                          OPC/EC at time of initial assessment. (Note:
                          Can enroll 2 weeks after resolution of the
                          active episode.) 5. Severe renal
                          insufficiency as indicated by a serum
                          creatinine greater than or equal to 3.0.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0005  Fluconazole
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA ACCRUAL 990524.

118
UNIQUE IDENTIFIER         NIH/01113
PROTOCOL ID NUMBERS       NIAID CPCRA 060
PROTOCOL TITLE            A Prospective Study of Long-Term Clinical,
                          Virologic, and Immunologic Outcomes in
                          HIV-Infected Individuals.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To compare rates, within individual
                          CPCRA clinical trials, of morbidity and
                          mortality in patients randomized to different
                          HIV treatment or management strategies: (1)
                          CPCRA 058, FIRST: To compare 3 strategies of
                          first-time HAART for delaying disease
                          progression and death. (2) CPCRA 059,
                          interleukin-2 (IL-2): To compare the effect
                          of subcutaneous IL-2 plus antiretroviral
                          therapy versus antiretroviral therapy alone
                          in delaying disease progression and death.
                          (3) CPCRA 042, NvR: To compare the effect of
                          2 antiretroviral treatments, 1 starting with
                          combination therapy including nelfinavir
                          (NFV) and the other starting with combination
                          therapy including ritonavir (RTV), in
                          delaying disease progression and death [AS
                          PER AMENDMENT 2/28/01: in delaying mortality]
                          in HIV-infected patients with CD4 cell counts
                          less than 200 cells/mm3. (4) CPCRA 057, PIP:
                          To compare the effects of using efavirenz
                          (EFV) alone, with a single protease inhibitor
                          (PI) or with a double PI on disease
                          progression and death among patients failing
                          on NFV, indinavir (IDV), or RTV. (5) CPCRA
                          046 and 039, GART and bis-POM: To evaluate
                          the prognostic importance for delaying
                          disease progression and death of genotypic
                          resistance patterns. [AS PER AMENDMENT
                          2/28/01: The fourth and fifth objectives
                          listed above are no longer included. (6)
                          CPCRA 064, MDR-HIV: To compare the effect of
                          a strategy of prescribing a 4-month
                          antiretroviral structured treatment
                          interruption followed by initiating a new
                          antiretroviral regimen versus a strategy of
                          immediately initiating a new antiretroviral
                          regimen in delaying mortality in patients
                          with multidrug-resistant HIV. (7) All other
                          qualifying protocols: To compare the effects
                          of the randomized interventions in delaying
                          disease progression and death.]
GENERAL DESCRIPTION       RATIONALE: Highly active antiretroviral
                          therapy (HAART) often results in short-term
                          benefits for people with HIV in terms of
                          reduced plasma viral levels and increased CD4
                          cell counts. When used at an early stage of
                          HIV disease, however, the clinical benefit of
                          HAART is uncertain. Many questions still
                          remain regarding the optimal use of
                          antiretroviral therapies, such as the timing
                          of initial antiretroviral therapy and the
                          composition of the best combination regimen
                          to use initially or after virologic failure.
                          Randomized trials of different starting
                          antiretroviral regimens (e.g., FIRST [CPCRA
                          058]), different regimens after initial
                          virologic failure (e.g., PIP [CPCRA 057]),
                          and different management strategies for HIV
                          infection (e.g., bis-POM [CPCRA 039], NvR
                          [CPCRA 042], GART [CPCRA 046], and IL-2
                          VL/Dose [CPCRA 059] are being conducted by
                          the CPCRA. [AS PER AMENDMENT 2/28/01: The
                          MDR-HIV (CPCRA 064) protocol is now included
                          as an example of a different management
                          strategy for HIV infection, whereas the
                          bis-POM (CPCRA 039) protocol is no longer
                          included.] This study provides a mechanism
                          for long-term monitoring of patients enrolled
                          in these trials as well as
                          antiretroviral-naive patients who are either
                          starting treatment or electing to defer
                          treatment.
GENERAL DESCRIPTION       METHODOLOGY: Patients are divided into 3
                          groups. Group A consists of patients
                          currently enrolled in or currently being
                          followed in an ongoing qualifying study (see
                          Purpose for CPCRA trials which qualify).
                          Group B consists of patients previously
                          enrolled in but not currently being followed
                          in a qualifying study. Group C consists of
                          antiretroviral-naive patients not enrolling
                          in a qualifying study (i.e., patients
                          starting treatment outside the FIRST study or
                          patients deferring treatment). Patients in
                          Group A undergo monitoring of selected
                          clinical and laboratory parameters (including
                          plasma HIV RNA levels and CD4 cell counts)
                          once every 4 weeks beginning after completion
                          of all follow-up appointments for all other
                          protocols in which they were enrolled.
                          Patients in Groups B and C undergo monitoring
                          of selected clinical and laboratory
                          parameters (including plasma HIV RNA levels
                          and CD4 cell counts) once every 4 months.
                          Patients are followed for at least 5 years.
                          [AS PER AMENDMENT 2/28/01: Patients who are
                          not being followed in a qualifying protocol
                          and are antiretroviral naive at enrollment or
                          were previously enrolled in the FIRST (CPCRA
                          058) protocol undergo blood draws at
                          enrollment and then annually for measurement
                          of plasma HIV levels by a CPCRA-approved
                          laboratory and future CPCRA-approved,
                          HIV-related research. Patients who relocate
                          to a non-CPCRA affiliated site are asked to
                          sign a consent for ongoing release (every 4
                          months) of their medical records from their
                          new health care provider to the CPCRA.].
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Clinical Evaluation.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 3700 patients. 1,000 from
                          the FIRST (CPCRA 058) protocol; 470 from the
                          NvR (CPCRA 042) protocol; 720 from the PIP
                          (CPCRA 057) protocol; 450 from the IL
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 5
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 2642/3700 010731.
PROTOCOL DETAILS          STUDY DURATION: At least 5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 17
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (010228)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. A working diagnosis of HIV
                          infection, based on medical history, clinical
                          evaluation, or results of laboratory tests.
                          2. Either (a) no previous experience with
                          antiretroviral therapy, defined as no
                          previous protease inhibitor (PI) or
                          non-nucleoside reverse transcriptase
                          inhibitor (NNRTI) use, 1 week or less of
                          lamivudine (3TC) use, and 4 weeks or less of
                          cumulative nucleoside reverse transcriptase
                          inhibitor (NRTI) use, or (b) current or
                          previous enrollment in a qualifying trial. 3.
                          Signed informed consent of parent or guardian
                          if under 18 years. (NOTE: It is recommended
                          but not required that antiretroviral-naive
                          patients entering this trial be in reasonably
                          good health at the time of study entry, with
                          a perceived life expectancy of at least 6
                          months. [AS PER AMENDMENT 2/28/01: This
                          recommendation has been changed to a general
                          guideline.] Patients should be capable, in
                          the clinician's opinion, of complying with
                          the protocol.).
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Required: Either no
                          previous antiretroviral treatment (defined as
                          no previous PI or NNRTI use, 1 week or less
                          of 3TC use, and 4 weeks or less of NRTI use)
                          or current or previous enrollment in a
                          qualifying trial.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
OTHER TREATMENT INFO.     END POINT: Clinical progression of HIV
                          disease, including death.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Community Consortium / UCSF 3180 18th St /
                          Suite 201 San Francisco, CA 94110 Carroll
                          Child [phone] Recruiting 990623.
COLORADO                  Denver CPCRA / Denver Public Hlth 605 Bannock
                          St Denver, CO 802044507 Jack Rouff
                          [phone] Recruiting PEND 990513.
CONNECTICUT               Yale U / New Haven Med Ctr / AIDS Clinical
                          Trials Unit 135 College St / Suite 323 New
                          Haven, CT 065102483 Laurie Andrews
                          [phone] No longer recruiting 010612.
DISTRICT OF COLUMBIA      Washington Reg AIDS Prog / Dept of Infect Dis
                          VA Med Ctr / 50 Irving St NW Washington, DC
                          20422 Barbara Standridge [phone] No
                          longer recruiting PEND 000111.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon Ave / Suite 130 Atlanta, GA 303081962
                          Melanie Thompson MD [phone] No longer
                          recruiting 010528.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd #108 Chicago, IL 60657 Rita
                          Verheggen [phone] Recruiting PEND
                          990513.
LOUISIANA                 Louisiana Comm AIDS Rsch Prog / Tulane Univ
                          Med 1430 Tulane Ave / TB 21 New Orleans, LA
                          70112 Janice Walker [phone] Recruiting
                          PEND 990602.
MICHIGAN                  Henry Ford Hosp 2799 West Grand Blvd /
                          CFP-104 Detroit, MI 48202 Diane Mastro-Polak
                          [phone] Recruiting 990513.
MICHIGAN                  Wayne State Univ - WSU/DMC / Univ Hlth Ctr
                          4201 Saint Antoine / POD 7C Detroit, MI 48201
                          Jan Kosmyna [phone] Recruiting 990623.
NEW JERSEY                Southern New Jersey AIDS Clinical Trials Dept
                          of Medicine / 3 Cooper Plaza / Suite 513
                          Camden, NJ 08103 Carol Graeber [phone]
                          Recruiting PEND 990602.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Robert C Sawyer [phone]
                          Recruiting PEND 990513.
NEW MEXICO                Partners in Research / New Mexico 915 Camino
                          de Salud NE Albuquerque, NM 87131 Cynthia
                          Nicholson [phone] Recruiting PEND
                          990602.
NEW YORK                  Harlem AIDS Treatment Grp / Harlem Hosp Ctr
                          506 Lenox Ave / Rm 3101A New York, NY 10037
                          Luis Fuentes [phone] Recruiting 990623.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn St Portland, OR 97210 Norma Martinez
                          [phone] Recruiting 990713.
PENNSYLVANIA              Philadelphia FIGHT 1233 Locust St / 5th Floor
                          Philadelphia, PA 19107 Jane Shull
                          [phone] Recruiting PEND 990510.
TEXAS                     Univ TX Health Science Ctr 6431 Fannin St
                          Houston, TX 77030 Hilda Cuervo [phone]
                          Recruiting 001101.
VIRGINIA                  Richmond AIDS Consortium / Div of Infect
                          Diseases PO Box 980049 Richmond, VA 232980049
                          Vinnie Mitchell [phone] Recruiting PEND
                          990602.

119
UNIQUE IDENTIFIER         NIH/01112
PROTOCOL ID NUMBERS       NIAID HIVNET 015
PROTOCOL TITLE            A Randomized Clinical Trial of the Efficacy
                          of a Behavioral Intervention to Prevent
                          Acquisition of HIV Among Men Who Have Sex
                          with Men.
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy of a
                          behavioral intervention to reduce
                          seroincidence of HIV infections in a
                          population of men who have sex with men
                          (MSM). Specifically, three-year seroincidence
                          of HIV infections observed in a sample of MSM
                          randomized to the behavioral intervention is
                          compared with that observed in MSM randomized
                          to the control condition (standard HIV
                          pre-test and post-test risk reduction
                          counseling based on the Centers for Disease
                          Control and Prevention/Project RESPECT
                          model).
GENERAL DESCRIPTION       RATIONALE: The intervention being evaluated
                          in this trial is based on the extensive
                          literature on behavioral approaches to risk
                          reduction in MSM. These reviews recommend an
                          intervention that, unlike the current
                          standard HIV pre-test and post-test
                          risk-reduction counseling, is tailored to an
                          individual's unique problems and needs,
                          lifestyle, and situations that contribute to
                          high-risk behavior. Furthermore, there is a
                          need for HIV-prevention intervention trials
                          using biological endpoints (e.g., HIV
                          seroconversion) in addition to behavioral
                          change indices.
GENERAL DESCRIPTION       METHODOLOGY: Participants are randomly
                          assigned to receive either the behavioral
                          intervention or the control risk-reduction
                          counseling. The same counseling staff
                          provides the two types of treatment. The
                          behavioral intervention consists of 10
                          counseling sessions within a 4-month period
                          followed by quarterly maintenance sessions
                          for the remainder of the 3-year follow-up.
                          The intervention is conducted on a one-to-one
                          basis and targets condom use, change in
                          sexual practices associated with HIV risk,
                          and change in sexual practices in the context
                          of alcohol and drug use. Participants in the
                          control group receive pre- and post-test
                          counseling at enrollment, then semiannually
                          through Month 36. Beginning at Month 6, all
                          participants complete routine semiannual
                          visits. At each visit, Risk Assessment and
                          phlebotomy for specimen collection for HIV
                          antibody tests are administered. As is
                          routine in most public counseling and testing
                          venues, participants in the control condition
                          do not see the same counselor consistently.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Primary prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 4350 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 4295/4350 010301.
PROTOCOL DETAILS          STUDY DURATION: 4 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6
PROTOCOL DETAILS          VERSION NUMBER & DATE: 2 (981218)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study;
                          Placebo-Controlled Trial; Random Allocation;
                          Parallel Designs
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants must
                          have: 1. HIV-seronegativity, as documented by
                          licensed ELISA or by Western blot if found to
                          be HIV-seropositive by licensed ELISA. 2.
                          Willingness and ability to participate in all
                          scheduled study visits and tests. 3.
                          Willingness and ability to provide adequate
                          information for locator purposes.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   RISK BEHAVIOR: Included: Reported anal
                          intercourse (receptive, insertive, protected
                          or unprotected) with another man in the 12
                          months prior to enrollment.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT SEX               MALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Participants with
                          the following symptoms and conditions are
                          excluded: In a mutually monogamous
                          relationship for two years or more with a
                          known HIV antibody-negative male. Monogamous
                          is defined as a relationship in which the
                          members of the couple engage in sexual
                          activities only with each other, excluding
                          all others.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Enrollment in the
                          HIVNET 015 Pilot Study.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Enrollment in
                          HIVNET Protocol 014.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Enrollment
                          in any Phase III HIV vaccine trial, including
                          the AIDSVAX Phase III trial sponsored by
                          VaxGen, Inc.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Participants with the
                          following symptoms and conditions are
                          excluded: Any obvious
                          psychological/psychiatric disorder or other
                          condition that would contraindicate
                          participation and interfere with study
                          objectives.
OTHER TREATMENT INFO.     END POINT: HIV seroincidence.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                San Francisco Dept of Hlth / AIDS Office 25
                          Van Ness Ave / Suite 500 San Francisco, CA
                          94102 Joe Wright [phone] Recruiting
                          990413.
COLORADO                  Denver Dept of Public Health / HIVNET 605
                          Bannock St / Room 220 Denver, CO 80204 Ken
                          Miller [phone] Recruiting 990413.
ILLINOIS                  Howard Brown Health Ctr 4025 North Sheridan
                          Rd Chicago, IL 60613 David McKirnan
                          [phone] Recruiting 990413.
MASSACHUSETTS             Fenway Community Health Ctr 7 Haviland St
                          Boston, MA 02115 Dr Ken Mayer [phone]
                          Recruiting 990413.
NEW YORK                  New York Blood Ctr Project ACHIEVE / 1309
                          Fulton Ave Room 312 Bronx, NY 10456 Cladd
                          Stevens [phone] Recruiting 990413.
WASHINGTON                Univ of Washington 901 Boren Ave Suite 1300
                          UW Box 3599227 Seattle, WA 98104 Dennis
                          Torres [phone] Recruiting 990413.

120
UNIQUE IDENTIFIER         NIH/01098
PROTOCOL ID NUMBERS       CC 91 I-0140
PROTOCOL TITLE            Studies of the Pathogenesis of HIV Infection
                          in Human Peripheral Blood Cells.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To study the pathogenesis of HIV
                          infection using human peripheral blood
                          mononuclear cells as a model. Methodology:
                          This study utilizes human peripheral blood
                          cells to study aspects of either in vivo or
                          in vitro HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: This study utilizes human
                          peripheral blood cells to study aspects of
                          either in vivo or in vitro HIV infection.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          PROJECTED ACCRUAL: patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 cell count
                          greater than 200 cells/mm3. 3. Adequate
                          venous access. 4. No significant medical
                          problems except HIV.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 200 cells/mm3.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding Not
                          pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to 65 years.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded:
                          Anti-coagulants.
OTHER TREATMENT INFO.     END POINT: Pathogenic aspects of HIV
                          infection.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA ACCRUAL 990303.

121
UNIQUE IDENTIFIER         NIH/01094
PROTOCOL ID NUMBERS       CC 99 I-0032
PROTOCOL TITLE            HAART versus HAART Plus Interleukin 2 (IL-2)
                          in Primary, Recently Seroconverted
                          HIV-Infected Patients.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
PROTOCOL CHAIRS           CHAIR  Richard Davey
GENERAL DESCRIPTION       PURPOSE: To examine the ability of highly
                          active antiretroviral therapy (HAART) in
                          combination with interleukin-2 (IL-2) to
                          reduce the reservoir of latent virus in
                          resting CD4+ T cells and restore components
                          of the immune system. To provide immunologic
                          and virologic characterization of changes
                          occurring in HIV-seropositive patients and
                          patients with primary HIV infection receiving
                          either HAART plus IL-2 or HAART alone.
GENERAL DESCRIPTION       RATIONALE: Although HAART has been successful
                          in controlling plasma HIV viral levels and
                          replication in infected patients, it has not
                          been able to eradicate the latent virus from
                          the resting CD4+ T cell compartment. In
                          addition, the effects of HAART on immunologic
                          restoration have been comparatively modest.
                          It is believed that the use of immune
                          modulators in combination with antiretroviral
                          agents may represent an important approach to
                          immune reconstitution and viral eradication.
                          Therefore, IL-2 is being studied for its
                          potential role in supplementing HAART.
GENERAL DESCRIPTION       METHODOLOGY: Patients are enrolled into 1 of
                          3 cohorts. Patients in Cohorts 1 and 2 are
                          randomized to receive HAART plus IL-2 (Arm I)
                          or HAART alone (Arm II). Patients in Cohort 1
                          are referred to the study team through a
                          CPCRA study with their treatment determined
                          and administered under the auspices of that
                          protocol. [AS PER AMENDMENT 12/08/99: Cohort
                          1 never enrolled patients and is terminated.]
                          Cohort 2 consists of patients in the early
                          stages of HIV infection with their treatment
                          determined under the auspices of this
                          protocol. Cohort 3 consists primarily of
                          patients who are receiving HAART plus IL-2 or
                          are IL-2 naive and eligible to receive HAART
                          plus IL-2. All patients in Cohort 3 take
                          HAART plus IL-2. Patients in Cohorts 1 to 3
                          are required to take antiretroviral
                          medications satisfying a reasonable
                          definition of HAART, as per the judgment of
                          the study team. The specific composition of
                          HAART is left to the discretion of the
                          treating clinician for patients in Cohorts 1
                          and 3. Patients in Cohort 2 receive an
                          initial 4-drug regimen consisting of
                          stavudine (or zidovudine), lamivudine,
                          indinavir (or nelfinavir), and efavirenz (or
                          nevirapine). IL-2 is provided and clinical
                          care offered to patients in Arm I of Cohort 2
                          as well as to patients in Cohort 3 if not
                          provided under another protocol. IL-2 is
                          administered twice daily for 5 consecutive
                          days in 8-week cycles. Study participants are
                          taught to self-administer the doses. For
                          patients in Arm I of Cohort 2 and IL-2-naive
                          patients in Cohort 3, cycles of IL-2 begin
                          once plasma HIV RNA levels are documented and
                          confirmed below 50 copies/ml while on HAART
                          therapy. [AS PER AMENDMENT 10/27/99: Viral
                          load must be below 1,000 copies/ml for IL-2
                          therapy.] Patients in Arm I of Cohort 2 and
                          IL-2 naive patients in Cohort 3 receive at
                          least 3 cycles during the first 6 months
                          following randomization. After 3 cycles,
                          treatment is guided on an individual basis
                          determined by CD4 cell count. Throughout the
                          study, periodic sampling of peripheral blood,
                          leukapheresis, and, in Cohort 2, optional
                          lymph node biopsies are performed to compare
                          virologic and immunologic responses between
                          the treatment arms.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Immunotherapy,
                          Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 130 patients. Cohort 1:
                          200 patients; Cohort 2: 30 patients; Cohort
                          3: 100 patients. [AS PER AMENDMENT 12/08/99:
                          Cohort 1 never enrolled and is termina
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Open-ended.
                          Patients in Cohorts 2 and 3 maintain
                          participation as long as there appears to be
                          a clinical benefit to treatment, as judged by
                          the principal investigator. Patients in
                          Cohort 1 continue with this study for as long
                          as they are partici
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/130.
PROTOCOL DETAILS          STUDY DURATION: Open-ended.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          VERSION NUMBER & DATE: (001204)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: IRP 024
PROTOCOL DETAILS          STUDY DESIGN: Open Label; Randomized Control
                          Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: All patients must
                          have: 1. HIV-1 infection documented by any
                          licensed ELISA test kit and confirmed by a
                          second method (e.g., Western blot); or by HIV
                          culture, HIV p24 antigen, plasma HIV RNA, or
                          proviral HIV DNA. 2. CD4 cell count of at
                          least 300 cells/mm3 within 30 days before
                          randomization. (For patients who are status
                          post-splenectomy, also a CD4 cell percentage
                          greater than 20 percent.) Patients in Cohort
                          2 must have: In addition to the above
                          criteria, HIV preseroconversion or
                          periseroconversion (within 3 to 6 months)
                          status, determined at the discretion of the
                          principal investigator or designate. A
                          documented history of symptomatic primary HIV
                          infection with a positive viral load or p24
                          antigen test and a negative ELISA from a CLIA
                          certified laboratory within this time frame,
                          or at least a history with supporting
                          laboratory data consistent with this time
                          frame, would generally be sufficient.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 300 cells/mm3 For
                          patients status post-splenectomy, a CD4 cell
                          % > 20%.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN ULN (Upper Limit of
                          Normal). Unless there is a pattern consistent
                          with Gilbert's syndrome or the patient is
                          receiving indinavir.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 mg/dl.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test within 14 days of
                          study entry Abstinence or effective method of
                          birth control / contraception including oral
                          contraceptives during the study.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Required:
                          Antiretroviral therapy which can include
                          agents (approved or investigational)
                          administered through routine care or through
                          participation in clinical trials or expanded
                          access programs. Patients in Cohort 2 must
                          receive antiretrovirals as outlined in this
                          protocol. Allowed with caution: Nephrotoxic,
                          myelotoxic, cardiotoxic, and hepatotoxic
                          agents. Allowed with careful monitoring:
                          Psychotropic drugs (e.g., narcotics,
                          analgesics, antiemetics, sedatives, and
                          tranquilizers).
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of Crohn's disease, psoriasis, [AS
                          PER AMENDMENT 12/8/99: optic neuritis,] or
                          other autoimmune/inflammatory diseases with
                          potentially life-threatening complications.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active substance
                          abuse or history of prior substance abuse
                          that may interfere with protocol compliance
                          or compromise patient safety.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded for all patients:
                          Systemic corticosteroids, immunosuppressants,
                          or experimental cytotoxic agents (including
                          hydroxyurea) within 4 weeks prior to study
                          randomization. Excluded for Cohorts 1 and 2:
                          IL-2 therapy. [AS PER AMENDMENT 12/08/99:
                          Cohort 1 never enrolled patients and is
                          terminated.].
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Cytotoxic
                          agents, approved or experimental, during the
                          5-day administration of IL-2, with the
                          possible exception of hydroxyurea. Generally
                          avoided: Beta-blockers and other
                          antihypertensives.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy, or any other disease state,
                          requiring cytotoxic chemotherapy. 2.
                          Symptomatic for significant HIV-related
                          illnesses, such as opportunistic infections
                          and malignancies other than mucocutaneous
                          Kaposi's sarcoma. 3. Any central nervous
                          system (CNS) abnormality that requires
                          treatment with antiseizure medication. 4.
                          Crohn's disease, psoriasis, or other
                          autoimmune/inflammatory diseases with
                          potentially life-threatening complications.
                          5. Significant cardiac, pulmonary, kidney,
                          rheumatologic, gastrointestinal, or CNS
                          disease as detectable on routine history,
                          physical examination, or screening laboratory
                          studies. 6. Psychiatric illness that, in the
                          opinion of the principal investigator, might
                          interfere with study compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Aldesleukin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0269  Efavirenz
SUBSTANCE IDENTIFICATION  Drug 8  DRG-0116  Nevirapine
RESULTS                   Dybul M, Chun TW, Belson M, Hidalgo B, Herpin
                          B, Perry C, Hallahan C, Metcalf J, Davey R,
                          Fauci AS. 8th Conf Retro and Opportun Infect.
                          2001 Feb 4-8 (abstract no. 406).
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 7.5 MIU twice daily
                          for 5 consecutive days every 8 weekDrug 2:
                          30-40 mg bid (depending on weight). Drug 3:
                          300 mg bid. Drug 4: 150 mg bid. Drug 5: 1,000
                          mg tid. Drug 6: 750 mg tid. Drug 7: 600 mg
                          qd. Drug 8: 200 mg qd for 14 days, then bid
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 2: 60-80 mg. Drug 3: 600
                          mg. Drug 4: 300 mg. Drug 5: 3,000 mg. Drug 6:
                          2,250 mg. Drug 7: 600 mg. Drug 8: 200 mg for
                          14 days, then 400 mg
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Subcutaneous. Drug 2:
                          Oral. Drug 3: Oral. Drug 4: Oral. Drug 5:
                          Oral. Drug 6: Oral. Drug 7: Oral. Drug 8:
                          Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Open-ended.
OTHER TREATMENT INFO.     END POINT: Viral load; immunologic profile,
                          including CD4 cell count.
OTHER TREATMENT INFO.     DISCONTINUE: Patients who experience any of
                          the following events or conditions should
                          have their IL-2 cycles delayed: 1. IL-2
                          toxicity requiring temporary discontinuation.
                          2. Pregnancy or breast-feeding. 3.
                          Intercurrent illness that, in the judgment of
                          the clinician, would significantly affect
                          assessment of clinical status. 4. Use of
                          cytotoxic agents, approved or experimental,
                          for any reason. 5. HAART regimen is
                          interrupted for any reason. Patients who
                          experience any of the following events or
                          conditions are permanently discontinued from
                          IL-2: 1. IL-2 toxicity requiring permanent
                          discontinuation. 2. Development of
                          life-threatening infection or malignancy. 3.
                          Development of serious HIV-related illness.
                          4. Permanent discontinuation of all
                          antiretroviral drugs. 5. Inability to
                          tolerate procedures or study requirements. 6.
                          Patient requests discontinuation of study
                          treatment. 7. Principle investigator feels it
                          is in the patient's best interest.
OTHER TREATMENT INFO.     MODIFICATION: Patients will delay their IL-2
                          cycle in the event of: 1. IL-2 toxicity. If a
                          patient experiences dose-limiting toxicity
                          (DLT) during the 5-day administration of
                          IL-2, the remaining IL-2 doses are held until
                          the DLT has decreased in severity to Grade 2
                          or less and is no longer considered
                          dose-limiting. At this point, the patient may
                          have the IL-2 dose reduced for the remainder
                          of the 5-day cycle. Subsequent cycles are
                          initiated at a dose below the level that gave
                          rise to the DLT during the previous cycle. 2.
                          Pregnancy or breast-feeding. 3. Intercurrent
                          illness that, in the judgment of the
                          clinician, would significantly affect the
                          assessment of clinical status. 4. Use of
                          cytotoxic agents, approved or experimental,
                          for any reason. 5. Interruption of HAART
                          regimen for any reason. To continue IL-2
                          treatments, patients must be willing and able
                          to restart HAART at least 1 day prior to a
                          cycle and continuing through to at least 9
                          days after completion of the cycle.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA accrual 000620.

122
UNIQUE IDENTIFIER         NIH/01087
PROTOCOL ID NUMBERS       NIAID ACTG 381
PROTOCOL TITLE            Establishment and Maintenance of Long-Term
                          Undetectable Plasma HIV-1 RNA: Correlation
                          with Immunologic Reconstitution and Viral
                          Dynamics.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
PROTOCOL CHAIRS           CHAIR  Patricia Flynn
GENERAL DESCRIPTION       PURPOSE: To determine if a positive
                          correlation exists between the baseline
                          immunologic status and the virologic and
                          immunologic responses to highly active
                          antiretroviral therapy (HAART) at 1, 2, and 3
                          years after initiation of treatment.
GENERAL DESCRIPTION       RATIONALE: Recent adult clinical trials
                          involving combination HAART, including a
                          protease inhibitor (PI), have demonstrated
                          improvements in somatic immune system
                          functioning. [AS PER AMENDMENT 2/27/01: More
                          recently, similar success has been
                          demonstrated with a PI-sparing regimen,
                          zidovudine, lamivudine, and efavirenz.] Not
                          all individuals, however, experience the same
                          level of immune reconstitution, and
                          oftentimes any improvement is short-lived.
                          Adolescent patients may have a greater
                          potential for immune restoration because of
                          residual thymic tissue and therefore may
                          experience greater long-term virus-free
                          states as compared to adult patients. This
                          study examines the duration of virologic
                          efficacy HAART has on the adolescent
                          HIV-positive population.
GENERAL DESCRIPTION       METHODOLOGY: Patients begin study by
                          initiating a HAART regimen of a minimum of 3
                          drugs, at least 1 of which must be a PI [AS
                          PER AMENDMENT 2/27/01: or efavirenz (EFV)]. A
                          variety of drug combinations are used;
                          therefore, patients are grouped according to
                          the classes of drugs in their respective
                          regimen (e.g., 2 nucleoside reverse
                          transcriptase inhibitors [NRTIs] plus 1 PI; 2
                          NRTIs plus 2 PIs; 1 or 2 NRTIs plus 1 PI plus
                          1 nonnucleoside reverse transcriptase
                          inhibitor [NNRTI] [AS PER AMENDMENT 2/27/01:
                          ; and 2 NRTIs plus EFV]). At the time of
                          HAART initiation, patients undergo
                          immunologic and virologic assessments in
                          order to determine baseline values. Then, to
                          determine the virologic success or failure of
                          HAART, HIV-1 RNA measurements are taken and
                          compared to initial baseline values.
                          Virologic success equals undetectable HIV-1
                          RNA at Week 12 [AS PER AMENDMENT 2/27/01: and
                          confirmed at Week 16] or a significant
                          (greater than 1 log) decrease in HIV-1 RNA
                          from baseline to Week 12 [AS PER AMENDMENT
                          2/27/01: and confirmed undetectable HIV-1 RNA
                          before the next scheduled visit (Week 24)].
                          Patients are followed for a minimum of 3
                          years of maintained viral suppression or
                          until they have demonstrated virologic
                          failure. From these values, any correlation
                          that may exist between HIV-1 RNA values and
                          HAART can be deduced. Patients with virologic
                          failure on the initial HAART regimen may be
                          allowed to change to a second HAART regimen.
                          [AS PER AMENDMENT 2/27/01: Patients with
                          virologic success on the second HAART regimen
                          are followed for a minimum of 3 years.]
                          Patients with virologic failure on the second
                          HAART regimen or who voluntarily discontinue
                          HAART are followed using an abbreviated
                          schedule for 3 years.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Immunology, Clinical
                          Evaluation, Viral load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 120 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 110/120 010731.
PROTOCOL DETAILS          STUDY DURATION: About 5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 46
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (010329)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 381
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Longitudinal
                          Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection as documented by any
                          licensed ELISA test kit and confirmed by
                          either Western blot, HIV culture, HIV
                          antigen, plasma HIV-1 RNA PCR, or a second
                          antibody test other than ELISA. 2. Parental
                          consent for patients under age 18. [3. AS PER
                          AMENDMENT 2/27/01: Life expectancy of at
                          least 1 year.].
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study and for 90
                          days after Pregnancy allowed under certain
                          conditions. See 'Inclusion - General
                          Criteria' section.
PATIENT INCLUSION CRIT.   OTHER: [Included: AS PER AMENDMENT 2/27/01:
                          Women who are receiving EFV and become
                          pregnant during the study must switch to
                          another NNRTI or a PI for the duration of the
                          pregnancy. Women who are receiving ddI/d4T
                          and become pregnant must switch to at least 1
                          other NRTI for the duration of the
                          pregnancy.].
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: Monotherapy with
                          an antiretroviral if plasma HIV-1 RNA is
                          detectable within 30 days of study entry.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 08
                          years less than or equal to 22 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following conditions are excluded: 1.
                          Perinatal transmission of HIV infection. 2.
                          Previous enrollment on this protocol and
                          failure of initial and alternate HAART
                          regimens. 3. Acquired HIV infection by
                          transfusion during the perinatal period. [4.
                          AS PER AMENDMENT 2/27/01: AIDS-defining
                          opportunistic infection at the time of
                          screening.].
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Receipt of
                          immunotherapy including HIV vaccines, HIVIG,
                          or cytokine therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. HAART or
                          combination therapy. [2. AS PER AMENDMENT
                          2/27/01: ddI/d4T or EFV for patients who are
                          pregnant.].
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Undetectable
                          plasma HIV-1 RNA [AS PER AMENDMENT 2/27/01:
                          with O.D. less than 0.2 by Roche Amplicor
                          assay]. 2. Co-enrollment with studies using
                          HIV vaccines, HIVIG, or cytokine therapy. [3.
                          AS PER AMENDMENT 2/27/01: Pregnant women who
                          are taking didanosine/stavudine (ddI/d4T) or
                          EFV as part of their HAART regimen.].
RESULTS                   Flynn P, Douglas S, Rudy B, Lathey J, Lindsey
                          J, Wang Y. 8th Conf Retro and Opportun
                          Infect. 2001 Feb 4-8 (abstract no. 692).
OTHER TREATMENT INFO.     TREATMENT DURATION: 3 years.
OTHER TREATMENT INFO.     END POINT: Viral load, CD4 cell count.
OTHER TREATMENT INFO.     DISCONTINUE: [AS PER AMENDMENT 2/27/01: Women
                          who are receiving EFV and become pregnant
                          during the study must switch to another NNRTI
                          or a PI for the duration of the pregnancy.
                          Women who are receiving ddI/d4T and become
                          pregnant must switch to at least 1 other NRTI
                          for the duration of the pregnancy.].
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] No longer
                          recruiting 010222.
ALABAMA                   Univ of South Alabama 1504 Springhill Avenue
                          Mobile, AL 36604 Julie Bebawy [phone]
                          Recruiting 990802.
ARIZONA                   Phoenix Childrens Hosp 909 East Brill Street
                          Phoenix, AZ 85006 Laura Clarke-Steffan
                          [phone] Recruiting 010621.
CALIFORNIA                Children's Hosp of Los Angeles/UCLA Med Ctr
                          4650 Sunset Blvd Los Angeles, CA 900276016
                          Zane O'Keefe [phone] Recruiting 990917.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 990917.
CALIFORNIA                UCSD Med Ctr / Pediatrics / Clinical Sciences
                          9500 Gilman Dr La Jolla, CA 920930672 Candace
                          McIvor [phone] Recruiting 990330.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 990719.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 990414.
CONNECTICUT               Connecticut Children's Med Ctr 263 Farmington
                          Ave Farmington, CT 060303805 Gail Karas
                          [phone] Recruiting 000404.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 990623.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 990329.
FLORIDA                   Univ of Florida Gainesville 1600 Archer Rd /
                          SW Gainesville, FL 32610 Carol Delany
                          [phone] Recruiting 000726.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 990623.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          990917.
FLORIDA                   Palm Beach County Health Dept 301 Broadway
                          Riviera Beach, FL 33404 Patricia Vann
                          [phone] Recruiting 990917.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 990402.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 990707.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          990917.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] No longer
                          recruiting 010130.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 990706.
LOUISIANA                 Earl K Long Early Intervention Clinic 1430
                          Tulane Ave TB-8 New Orleans, LA 70112 Kim
                          Anglin [phone] Recruiting 990917.
MASSACHUSETTS             Children's Hosp of Boston 300 Longwood Ave /
                          Carnegie Building Boston, MA 021155724 Robert
                          Holt [phone] Recruiting 990408.
MASSACHUSETTS             Boston City Hosp / Pediatrics 774 Albany St /
                          Finland Lab / Room 301 Boston, MA 02118 Anne
                          Marie Regan [phone] Recruiting 990917.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 990407.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] No longer recruiting 001110.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 990405.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 990730.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 990917.
NEW YORK                  SUNY - Brooklyn 450 Clarkson Ave / Box 49
                          Brooklyn, NY 11203 Denise Swindell
                          [phone] No longer recruiting 010307.
NEW YORK                  Incarnation Children's Ctr / Columbia
                          Presbyterian Med Ctr 622 West 168th St New
                          York, NY 10032 Marie Donahue [phone]
                          Recruiting 990615.
NEW YORK                  North Shore Univ Hosp 865 Northern Boulevard
                          / Suite 104 Great Neck, NY 11021 Lourdes
                          Rodriguez [phone] Recruiting 990719.
NEW YORK                  Bellevue Hosp / New York Univ Med Ctr 550
                          First Ave New York, NY 10016 Nagamah Deygoo
                          [phone] Recruiting 001121.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 990615.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          990917.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] Recruiting 010318.
NEW YORK                  Montefiore Med Ctr Adolescent AIDS Program
                          111 East 210th St Bronx, NY 10467 Dina Monte
                          [phone] Recruiting 990917.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 990809.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          990512.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 990412.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] No longer recruiting 010507.
PENNSYLVANIA              Children's Hosp of Philadelphia 34th St &
                          Civic Ctr Blvd Philadelphia, PA 191044318
                          Carol Vincent [phone] Recruiting
                          990412.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          990202.
TEXAS                     Texas Children's Hosp / Baylor Univ 6621
                          Fannin St / MC1-3291 Houston, TX 77030
                          Kathryn Owl [phone] Recruiting 991004.
TEXAS                     Children's Med Ctr of Dallas 1935 Motor St
                          Dallas, TX 75235 Diane Ramirez [phone]
                          Recruiting 990706.
VIRGINIA                  Children's Hosp of the King's Daughters 601
                          Children's Lane Norfolk, VA 23507 Donna
                          Sandifer [phone] Recruiting 990716.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 990917.

123
UNIQUE IDENTIFIER         NIH/01086
PROTOCOL ID NUMBERS       NIAID CPCRA 058
PROTOCOL TITLE            A Randomized, Open-Label Study of the
                          Long-Term Effectiveness of Three Initial
                          Highly Active Antiretroviral Therapy (HAART)
                          Strategies in HAART-Naive, HIV-Infected
                          Persons.
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Rodger MacArthur
PROTOCOL CHAIRS           CO-CHAIR  Douglas Mayer
GENERAL DESCRIPTION       PURPOSE: To compare the effects of 3 HAART
                          strategies on long-term HIV RNA levels. To
                          evaluate which of these antiretroviral (AR)
                          treatment regimens is the most effective
                          initial treatment for HIV infection. To
                          assess the number of and reasons for changes
                          in AR treatment regimens.
GENERAL DESCRIPTION       RATIONALE: Treatment with HAART regimens
                          containing protease inhibitors (PIs) or
                          nonnucleoside reverse transcriptase
                          inhibitors (NNRTIs) has been shown to slow
                          disease progression. However, the long-term
                          consequences of initial therapy with a PI, an
                          NNRTI, or both a PI and an NNRTI are not yet
                          known, nor is the impact on future AR
                          treatment regimens. Patients who experience
                          virologic failure on a particular HAART
                          regimen typically have not been studied for
                          subsequent response to other HAART regimens.
                          It is possible that a regimen which is
                          initially the most potent may not be optimal
                          if it limits the effectiveness of subsequent
                          AR therapies.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to 1 of
                          3 HAART treatment arms: Arm 1: 1 or 2 PIs
                          plus 2 nucleoside reverse transcriptase
                          inhibitors (NRTIs). Arm 2: 1 NNRTI plus 2
                          NRTIs. Arm 3: 1 or 2 PIs plus an NNRTI plus 1
                          or 2 NRTIs. Before randomization to a
                          treatment arm, patients are given the option
                          of pre-selecting the drugs they will use or
                          allowing randomization to study-specified
                          drugs. The study-specified PIs are indinavir
                          (IDV), nelfinavir (NFV), or 2 PIs of patient
                          and doctor choice. The study-specified NNRTIs
                          are nevirapine (NVP) or efavirenz (EFV). The
                          choice of NRTIs is decided by the doctor. [AS
                          PER AMENDMENT 9/9/99: The study-specified
                          NRTIs are abacavir (ABC) plus lamivudine
                          (3TC) or didanosine (ddI) plus stavudine
                          (d4T).] This study involves only medical
                          follow-up and evaluation of blood tests; all
                          drugs are obtained by clinician prescription.
                          [AS PER AMENDMENT 9/9/99: ABC and 3TC are
                          provided to all patients who are taking both
                          ABC and 3TC. All patients who are taking
                          either or both ddI and d4T are provided with
                          ddI and/or d4T. All other AR drugs for
                          initial and subsequent treatment regimens are
                          obtained by clinician prescription.] At
                          Months 1 and 4 and then every 4 months
                          thereafter, patients receive a physical
                          examination, and blood samples are drawn to
                          measure CD4 cell count and plasma HIV RNA
                          level. Changes in treatment regimens may
                          occur at any time, and reasons for the
                          changes are recorded.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Immunology, Viral
                          load.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 1410 patients. 370 [AS PER
                          AMENDMENT 5/30/00: to 470] patients per
                          treatment arm.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 1 year
                          [AS PER AMENDMENT 5/30/00: 2.5 to 3 years].
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1189/1410 010731.
PROTOCOL DETAILS          STUDY DURATION: 5 [AS PER AMENDMENT 5/30/00:
                          4 to 5] years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 17
PROTOCOL DETAILS          VERSION NUMBER & DATE: 3 (000530)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study; Open Label;
                          Random Allocation
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2.
                          Availability for at least 6 months of
                          treatment.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study Not pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded: Prior
                          exposure to antiretroviral therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Previous PI or
                          NNRTI use. 2. A cumulative total of more than
                          4 weeks of NRTI use (except 3TC) or more than
                          1 week of 3TC use.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Any
                          condition that, in the judgment of the
                          investigator, precludes successful
                          participation in the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0257  Abacavir sulfate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0043  Stavudine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0233  Indinavir sulfate
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0263  Nelfinavir mesylate
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 8  DRG-0269  Efavirenz
RESULTS                   Mannheimer S, Friedland G, Matts J, Child C,
                          Chesney M. 8th Conf Retro and Opportun
                          Infect. 2001 Feb 4-8 (abstract no. 485).
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral. Drug 4: Oral. Drug 5: Oral.
                          Drug 6: Oral. Drug 7: Oral. Drug 8: Oral
OTHER TREATMENT INFO.     END POINT: 1. Time to second study-defined
                          virologic failure following an initial
                          study-defined virologic failure associated
                          with a change in AR treatment regimen [AS PER
                          AMENDMENT 9/9/99: or death]. 2. Percentage of
                          individuals with plasma HIV RNA measurements
                          below the limit of detection (currently 50
                          copies/ml by the Roche ultrasensitive assay)
                          at the end of the study. 3. Number of plasma
                          HIV RNA levels above 2,000 copies/ml during
                          scheduled follow-up data collection visits.
                          4. Number of and reasons for changes in AR
                          treatment regimens.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Community Consortium / UCSF 3180 18th St /
                          Suite 201 San Francisco, CA 94110 Carroll
                          Child [phone] Recruiting 990408.
COLORADO                  Denver CPCRA / Denver Public Hlth 605 Bannock
                          St Denver, CO 802044507 Jack Rouff
                          [phone] Recruiting 990616.
CONNECTICUT               Yale Univ School of Medicine / AIDS Program
                          135 College St / Suite 323 New Haven, CT
                          06510 Laurie Andrews [phone] No longer
                          recruiting 010612.
DISTRICT OF COLUMBIA      Washington Reg AIDS Prog / Dept of Infect Dis
                          VA Med Ctr / 50 Irving St NW Washington, DC
                          20422 Barbara Standridge [phone]
                          Recruiting 990129.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon Ave / Suite 130 Atlanta, GA 303081962
                          Melanie Thompson MD [phone] No longer
                          recruiting 010528.
ILLINOIS                  AIDS Research Alliance - Chicago 2800 North
                          Sheridan Rd #108 Chicago, IL 60657 Rita
                          Verheggen [phone] Recruiting 990121.
LOUISIANA                 Louisiana Comm AIDS Rsch Prog / Tulane Univ
                          Med 1430 Tulane Ave / TB 21 New Orleans, LA
                          70112 Janice Walker [phone] Recruiting
                          990616.
MICHIGAN                  Henry Ford Hosp 2799 West Grand Blvd /
                          CFP-104 Detroit, MI 48202 Diane Mastro-Polak
                          [phone] Recruiting 990202.
MICHIGAN                  Wayne State Univ - WSU/DMC / Univ Hlth Ctr
                          4201 Saint Antoine / POD 7C Detroit, MI 48201
                          Jan Kosmyna [phone] Recruiting 990121.
NEW JERSEY                Southern New Jersey AIDS Cln Trials / Dept of
                          Med 3 Cooper Plaza / Suite 220 Camden, NJ
                          08103 Maryann LiVolsi [phone]
                          Recruiting 990616.
NEW JERSEY                North Jersey Community Research Initiative
                          393 Central Ave / Suite 301 Newark, NJ
                          071032842 Robert C Sawyer [phone]
                          Recruiting 990204.
NEW MEXICO                Partners in Research / New Mexico 915 Camino
                          de Salud NE Albuquerque, NM 87131 Cynthia
                          Nicholson [phone] Recruiting 990616.
NEW YORK                  Harlem AIDS Treatment Grp / Harlem Hosp Ctr
                          506 Lenox Ave / Rm 3101A New York, NY 10037
                          Luis Fuentes [phone] Recruiting 990218.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn St Portland, OR 97210 Norma Martinez
                          [phone] Recruiting 990616.
PENNSYLVANIA              Philadelphia FIGHT 1233 Locust St / 5th Floor
                          Philadelphia, PA 19107 Jane Shull
                          [phone] Recruiting 990325.
TEXAS                     Univ TX Health Science Ctr 6431 Fannin St
                          Houston, TX 77030 Hilda Cuervo [phone]
                          Recruiting 010118.
VIRGINIA                  Richmond AIDS Consortium / Div of Infect
                          Diseases PO Box 980049 Richmond, VA 232980049
                          Vinnie Mitchell [phone] Recruiting
                          990407.

124
UNIQUE IDENTIFIER         NIH/01081
PROTOCOL ID NUMBERS       CC 97 I-0189
PROTOCOL TITLE            Studies of Lymphocyte Kinetics Using
                          Bromodeoxyuridine.
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To develop a more complete
                          understanding of lymphocyte kinetics (rate of
                          replication, destruction, and effects of
                          therapy) in HIV-infected patients using
                          bromodeoxyuridine (BrDU) as a marker of
                          replication. To determine the safety of both
                          single and repeated infusions of BrDU in
                          patients.
GENERAL DESCRIPTION       RATIONALE: To understand the mechanism behind
                          immunodeficiency in HIV patients, it becomes
                          advantageous to quantitatively track
                          lymphocyte replication and destruction. In
                          this study, BrDU, an analog of thymidine, is
                          infused into patients and subsequently
                          incorporated into target cell DNA.
                          Measurements of BrDU in subpopulations of
                          cells will determine the rate of replication
                          of these cells.
GENERAL DESCRIPTION       METHODOLOGY: To understand the rate of
                          lymphocyte replication, patients are given a
                          30-minute infusion of BrDU. The BrDU is
                          incorporated into target cell DNA and then
                          used to track lymphocyte kinetics. Blood
                          samples are taken up to 12 times during the
                          day following the infusion. Subsequently,
                          blood may be drawn daily for the first week,
                          then twice weekly for an additional 3 weeks,
                          and then weekly to monthly for up to 1 year.
                          To obtain long-term safety information,
                          patients are seen or contacted by telephone
                          yearly for an additional 4 years. Patients
                          may later be asked to receive repeat
                          infusions. All patients are reimbursed for
                          time and potential discomfort.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug interactions, Drug safety,
                          Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 1 year with
                          subsequent follow-up by clinic or telephone
                          contact for 4 additional years.
PROTOCOL DETAILS          STUDY DURATION: 1 year with subsequent
                          follow-up for 4 additional years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Longitudinal Study
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: HIV infection, as documented by
                          ELISA/Western blot or, for acute
                          seroconverters, by PCR.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGOT(AST): < 300 IU (IU= international
                          units).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 300 IU.
PATIENT INCLUSION CRIT.   OTHER: For inclusion into study: < Grade 2
                          level toxicity for other laboratory values.
                          Neutrophils > 750 cells/mm3.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study Negative
                          pregnancy test.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Patients with active
                          substance abuse or prior history of substance
                          abuse that may interfere with protocol
                          compliance.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Therapy with
                          5-fluorouracil or cytokines (including IL-2).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Significant underlying cardiac, pulmonary,
                          renal, gastrointestinal, rheumatologies or
                          CNS disease as detectable on routine history,
                          physical exam, or screening laboratory
                          studies. 2. Psychiatric illness or
                          disturbance that, in the assessment of the
                          protocol team, may affect patient safety or
                          compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0309  Broxuridine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: 30-minute infusion
                          of 200 mg/m2
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: A single 30-minute
                          infusion.
OTHER TREATMENT INFO.     END POINT: Rate of lymphoctye replication and
                          destruction, safety of BrDU infusions.
OTHER TREATMENT INFO.     MODIFICATION: Dosages are modified for
                          toxicity management.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 991130.

125
UNIQUE IDENTIFIER         NIH/01077
PROTOCOL ID NUMBERS       NIAID ACTG 386
PROTOCOL TITLE            A Phase I Trial of the Safety and
                          Pharmacokinetics of Fortovase
                          (Saquinavir-SGC) Co-Administered with Low
                          Dose (Ritonavir) RTV, ZDV and 3TC in HIV
                          Seropositive Pregnant Women During Gestation
                          and Postpartum, and in Their Infant's
                          Post-Maternal Dosing.
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Pregnancy
PROTOCOL CHAIRS           CHAIR  Carmen Zorrilla
PROTOCOL CHAIRS           CO-CHAIR  Arlene Bardeguez
GENERAL DESCRIPTION       PURPOSE: To assess the antepartum and
                          postpartum pharmacokinetics, safety, and
                          tolerance of saquinavir-SGC (SQV) when
                          combined with [AS PER AMENDMENT 8/15/00:
                          ritonavir (RTV),] zidovudine (ZDV), and
                          lamivudine (3TC) in HIV-infected pregnant
                          women [AS PER AMENDMENT 8/15/00: and to
                          determine if SQV can achieve adequate drug
                          exposure during pregnancy with the addition
                          of low-dose RTV to SQV]. To assess the
                          transplacental passage of SQV and to
                          determine the safety and tolerance of prior
                          maternal dosing in the newborn.
GENERAL DESCRIPTION       RATIONALE: Although administration of ZDV to
                          mother-infant pairs has dramatically reduced
                          perinatal HIV infection, the goal is to
                          reduce it further to less than 2%. In order
                          to achieve this, combination strategies need
                          to be developed for 2 purposes: 1) to reduce
                          the perinatal transmission rate to goal
                          levels; and 2) to provide other combination
                          therapies for HIV-infected mothers whose
                          virus has become resistant to ZDV, who have a
                          very high viral load, or who have previously
                          transmitted HIV while on ZDV. This study adds
                          3TC (another reverse transcriptase inhibitor)
                          and SQV (a protease inhibitor [PI]) [AS PER
                          AMENDMENT 8/15/00: with low-dose RTV (another
                          PI)] to the mother's ZDV regimen.
GENERAL DESCRIPTION       METHODOLOGY: During the antepartum period,
                          mothers receive SQV with [AS PER AMENDMENT
                          8/15/00: low-dose RTV plus] ZDV and 3TC. At
                          onset of active labor, mothers receive
                          loading doses of each of the study drugs,
                          then receive study drugs for 12 weeks
                          postpartum on the same schedule as during the
                          antenatal period. Within 12 hours of
                          delivery, infants begin receiving 3TC and ZDV
                          and continue until 6 weeks of age. Mothers
                          are followed until 12 weeks postpartum and
                          babies are followed until 6 months of age.
                          [AS PER AMENDMENT 2/9/99: For maternal
                          dosing, 1 Combivir tablet (containing 3TC and
                          ZDV) may be administered in place of the
                          individual agents 3TC and ZDV. Patients who
                          prematurely discontinue study treatment
                          should continue to be followed for the
                          duration of the study.].
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety, Drug tolerance,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients. 10 evaluable
                          pregnant women and their infants.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Mothers: 6 to 9
                          months depending on the week of pregnancy in
                          which the mother enrolled in the study.
                          Infants: Up to age 6 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 19/24 010724.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 15
PROTOCOL DETAILS          VERSION NUMBER & DATE: 4 (000815)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 386
PROTOCOL DETAILS          STUDY DESIGN: Multicenter Study
INPATIENT/OUTPATIENT ST.  Both Inpatient and Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection, documented by ELISA
                          and confirmed by Western blot or other
                          confirmatory test. 2. Pregnancy [AS PER
                          AMENDMENT 2/9/99: with a single fetus] with a
                          gestational age of 14 to 32 weeks for
                          singleton pregnancy, or 14 to 30 weeks
                          gestation for twin pregnancies, based on
                          menstrual history and confirmed by an early
                          ultrasound. [AS PER AMENDMENT 2/9/99: Only
                          patients who are pregnant with a single fetus
                          (gestational age 14 to 32 weeks) are
                          eligible.] 3. Normal Level 2/targeted fetal
                          ultrasound. 4. Informed consent from patient
                          and/or guardian, including reasonable attempt
                          to gain such from the father of the fetus.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophil count >= 1,000
                          cells/mm3. Amylase <= ULN with normal lipase.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Pregnant.
PATIENT INCLUSION CRIT.   WEIGHT: Birth weight over 2 kg (4.4 pounds).
PATIENT INCLUSION CRIT.   PRIOR MEDICATION: Allowed: 1. Prior treatment
                          with didanosine (ddI), zalcitabine (ddC),
                          stavudine (d4T), or ZDV. [AS PER AMENDMENT
                          2/9/99: Less than 3 weeks of 3TC is also
                          allowed. Women currently receiving 3TC in
                          combination with ddI, ddC, d4T, or ZDV and
                          who have received 3TC for longer than 3 weeks
                          are eligible only if, over the prior 3
                          months, they have had a stable or increasing
                          CD4 count and their HIV RNA level has been
                          below 400 copies/ml (patients must be
                          discussed with protocol chair prior to
                          enrollment).] [2. AS PER AMENDMENT 8/15/00:
                          Women who have received less than 3 weeks of
                          SQV (with or without RTV) in combination with
                          ZDV and 3TC are eligible. Women switching
                          from 1 protease
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Allowed: 1.
                          Clarithromycin, phenobarbital, ketoconazole,
                          carbamazepine, erythromycin, phenytoin, and
                          itraconazole, with permission of protocol
                          chair. [2. AS PER AMENDMENT 8/15/00:
                          Antibiotics, acetaminophen, antihistamines
                          (except terfenadine and astemizole), prenatal
                          vitamins, antiemetics, iron, calcium,
                          selected antifungal agents, butorphanol,
                          morphine, and intravenous (IV) fentanyl (if
                          administered in a setting where careful
                          monitoring and intubation, if necessary, can
                          be accomplished immediately).] Allowed with
                          caution and to be prescribed only after
                          consulting with the protocol chair:
                          Rifabutin, midazolam, dihydropyridines
                          (primarily nicardipine, felodipine, and
                          isradipine), and nifedipine, miconazole,
                          ranitidine, cimetidine, fluconazole,
                          dexamethasone, nevirapine, estrogens,
                          ergotamine, cyclosporine, dapsone,
                          pyrazinamide, and quinidine.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 13
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following conditions are excluded: 1.
                          Intolerance of mother to ZDV or 3TC. [2. AS
                          PER AMENDMENT 8/15/00: Intolerance or allergy
                          of mother to RTV. Women who have experienced
                          gastrointestinal intolerance to RTV which was
                          believed to be dose related may tolerate low
                          dose (100 mg) used in this study and may be
                          considered for enrollment.] 3. Intrauterine
                          growth restriction less than the 3rd
                          percentile [AS PER AMENDMENT 2/9/99: less
                          than the 10th percentile] for gestational age
                          by ultrasound. 4. Pre-entry
                          ultrasound-diagnosed major fetal anomaly that
                          is incompatible with life or that will
                          interfere with conduct of the study. 5.
                          Abnormal amniotic fluid on entry, e.g.,
                          polyhydramnios (AFI greater than 20 cm) or
                          oligohydramnios (AFI greater than 5 cm). 6.
                          Triplet or higher multiple gestation
                          pregnancy. [AS PER AMENDMENT 2/9/99: Twin
                          pregnancy excluded.] [AS PER AMENDMENT
                          2/9/99: The following additional criteria are
                          added to exclude women with risk factors for
                          premature birth or poor infant outcome: 7.
                          Poor obstetrical history including
                          spontaneous abortions (3 or more), prior
                          pre-term (less than
PATIENT EXCLUSION CRIT.   WEIGHT: Birth weight under 2 kg.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Current use of
                          illicit substance or alcohol abuse. [AS PER
                          AMENDMENT 2/9/99: Methadone allowed.].
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Participation
                          during current pregnancy in any other
                          therapeutic or vaccine perinatal treatment
                          trial.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          treatment with SQV. Previous treatment with
                          other protease inhibitors may be allowed if
                          approved by protocol chair. [AS PER AMENDMENT
                          8/15/00: Women who have received less than 3
                          weeks of SQV (with or without RTV) in
                          combination with ZDV and 3TC are eligible.
                          Women switching from 1 protease inhibitor to
                          SQV (with or without RTV) and women who have
                          been on other nucleoside reverse
                          transcriptase inhibitors (ddI and d4T) and
                          switch to ZDV and 3TC are also eligible as
                          long as it is within the 3-week time frame.
                          Women currently on SQV (with or without RTV),
                          3TC, and ZDV for longer than 3 weeks are
                          eligible only if, in the 3 months prior to
                          enrollment, CD4 counts are stable or
                          increasing and HIV RNA PCR is below 400
                          copies/ml.] 2. 3TC treatment prior to
                          pregnancy or for more than 3 weeks during
                          pregnancy. (See exceptions noted above.) 3.
                          Nonnucleoside reverse transcriptase
                          inhibitors in the 3 weeks prior to study. 4.
                          Ongoing or anticipated need for medica
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral therapy except SQV, 3TC, ZDV
                          [AS PER AMENDMENT 8/15/00: and RTV]. 2.
                          Anticancer chemotherapeutic agents. 3.
                          Rifampin, terfenadine, astemizole, cisapride,
                          and triazolam. 4. Medications with
                          significant interaction with SQV [AS PER
                          AMENDMENT 8/15/00: or other study
                          medications]. [5. AS PER AMENDMENT 2/9/99:
                          Systemic and inhaled steroids.] [AS PER
                          AMENDMENT 8/15/00: Chronic systemic and
                          inhaled steroids.] [6. AS PER AMENDMENT
                          8/15/00: IV fentanyl, unless administered in
                          a setting where careful monitoring and
                          intubation, if necessary, can be accomplished
                          immediately. Excluded for patients taking
                          ritonavir: Alprazolam, amiodarone, anticancer
                          agents, astemizole, bepridil, bupropion,
                          cisapride, clorazepate, clozapine,
                          cyclosporine, diazepam, disopyramide
                          phosphate, encainide hydrochloride,
                          ergotamine tartrate, estazolam, flecainide
                          acetate, flurazepam hydrochloride, indinavir,
                          meperidine hydrochloride, metronidazole,
                          midazolam hydrochloride,
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active opportunistic infection and/or serious
                          bacterial infection at time of entry. 2.
                          Chronic malabsorption or chronic diarrhea.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0164  Saquinavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0244  Ritonavir
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Maternal: 1,200 mg
                          tid until active labor and postpartuonset of
                          labor, 1,200 mg loading dose po, then 1,200
                          mg tid if exceeds 8 hours. [AS PER AMENDMENT
                          8/15/00: Maternal: 800 mg bid until active
                          labor and for 12 weeks postpartum; at oof
                          labor, 800 mg loading dose and if labor
                          exceeds 12 hours, 80q 12 hours until cord is
                          clamped.] Drug 2: Maternal: 150 mg bid until
                          active labor and for 12 weekpostpartum
                          beginning after cord is clamped; at onset of
                          labor, mg loading dose and if labor exceeds
                          12 hours, 150 mg q 12 hours until corclamped.
                          Infant: 2.0 mg/kg bid for 6 weeks. Drug 3:
                          Maternal: 200 mg po tid until active labor
                          and for 12 wpostpartum beginning after cord
                          is clamped; at onset of labor, mg/kg loading
                          dose IV over 1 hour, then 1.0 mg/kg per hour
                          IV until cord is clamped. Infant: 2.6 mg/kg
                          po tid for 6 weeks or 2.0 mg/kg IV tid for 6
                          if unable to tolerate po ZDV. Drug 4: [AS PER
                          AMENDMENT 8/15/00: Maternal: 100 mg bid until
                          alabor and for 12 weeks postpartum beginning
                          after cord is clampat onset of labor, 100 mg
                          loading dose and if labor exceeds 12 hours,
                          100 mg bid until cord is clamped.]
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 2: Infant: 4.0 mg/kg. Drug
                          4: [AS PER AMENDMENT 8/15/00: 200 mg.]
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral Drug 2: Oral Drug
                          3: Oral or IV. Drug 4: [AS PER AMENDMENT
                          8/15/00: Oral]
OTHER TREATMENT INFO.     TREATMENT DURATION: Mothers: 6 to 9 months
                          depending on the week of pregnancy in which
                          the mother enrolled in the study. Infants: Up
                          to age 6 months.
OTHER TREATMENT INFO.     END POINT: Safety, tolerance,
                          pharmacokinetics, viral load, immunologic
                          markers.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Patient or
                          legal guardian refuses further treatment or
                          follow-up evaluations (for mother and
                          infant). 2. Investigator determines that
                          further participation would be detrimental to
                          patient's health or well-being (for mother
                          and infant). 3. Failure to comply with study
                          requirements so as to cause harm to self or
                          seriously interfere with validity of study
                          results. 4. Unacceptable toxicity for mother
                          and infant. [5. AS PER AMENDMENT 8/15/00: If
                          the dose of SQV is increased to a higher
                          level based on failure to achieve target area
                          under the concentration time curve (AUC) and
                          AUC remains below target after 2 weeks on
                          higher dose, the patient will come off drug
                          on study and be offered the best available
                          therapy prescribed by the patient's
                          physician.] Treatment is discontinued for
                          infants only for the following reasons: 1.
                          Inability to tolerate oral medications for
                          over 72 hours. 2. Severe congenital
                          malformation or other conditions incompatible
                          with life. 3. Severe anemia, hypovolemia, or
                          hyperbilirubinemia requiring volume
                          replacement or blood product therapy. 4.
                          Documented or suspected serious infectious,
                          cardiac, respiratory, or metabolic illness,
                          or other immediate life-threatening
                          conditions. 5. Born of mothers who
                          discontinued treatment prior to delivery. 6.
                          Requirement for treatment with medications
                          that are disallowed on study.
OTHER TREATMENT INFO.     MODIFICATION: [AS PER AMENDMENT 8/15/00: If
                          SQV target (area under the concentration time
                          curve [AUC] greater than 10,000 ng x h/ml) is
                          not achieved by an individual patient after 2
                          weeks of compliance with study therapy or if
                          the SQV target is not achieved by the first 6
                          patients, then doses are increased from 800
                          mg to 1200 mg.].
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
CALIFORNIA                Los Angeles County - USC Med Ctr 1640 Marengo
                          St Los Angeles, CA 90033 Eva Operskalski
                          [phone] Recruiting 010124.
COLORADO                  Univ of Colorado Health Sciences Ctr 4200
                          East 9th Ave / Colorado ACTU / Campus Box
                          B-196 Denver, CO 80262 M Graham Ray
                          [phone] Recruiting 000926.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 000926.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 000926.
FLORIDA                   Univ of Miami / Jackson Memorial Hosp 1500
                          Northwest 12th Ave / 8th Floor Miami, FL
                          33136 Patricia Bryan [phone] Recruiting
                          000926.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] No longer
                          recruiting 010528.
LOUISIANA                 Univ Hosp 2021 Perdido St New Orleans, LA
                          70112 Kim Anglin [phone] Recruiting
                          000926.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 000926.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 000926.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 000926.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 000926.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 000926.
OTHER                     Univ of Puerto Rico / Univ Children's Hosp
                          AIDS GPO Box 365067 San Juan, PR 009365067
                          Carmen Rivera [phone] Recruiting
                          000926.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone]
                          Recruiting 000926.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 000926.

126
UNIQUE IDENTIFIER         NIH/01049
PROTOCOL ID NUMBERS       NIAID ACTG 367
PROTOCOL TITLE            Medical Chart Abstraction of HIV-Infected
                          Pregnant Women and Their Infants Receiving
                          Care or Consultation at Study Sites.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Pregnancy
TRIAL CATEGORY            Adult
PROTOCOL CHAIRS           CHAIR  Ruth Tuomala
PROTOCOL CHAIRS           CO-CHAIR  Renee Samelson
GENERAL DESCRIPTION       PURPOSE: To determine the clinical
                          characteristics and numbers of HIV-infected
                          pregnant women available for participation in
                          Pediatric ACTG perinatal trials. To determine
                          the antiretroviral usage patterns among these
                          women during both the immediate pre-pregnancy
                          period and during pregnancy. To describe the
                          characteristics relevant to the
                          inclusion/exclusion criteria in proposed
                          perinatal trials in order to assist with
                          accrual estimates for future trials.
GENERAL DESCRIPTION       RATIONALE: The population served at
                          affiliated ACTG sites has not been officially
                          described. Anecdotal evidence, however, has
                          surfaced regarding the characteristics of
                          HIV-infected pregnant women and the current
                          standard of care during pregnancy. This chart
                          abstraction study is designed to define, more
                          accurately, the pertinent characteristics and
                          general numbers of women in these trials.
GENERAL DESCRIPTION       METHODOLOGY: In this medical chart
                          abstraction study, pertinent information is
                          collected on all HIV-infected pregnant women
                          and their infants who receive primary or
                          consultative care at PACTG 367 study sites.
                          Part A profiles all HIV-infected women who
                          received care or consultation at study sites
                          and who had a pregnancy outcome between
                          January 1, 1998 through July 1, 1998. Part B
                          profiles HIV-infected pregnant women who
                          receive primary or consultative care and a
                          pregnancy outcome following July 1, 1998.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010726)
PROTOCOL DETAILS          STUDY INTENT: Epidemiology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 2000 patients. 500 on part
                          A and 1000 on part B.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 3418/2000 010731.
PROTOCOL DETAILS          STUDY DURATION: Initial accrual 1 year, then
                          based on assessed value and data.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 65
PROTOCOL DETAILS          VERSION NUMBER & DATE: 1 (980721)
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          OTHER PROTOCOL NUMBERS: PACTG 367
PROTOCOL DETAILS          STUDY DESIGN: Retrospective Study
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Maternal: 1. Evidence of HIV-1
                          infection (documented by ELISA and confirmed
                          by Western blot), or a positive HIV viral
                          detection test (by culture or PCR). 2.
                          Primary or consultative care at a study site
                          during study period. Infants: Born to study
                          mothers.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   OTHER: Included: Male and female infants and
                          their mothers. This study is approved for
                          prisoner participation.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to N/A
                          less than or equal to N/A.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Adult males.
OTHER TREATMENT INFO.     END POINT: Availability for perinatal trials,
                          antiretroviral usage, characteristics
                          pertinent to inclusion/exclusion criteria of
                          current and future perinatal trials.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010726
ALABAMA                   Univ of Alabama at Birmingham - Pediatric
                          1600 7th Ave South Birmingham, AL 35233
                          Gloria Hughes [phone] Recruiting
                          990917.
ALABAMA                   Univ of South Alabama 1504 Springhill Avenue
                          Mobile, AL 36604 Julie Bebawy [phone]
                          Recruiting 000801.
ARIZONA                   Phoenix Childrens Hosp 909 East Brill Street
                          Phoenix, AZ 85006 Judith O'Haver
                          [phone] Recruiting 990917.
CALIFORNIA                Harbor - UCLA Med Ctr / UCLA School of
                          Medicine 1000 West Carson Blvd Los Angeles,
                          CA 905022004 Zane O'Keefe [phone]
                          Recruiting 981217.
CALIFORNIA                UCSF / Moffitt Hosp - Pediatric 505 Parnassus
                          Ave San Francisco, CA 941430105 Debbie
                          Trevithick [phone] Recruiting 981022.
CALIFORNIA                San Francisco Gen Hosp 1001 Potrero Ave /
                          Ward 6 / D-4 San Francisco, CA 94110 Kelly
                          Slaven [phone] Recruiting 981022.
CALIFORNIA                Los Angeles County - USC Med Ctr 1929 Zonal
                          Ave / Health Science Campus (CAB-HSC) Los
                          Angeles, CA 90033 Andrea Kovacs [phone]
                          Recruiting 981123.
CALIFORNIA                Long Beach Mem UCLA School of Med / 10833 Le
                          Conte Ave Los Angeles, CA 900951752 Zane
                          O'Keefe [phone] Recruiting 991015.
CALIFORNIA                UCLA Med Ctr / Pediatric 10833 Le Conte Ave
                          Los Angeles, CA 900951752 Zane OKeefe
                          [phone] Recruiting 990601.
COLORADO                  Children's Hosp of Denver 1056 East 19th Ave
                          / B-055 Denver, CO 802181088 Carol
                          Salbenblatt [phone] Recruiting 990917.
CONNECTICUT               Univ of Connecticut / Farmington 263
                          Farmington Ave Farmington, CT 06032 Gail
                          Karas [phone] Recruiting 990113.
CONNECTICUT               Connecticut Children's Med Ctr 263 Farmington
                          Ave Farmington, CT 060303805 Gail Karas
                          [phone] Recruiting 990917.
CONNECTICUT               Yale Univ Med School 20 York St / Pediatric
                          AIDS Care Program New Haven, CT 06504 Donna
                          Schroeder [phone] Recruiting 980917.
DISTRICT OF COLUMBIA      Children's Hosp of Washington DC 111 Michigan
                          Ave NW Washington, DC 200102916 Julie Ziegler
                          [phone] Recruiting 001110.
DISTRICT OF COLUMBIA      Washington Hosp Ctr 110 Irving St NW
                          Washington, DC 200102931 Rene Smit
                          [phone] Recruiting 001019.
DISTRICT OF COLUMBIA      Howard Univ Hosp 2041 Georgia Ave NW
                          Washington, DC 20060 Helga Finke
                          [phone] Recruiting 981210.
FLORIDA                   Univ of Miami (Pediatric) Jackson Memorial
                          Hospital / 1400 NW 10th Avenue Miami, FL
                          33161 Charlotte Goldberg [phone]
                          Recruiting 980928.
FLORIDA                   Univ of Miami / Jackson Memorial Hosp 1500
                          Northwest 12th Ave / 8th Floor Miami, FL
                          33136 Patricia Bryan [phone] Recruiting
                          980928.
FLORIDA                   North Broward Hosp District 417 South Andrews
                          Ave Fort Lauderdale, FL 33311 Pamela Munger
                          [phone] Recruiting 990917.
FLORIDA                   Univ of Florida Health Science Ctr /
                          Pediatrics 653-1 West 8th St Jacksonville, FL
                          32209 Michelle Eagle [phone] Recruiting
                          990917.
GEORGIA                   The Med Ctr Inc 710 Center St Columbus, GA
                          31901 Dawn Barnes [phone] Recruiting
                          990917.
GEORGIA                   Med College of Georgia 1120 15th St / Dept of
                          Pediatrics / HF 1135 Augusta, GA 30912 Teresa
                          Horne [phone] Recruiting 990917.
GEORGIA                   Emory Univ Hosp / Pediatrics 341 Ponce de
                          Leon Ave Atlanta, GA 30306 Renata Dennis
                          [phone] Recruiting 981119.
ILLINOIS                  Chicago Children's Memorial Hosp 2300
                          Children's Plaza / PO Box 155 Chicago, IL
                          606143394 Debbie Fonken-Cloutier
                          [phone] Recruiting 990723.
ILLINOIS                  Univ of Chicago Children's Hosp 5841 South
                          Maryland Ave / MC 6054 Chicago, IL 606371470
                          Pamela Lofton [phone] Recruiting
                          981105.
ILLINOIS                  Univ of Illinois College of Medicine /
                          Pediatrics 840 South Wood St Chicago, IL
                          60612 Julia Camacho [phone] Recruiting
                          990917.
ILLINOIS                  Cook County Hosp 2020 West Harrison St
                          Chicago, IL 60612 Cynthia Booth [phone]
                          Recruiting 991022.
LOUISIANA                 Univ Hosp 2021 Perdido St New Orleans, LA
                          70112 Kim Anglin [phone] Recruiting
                          990218.
LOUISIANA                 Tulane Univ / Charity Hosp of New Orleans
                          1430 Tulane Ave / Pediatric AIDS Clinical
                          Trials Unit New Orleans, LA 701122699 Kim
                          Anglin [phone] Recruiting 981009.
MASSACHUSETTS             Brigham and Women's Hosp 75 Francis St /
                          Children's Hosp AIDS Program Boston, MA 02115
                          Arlene Buck [phone] Recruiting 981215.
MASSACHUSETTS             Univ of Massachusetts Med School 55 Lake Ave
                          North Worcester, MA 016550001 Donna Christian
                          [phone] Recruiting 980923.
MASSACHUSETTS             Baystate Med Ctr of Springfield 759 Chestnut
                          St / SHU-Main 3 Springfield, MA 01199 MariPat
                          Toye [phone] Recruiting 981022.
MARYLAND                  Johns Hopkins Hosp - Pediatric 600 North
                          Wolfe St / Park 2-257 Baltimore, MD 212874933
                          Suzanne Marvin [phone] Recruiting
                          010723.
MICHIGAN                  Children's Hosp of Michigan 3901 Beaubien
                          Blvd Detroit, MI 48201 Charnell Cromer
                          [phone] Recruiting 981204.
MISSOURI                  Washington Univ School of Medicine One
                          Childrens Place St Louis, MO 63110 Phyllis
                          Ballard [phone] Recruiting 000317.
MISSISSIPPI               Univ of Mississippi Med Ctr 350 West Woodrow
                          Wilson Jackson, MS 39213 Sondra Sadler
                          [phone] Recruiting 981119.
NORTH CAROLINA            Univ of North Carolina at Chapel Hill / Duke
                          Univ Med Ctr PO Box 3499 Durham, NC 27710
                          John Swetnam [phone] Recruiting 990330.
NORTH CAROLINA            Duke Univ Med Ctr PO Box 3499 Durham, NC
                          277103499 John Swetnam [phone]
                          Recruiting 980923.
NEW JERSEY                St Peter's Med Ctr 254 Easton Ave New
                          Brunswick, NJ 08903 Marian Lake [phone]
                          Recruiting 010119.
NEW JERSEY                Univ of Medicine & Dentistry of New Jersey /
                          Univ Hosp 185 South Orange Ave / HIV/AIDS
                          Clinical Trials Newark, NJ 071032714 Mary Jo
                          Hoyt [phone] Recruiting 990119.
NEW YORK                  Harlem Hosp Ctr 506 Lenox Ave / Room 16-119
                          New York, NY 10037 Delia Calo [phone]
                          Recruiting 000419.
NEW YORK                  Metropolitan Hosp Ctr 1901 First Ave / Room
                          523 New York, NY 10029 Karen Novita
                          [phone] Recruiting 990402.
NEW YORK                  Columbia Presbyterian Med Ctr 622 West 168th
                          St New York, NY 10032 Marie Donahue
                          [phone] Recruiting 981119.
NEW YORK                  Bronx Lebanon Hosp Ctr 1650 Selwyn Ave /
                          Milstein Building / Room 2C Bronx, NY 10457
                          Wanda Biernick [phone] Recruiting
                          981001.
NEW YORK                  Children's Hosp at Albany Med Ctr 47 New
                          Scotland Ave / A-111 Albany, NY 12208 Mary
                          Ellen Adams [phone] Recruiting 980225.
NEW YORK                  State Univ of New York at Stony Brook Health
                          Sciences Ctr / 11th Floor Room 031 Stony
                          Brook, NY 117948111 Michell Davi
                          [phone] Recruiting 981224.
NEW YORK                  Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400
                          Pelham Parkway South Bronx, NY 10461 Wanda
                          Biernick [phone] Recruiting 001013.
NEW YORK                  Univ of Rochester Med Ctr 601 Elmwood Ave /
                          Box 690 Rochester, NY 146420001 Barbra
                          Murante [phone] Recruiting 990224.
NEW YORK                  Schneider Children's Hosp 269-01 76th Ave /
                          Room 235 New Hyde Park, NY 11040 Connie
                          Colter [phone] No longer recruiting
                          001110.
NEW YORK                  SUNY Health Sciences Ctr at Syracuse /
                          Pediatrics 750 East Adams St Syracuse, NY
                          13210 Kathie Contello [phone]
                          Recruiting 990917.
OHIO                      Columbus Children's Hosp 700 Children's Dr
                          Columbus, OH 432052696 Jane Hunkler
                          [phone] Recruiting 990809.
OTHER                     San Juan City Hosp Centro Medico / Mail
                          Station 128 / GPO Box 70344 San Juan, PR
                          009367344 Moraima Rivera [phone]
                          Recruiting 990916.
OTHER                     Ramon Ruiz Arnau Univ Hosp / Pediatrics
                          Laurel Ave Bayamon, PR 00956 Eva Reyes
                          [phone] Recruiting 981207.
PENNSYLVANIA              Temple Univ School of Medicine Erie Ave at
                          Front St Philadelphia, PA 191341095 Harold
                          Lischner [phone] Recruiting 001205.
PENNSYLVANIA              Thomas Jefferson Univ Hosp Jefferson Medical
                          College Dept of OB/GYN / 834 Chestnut St
                          Philadelphia, PA 191075098 Mary Talucci
                          [phone] Recruiting 010214.
SOUTH CAROLINA            Med Univ of South Carolina 171 Ashley Ave /
                          312 Clinical Science Building Charleston, SC
                          294253312 Barbara Stovall [phone]
                          Recruiting 980917.
TENNESSEE                 Methodist Hosp Central 332 North Lauderdale
                          Memphis, TN 381052794 Micki Roy [phone]
                          Recruiting 990917.
TENNESSEE                 Regional Med Ctr at Memphis 877 Jefferson Ave
                          / Room Ed15 Memphis, TN 38103 Micki Roy
                          [phone] Recruiting 990917.
TENNESSEE                 Saint Jude Children's Research Hosp of
                          Memphis 332 North Lauderdale Memphis, TN
                          381052794 Micki Roy [phone] Recruiting
                          980923.
TENNESSEE                 Vanderbilt Univ Med Ctr 1161 21st Ave South /
                          MCN D-7235 Nashville, TN 372322581 Peggy
                          Bender [phone] Recruiting 000310.
TEXAS                     Children's Med Ctr of Dallas 1935 Motor St
                          Dallas, TX 75235 Diane Ramirez [phone]
                          Recruiting 990707.
VIRGINIA                  Children's Hosp of the King's Daughters 601
                          Children's Lane Norfolk, VA 23507 Donna
                          Sandifer [phone] Recruiting 001031.
VIRGINIA                  Med College of Virginia Division of
                          Infectious Diseases / 1001 E Broad St Suite
                          LL25 Richmond, VA 23219 Tima Smith
                          [phone] Recruiting 990917.
VIRGINIA                  Senetara Norfolk Gen Hosp 601 Children's Lane
                          Norfolk, VA 23507 Donna Sandifer
                          [phone] Recruiting 001031.
WASHINGTON                Children's Hospital & Medical Center /
                          Seattle ACTU 4800 Sand Point Way NE Seattle,
                          WA 981050371 Kathleen Mohan [phone]
                          Recruiting 000728.

127
UNIQUE IDENTIFIER         NIH/01020
PROTOCOL ID NUMBERS       CC 97 I-0191
PROTOCOL TITLE            Studies of Lymphocyte Kinetics Using Stable
                          Isotopes.
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
GENERAL DESCRIPTION       PURPOSE: To evaluate the rate of lymphocyte
                          replication and destruction in HIV-1
                          seropositive and HIV-1 seronegative
                          volunteers who receive a continuous infusion
                          of [sigma,sigma-2H2]-glucose.
GENERAL DESCRIPTION       RATIONALE: This study examines lymphocyte
                          replication in both HIV-positive and healthy,
                          HIV-negative volunteers. It is believed that
                          an understanding of lymphocyte replication
                          will lead to greater knowledge of the
                          mechanisms responsible for HIV-induced
                          immunodeficiency.
GENERAL DESCRIPTION       METHODOLOGY: Up to 150 HIV-seropositive and
                          seronegative volunteers receive a
                          nonradioactive stable isotope of glucose
                          ([sigma,sigma-2H2]-glucose) as a continuous
                          IV for up to 5 days. A restricted diet is
                          required during the course of the infusion.
                          After treatment, volunteers are followed for
                          6 months. Volunteers are reimbursed for their
                          time and inconvenience.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          PROJECTED ACCRUAL: UP TO 150 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Open Label
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: HIV-positive
                          volunteers must have: HIV-1 seropositivity
                          documented by ELISA/Western blot or, for
                          acute seroconverters, by PCR. HIV-negative
                          volunteers must have: HIV-1 seronegativity
                          documented by ELISA/Western blot. All
                          volunteers must have: Adequate venous access
                          in arm for drawing blood on Day 5.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 10 g/dl.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not breast-feeding
                          Negative pregnancy test.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 18
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Volunteers with
                          the following prior conditions are excluded:
                          History of substance abuse that may affect
                          protocol compliance.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active substance
                          abuse or prior history of substance abuse
                          that may interfere with protocol compliance.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Volunteers with the following
                          symptoms or conditions are excluded: 1.
                          Active diabetes mellitus that requires drug
                          therapy. 2. Psychiatric illness or
                          disturbance that, in the judgment of the
                          assessment team, affects patient safety or
                          compliance. 3. Significant underlying
                          cardiac, pulmonary, renal, gastrointestinal,
                          rheumatologic, or CNS diseases that are
                          detectable on routine history, physical exam,
                          or screening laboratory studies.
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 5 days.
OTHER TREATMENT INFO.     END POINT: Lymphocyte replication.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 980527.

128
UNIQUE IDENTIFIER         NIH/01010
PROTOCOL ID NUMBERS       CC 98 I-0070
PROTOCOL TITLE            Magnetic Resonance Imaging of the Face and
                          Bones.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
GENERAL DESCRIPTION       PURPOSE: To determine whether magnetic
                          resonance imaging (MRI) can be used to
                          quantitate and follow facial wasting. To
                          investigate the potential entity of protease
                          inhibitor-associated lipodystrophy. To
                          determine if avascular necrosis of the hip
                          can be identified by MRI scans in
                          HIV-infected patients. Methodology: In this
                          minimal risk study, up to 350 patients and
                          volunteers receive MRI scans of the face. MRI
                          of the hip is performed on HIV-infected
                          patients.
GENERAL DESCRIPTION       METHODOLOGY: In this minimal risk study, up
                          to 350 patients and volunteers receive MRI
                          scans of the face. MRI of the hip is
                          performed on HIV-infected patients.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Natural history.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 350 patients. HIV-negative
                          volunteers will not be compensated.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 0/350.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Survey
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Volunteers must
                          have: 1. Likelihood of tolerating MRI without
                          sedation. (Note: Sedation is not provided by
                          protocol, and patients unable to tolerate the
                          procedure without sedation will not undergo
                          the procedure.) 2. Written informed consent
                          of a parent or guardian if under age 18.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study Not pregnant.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 04
                          years less than or equal to N/A.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Volunteers with
                          the following prior condition are excluded:
                          Intolerance of head MRIs (because of noise,
                          claustrophobia, etc.).
PATIENT EXCLUSION CRIT.   OTHER: Excluded: Current or prior employment
                          as a welder or metalworker.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Volunteers with the following
                          condition are excluded: Presence of cardiac
                          or neural pacemaker, aneurysm clip, cochlear
                          implant, metallic implant such as artificial
                          cardiac valve, or shrapnel.
SUPPORTING AGENCY         Natl Institute of Allergy and Infectious
                          Diseases.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting 991130.

129
UNIQUE IDENTIFIER         NIH/01009
PROTOCOL ID NUMBERS       CC 98 C-0041
PROTOCOL TITLE            A Pilot Study of the Immunologic
                          Reconstitution in HIV-1 Infected Children
                          Receiving Highly Active Antiretroviral
                          Therapy with Combination Ritonavir,
                          Nevirapine, and Stavudine.
TRIAL CATEGORY            Child
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Adolescent
TRIAL CATEGORY            Adult
TRIAL CATEGORY            Treatment Naive
GENERAL DESCRIPTION       PURPOSE: To determine whether the treatment
                          of HIV-infected children with highly active
                          antiretroviral therapy (HAART) with
                          ritonavir, nevirapine, and stavudine (d4T)
                          (with drug substitution in case of
                          intolerance) will effect immunoreconstitution
                          with repopulation of naive T-cells. To
                          determine the anti-HIV activity and the
                          safety of HAART therapy with ritonavir,
                          nevirapine, and d4T. To determine changes in
                          individual drug pharmacokinetic parameters
                          that result from HAART therapy; specifically,
                          ritonavir steady-state pharmacokinetics
                          before and after the addition of nevirapine,
                          and steady-state pharmacokinetic parameters
                          of nevirapine in combination with ritonavir
                          and d4T. To study the development of viral
                          resistance to the antiretroviral agents used
                          during therapy in a subset of patients and to
                          correlate the emergence of resistance with
                          virologic, immunologic, and clinical
                          parameters.
GENERAL DESCRIPTION       RATIONALE: A central question in AIDS
                          research is whether effective suppression of
                          HIV replication leads to regeneration of
                          T-cell populations with near-complete immune
                          reconstitution and normalization of the
                          cytokine profile without the requirement of
                          specific immunoreconstitutive therapy.
                          Although treatment of HIV-infected patients
                          results in increased CD4+ cell number, the
                          ability to regenerate the naive population of
                          CD4+ cells in adults remains unresolved.
                          Children have a greater underlying thymic
                          activity than adults, allowing researchers to
                          examine the potential for immune
                          reconstruction that can result from treatment
                          with effective antiretroviral therapy.
GENERAL DESCRIPTION       METHODOLOGY: Twenty-five HIV-infected
                          children (no greater than 18 years of age)
                          without prior treatment with protease
                          inhibitors, nevirapine, or stavudine are
                          entered on this pilot study. Patients are
                          stratified into 2 groups (at least 6
                          patients/group), based on severity of
                          clinical signs and symptoms and
                          immunosuppression, in accord with the CDC
                          1994 revised classification for HIV infection
                          in children less than 13 years of age and the
                          CDC 1993 revised HIV classification and
                          expanded AIDS surveillance definition for
                          adolescents and adults. All patients
                          initially receive oral combination therapy
                          with HAART (ritonavir, nevirapine, and
                          stavudine) for 24 months.
PROTOCOL PHASE            N/A
OPEN/CLOSED INDICATOR     Open (010725)
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug
                          interactions, Drug safety, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 25 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1
PROTOCOL DETAILS          DISEASE STUDIED: HIV Infections.
PROTOCOL DETAILS          STUDY DESIGN: Cohort Study
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Diagnosed HIV-1 infection as defined
                          by the Centers for Disease Control and
                          Prevention (CDC). No CDC categories N1, A1,
                          B1, and C1. 2. No active opportunisitic
                          infection (e.g., cytomegalovirus (CMV),
                          aspergillosis, cryptococcus, Candida.) 3. No
                          critical illness or clinical instability. 4.
                          Consent of parent or guardian if under age
                          18.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl Recent transfusion does
                          not exclude.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 /mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN ULN (Upper Limit of
                          Normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min.
PATIENT INCLUSION CRIT.   OTHER: WBC >= 1,500/mm3 OR ANC >= 750 mm3.
                          Serum amylase pancreatic isoenzyme < 90 U/L
                          (2 x adult ULN).
PATIENT INCLUSION CRIT.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
PATIENT INCLUSION CRIT.   CONCURRENT MEDICATION: Suggested drugs for
                          prophylaxis in the following conditions: 1.
                          Co-trimazole, pentamidine (aerosolized), and
                          dapsone for Pneumocystis carinii pneumonia
                          (PCP), when age-corrected absolute CD4 count
                          is < 200 cells/mm3, or CD4 percentage is <
                          15% at any point during participation in the
                          study. 2. Acyclovir for patients with a
                          history of recurrent herpes simplex or
                          varicella zoster virus infection. 3.
                          Clarithromycin or azithromycin for
                          Mycobacterium avium intracellulare (MAI)
                          prophylaxis, when age-corrected CD4 count is
                          < 125 cells/mm3. 4. Antibiotic prophylaxis
                          for asplenia, rheumatic fever, or cardiac
                          conditions warranting prophylaxis against
                          subacute bacterial endocarditis. 5. Patients
                          who develop opportunistic or acute childhood
                          infections during the trial may receive
                          appropriate systemic and suppressive therapy.
                          The protocol may be held for up to 8 weeks
                          due to the treatment of opportunistic
                          infections. 6. Investigational agents needed
                          by patients for the treatment or prophylaxis
                          of opportunistic infections are permissible
                          at the discretion of the princial
                          investigator and the chairperson.
PATIENT INCLUSION CRIT.   PATIENT AGE: Greater than or equal to 04
                          years less than or equal to 18 years.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of clinical pancreatitis AND/OR
                          history of elevated serum amylase pancreatic
                          isoenzyme of > 180 U/L. 2. History of
                          peripheral neuropathy >= grade 2.
PATIENT EXCLUSION CRIT.   WEIGHT: hdrawal and 7 ml/kg in a 6-week
                          period).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          treatment with ritonavir, indinavir,
                          nelfinavir, nevirapine, or stavudine. 2.
                          Administration of chemotherapeutic,
                          investigational, or immunomodulating agents
                          within 1 month of study enrollment (e.g.,
                          corticosteroids, interferons, pentoxifylline,
                          G-CSF/GM-CSF, erythropoietin, growth hormone,
                          or other growth factors).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          investigational antiretroviral agents. 2.
                          Antiretroviral agents not administered as a
                          part of the tested regimen. 3. Cytokines,
                          immunomodulatory agents, or other biological
                          response modifiers (e.g., erythropoietin,
                          G-CSF, GM-CSF, interferons, IL-2,
                          pentoxifylline, or growth hormone). 4.
                          Chemotherapeutic agents. 5. Systemic
                          corticosteroids other than those used for the
                          management of life-threatening complications
                          of HIV infection (e.g., Pneumocystis carinii
                          pneumonia and reactive airway disease). 6.
                          Concurrent zidovudine and stavudine. 7.
                          Excluded for patients receiving ritonavir:
                          Alprazolam, amiodarone, astemizole, bepridil,
                          bupropion, cisapride, clorazepate, clozapine,
                          diazepam, encainide, estazolam, flecainide,
                          flurazepam, meperidine, midazolam, piroxicam,
                          propafenone, propoxyphene, quinidine,
                          rifabutin, terfenadine, triazolam, and
                          zolpidem. 8. Excluded for patients receiving
                          nevirapine: Oral contraceptives,
                          ketoconazole, and rifampin. 9. Exc
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with any of the
                          following symptoms or conditions are
                          excluded: 1. Active opportunistic infection:
                          (e.g., cytomegalovirus [CMV], aspergillosis,
                          cryptococcus, Candida). 2. Critically ill or
                          unstable. 3. Inability to swallow tablets.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0244  Ritonavir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0043  Stavudine
OTHER TREATMENT INFO.     DOSAGE SCHEDULE: Drug 1: Pediatric: 250 mg/m2
                          q 12h on Day 1, 300 mg/m2 q 12h on2, 350
                          mg/m2 q 12h on Day 3, and 400 mg/m2 q 12h on
                          Day 4. Maxdose in children: 600 mg q 12h.
                          Adult: 300 mg bid on Day 1 then, 400 mg q 12h
                          on Days 2 and 3 500 mg q 12h on Day 4 then,
                          600 mg q 12h thereafter. Drug 2: Pediatric
                          (age 14 or younger) 120 mg/m2/day for 14
                          days120 mg/m2 q 12h. Adult (age 14 and older)
                          200 mg qd for 14 days then 200 mg q 12Drug 3:
                          Pediatric (age 2-16) 1 mg/kg/dose bid. Adult
                          (age 16 or older): 30 mg bid if less than 60
                          kg: 30 mg/dobid. 40 mg bid if 60 kg or more
OTHER TREATMENT INFO.     DAILY DOSAGE: Drug 1: Pediatric: 500 mg/m2 on
                          Day 1, 600 mg/m2 on Day 2, 700 on Day 3, and
                          800 mg/m2 on Day 4. Maximum dose in children:
                          1,mg. Adult: 600 mg on Day 1 then, 800 mg on
                          Days 2 and 3 then, 1,00on Day 4 then, 1,200
                          mg thereafter. Drug 2: Pediatric (age 14 or
                          younger) 120 mg/m2/day for 14 days120 mg/m2 q
                          12h. Adult (age 14 and older) 200 mg qd for
                          14 days then 200 mg q 12Drug 3: Pediatric
                          (age 2-16) 2 mg. Adult (age 16 or older): 60
                          mg if less than 60 kg: 30 mg/dose b80 mg if
                          60 kg or more
OTHER TREATMENT INFO.     DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     END POINT: Pharmacokinetics, safety,
                          efficacy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Grade 4
                          nonhematologic toxicity, regardless of
                          relationship to the study drug with toxicity.
                          2. Recurrence of grade 3 nonhematologic
                          toxicity or fever toxicity thought to result
                          from the antiviral drug regimen of ritonavir,
                          nevirapine, and stavudine and for whom there
                          is no suitable alternative anti-HIV drug
                          substitute available. 3. Recurrence of grade
                          3 nonhematologic or grade 4 hematologic or
                          fever toxicity attributed to the second
                          antiretroviral drug regimen. 4. Patient
                          elects to discontinues treatment. 5.
                          Infection that delays initiation or
                          resumption of antiretroviral treatment for >
                          8 weeks. 6. Evidence of progressive HIV
                          infection following treatment with >= 12
                          weeks of the initial or the second HAART
                          regimen. 7. Development of malignancy
                          requiring systemic therapy. 8. Pregnancy. 9.
                          Patient noncompliance resulting in
                          progressive HIV infection or that in the
                          opinion of the principal investigator or
                          chairperson substantially interferes with
                          data collection of the patient's medical
                          care. 10. Termination of study. 11. Medical
                          or psychiatric complications that in the
                          opinion of the principal investigator or
                          chairperson warrant discontinuation.
OTHER TREATMENT INFO.     MODIFICATION: Doses are modified for toxicity
                          management. In the event of continued
                          toxicity following temporary discontinuation
                          of nevirapine, ritonavir, or stavudine, the
                          following drugs may be substituted: 1.
                          Toxicity attributable to ritonavir: Replaced
                          with nelfinavir. 2. Toxicity attributable to
                          nevirapine: Replaced with lamivudine or
                          didanosine. 3. Toxicity attributable to
                          stavudine: Replaced with lamivudine,
                          didanosine, or zidovudine.
SUPPORTING AGENCY         Natl Cancer Institute.
LAST REVISION DATE        20010725
MARYLAND                  Warren G Magnuson Clinical Ctr Patient
                          Recruitment & Public Liaison Office / Bldg 61
                          Bethesda, MD 208924754 Patient Recruitment
                          [phone] Recruiting USA accrual 000620.

SS 2 /C?