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 (800)411-1222 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 (415)476-9296 Recruiting 980121. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 010517. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Barbara Longmire (919)966-7883 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 (518)262-6888 Recruiting 001006. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Ross Hewitt (716)898-4119 Recruiting 981028. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (504)584-3605 Recruiting 000907. LOUISIANA Earl K Long Early Intervention Clinic 1430 Tulane Ave TB-8 New Orleans, LA 70112 Kim Anglin (504)586-3804 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 (313)745-4450 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 (212)939-4045 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 (415)476-6480 Recruiting 980420. CALIFORNIA San Francisco Gen Hosp 1001 Potrero Ave / Ward 6 / D-4 San Francisco, CA 94110 Kelly Slaven (415)206-8919 Recruiting 980420. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 970918. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 000509. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 No longer recruiting 000127. MASSACHUSETTS Brigham and Women's Hosp 75 Francis St / Children's Hosp AIDS Program Boston, MA 02115 Arlene Buck (617)732-5452 Recruiting 980408. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 980527. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 990915. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 990915. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 No longer recruiting 991006. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 No longer recruiting 010410. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 980408. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 No longer recruiting 980730. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 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 (205)558-2328 Recruiting 970924. ALABAMA Univ of South Alabama 1504 Springhill Avenue Mobile, AL 36604 Julie Bebawy (334)405-5107 Recruiting 970919. ARIZONA Phoenix Childrens Hosp 909 East Brill Street Phoenix, AZ 85006 Judith O'Haver (602)239-5263 Recruiting 970919. CALIFORNIA Harbor - UCLA Med Ctr / UCLA School of Medicine 1000 West Carson Blvd Los Angeles, CA 905022004 Zane O'Keefe (310)206-6369 Recruiting 970919. CALIFORNIA Cedars Sinai / UCLA Med Ctr 8700 Beverly Boulevard Los Angeles, CA 900481804 Zane O'Keefe (310)206-6369 Recruiting 991102. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 970919. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 970919. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 Recruiting 970919. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 Recruiting 970919. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 971121. CONNECTICUT Connecticut Children's Med Ctr 263 Farmington Ave Farmington, CT 060303805 Gail Karas (860)679-2320 No longer recruiting 010123. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 Recruiting 970919. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 970919. FLORIDA Sacred Heart Children's Hosp / CMS of Florida 5192 Bayou Blvd Pensacola, FL 32503 Susan Wilson (850)484-5040 Recruiting 001024. FLORIDA Arnold Palmer Hosp for Children & Women 92 West Miller St Orlando, FL 32806 Kerry Mullen (407)841-5111 Recruiting 970919. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Brenda Haliburton-Jones (305)548-4445 Recruiting 980108. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 971106. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 970919. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 Recruiting 970919. FLORIDA Univ of South Florida One Davis Med Building / Suite 502 Tampa, FL 33606 Jennifer Lane (813)272-2582 Recruiting 970919. FLORIDA Univ of Miami / Jackson Memorial Hosp 1500 Northwest 12th Ave / 8th Floor Miami, FL 33136 Patricia Bryan (305)243-2154 Recruiting 980108. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 970919. GEORGIA The Med Ctr Inc 710 Center St Columbus, GA 31901 Dawn Barnes (706)571-1449 Recruiting 990915. GEORGIA Med College of Georgia 1120 15th St / Dept of Pediatrics / HF 1135 Augusta, GA 30912 Teresa Horne (706)721-2437 Recruiting 970919. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 Recruiting 970919. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 990119. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 Recruiting 970919. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 970919. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 971008. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 971003. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Sue Lovelace (410)706-8732 Recruiting 971003. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 Recruiting 970919. MISSOURI Washington Univ School of Medicine One Childrens Place St Louis, MO 63110 Phyllis Ballard (314)454-4145 Recruiting 980217. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 970919. NORTH CAROLINA Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr PO Box 3499 Durham, NC 27710 John Swetnam (919)684-6335 Recruiting 991227. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 Recruiting 970919. NEW JERSEY St Peter's Med Ctr 254 Easton Ave New Brunswick, NJ 08903 Marian Lake (732)745-8600 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 (973)972-3118 Recruiting 981203. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Silvia Callejas (732)235-7382 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 (973)972-3118 Recruiting 970919. NEW JERSEY Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl One Cooper Plaza Camden, NJ 08103 Mary Jo Hoyt (973)972-3118 Recruiting 000621. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 970919. NEW YORK SUNY - Brooklyn 450 Clarkson Ave / Box 49 Brooklyn, NY 11203 Denise Swindell (718)270-3185 Recruiting 980624. NEW YORK Cornell Univ Med College 1300 York Ave / PO Box 296 New York, NY 10021 Kathleen O'Keefe (212)746-3318 Recruiting 970919. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 971014. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 970919. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 971003. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 970919. NEW YORK Children's Hosp at Albany Med Ctr 47 New Scotland Ave / A-111 Albany, NY 12208 Mary Ellen Adams (518)262-6888 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 (516)444-1313 Recruiting 980504. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 971124. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 971021. OHIO Columbus Children's Hosp 700 Children's Dr Columbus, OH 432052696 Jane Hunkler (614)722-4460 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 (242)325-5120 Recruiting 010318. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 970923. OTHER Ponce Univ Hosp Immunology Clinic / Area Vieja / Carretera #14 Bo Machuelo Ponce, PR 00731 Betsy Ruiz (787)259-4771 Recruiting 970919. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 970919. OTHER Mayguez Med Ctr / Regional Immunology Clinic 410 Hostos Ave Mayguez, PR 00680 Carmen Montalvo (787)834-2110 Recruiting 980925. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 970919. OTHER Caguas Regional Hosp PO Box 5729 Caguas, PR 00726 Wanda Rivera (787)744-3141 No longer recruiting 001121. SOUTH CAROLINA Univ of South Carolina School of Med 4 Richland Med Park / Suite 203 Columbia, SC 29203 Alisa Lucas (803)434-7966 Recruiting 970919. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 No longer recruiting 010222. TEXAS Univ of Texas Health Sciences Ctr 7703 Floyd Curl Dr San Antonio, TX 78284 Rachel Davis (210)617-5111 Recruiting 970919. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 971009. TEXAS Children's Med Ctr of Dallas 1935 Motor St Dallas, TX 75235 Diane Ramirez (214)640-6198 Recruiting 980923. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 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 (206)528-5020 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 (310)206-6369 Recruiting 000817. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 000817. CALIFORNIA San Francisco Gen Hosp 1001 Potrero Ave / Ward 6 / D-4 San Francisco, CA 94110 Kelly Slaven (415)206-8919 Recruiting 000817. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 000817. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 No longer recruiting 010130. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 No longer recruiting 010115. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 000817. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 001013. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 000817. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 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 (773)257-6930 Recruiting 000824. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 000817. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 000817. LOUISIANA Univ Hosp 2021 Perdido St New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 000817. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000817. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 000817. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 000817. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 000817. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Sue Lovelace (410)706-8732 Recruiting 000817. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (516)444-1313 Recruiting 010424. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 000817. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 000817. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 000817. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 000817. PENNSYLVANIA Hosp of the Univ of Pennsylvania 3400 Spruce St / Maloney Building / 2nd Floor Philadelphia, PA 19104 Kathy Mooney (215)662-3253 Recruiting 000817. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (310)206-6369 Recruiting 990915. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 No longer recruiting 001121. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 970909. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 Recruiting 990629. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 980821. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 Recruiting 990915. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 001006. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 No longer recruiting 000829. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 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 (510)428-3885 Recruiting 990915. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 990915. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 970912. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 Recruiting 990629. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 970806. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 970806. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 No longer recruiting 000424. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 No longer recruiting 010123. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 970717. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 970725. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 No longer recruiting 010130. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 980204. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 990915. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 990915. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Sue Lovelace (410)706-8732 No longer recruiting 000829. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 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 (973)972-3118 Recruiting 970619. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 970617. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 980930. NEW YORK Cornell Univ Med College 1300 York Ave / PO Box 296 New York, NY 10021 Kathleen O'Keefe (212)746-3318 No longer recruiting 990203. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 970724. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 971003. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 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 (516)444-1313 Recruiting 010418. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 990719. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 No longer recruiting 010612. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 No longer recruiting 010717. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 990915. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 No longer recruiting 000817. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 970630. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 Recruiting 990723. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (800)411-1222 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 (800)411-1222 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 (205)558-2328 No longer recruiting 991210. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 980116. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 No longer recruiting 001213. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 Recruiting 980116. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 980116. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 No longer recruiting 010123. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 Recruiting 980116. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 No longer recruiting 000127. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 No longer recruiting 001121. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 980116. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 990716. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 980116. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 980116. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 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 (800)411-1222 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 (813)282-8544 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 (205)558-2328 Recruiting 991118. CALIFORNIA Children's Hosp of Los Angeles/UCLA Med Ctr 4650 Sunset Blvd Los Angeles, CA 900276016 Zane O'Keefe (310)206-6369 Recruiting 991118. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 991118. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 991118. CALIFORNIA UCLA Med Ctr / Pediatrics 10833 Le Conte Ave Los Angeles, CA 90095 Maryanne Dillon (310)206-6369 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 (323)343-8283 Recruiting 991118. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 991118. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 000509. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 Recruiting 991118. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 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 (303)372-5535 Recruiting 991118. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 Recruiting 991118. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Susan Zamer (202)884-2837 Recruiting 991118. FLORIDA Sacred Heart Children's Hosp / CMS of Florida 5192 Bayou Blvd Pensacola, FL 32503 Susan Wilson (850)484-5040 Recruiting 001019. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 000127. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 991118. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 991118. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 991118. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 991118. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000310. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 991118. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 991118. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 991118. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 991118. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Sue Lovelace (410)706-8732 Recruiting 991118. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 000524. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Lisa Cerrachio (732)235-7894 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 (973)972-3118 Recruiting 991118. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 000419. NEW YORK SUNY - Brooklyn 450 Clarkson Ave / Box 49 Brooklyn, NY 11203 Denise Swindell (718)270-3185 Recruiting 991118. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 991118. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 991118. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 010731. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 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 (212)241-0433 Recruiting 991118. NEW YORK Children's Hosp at Albany Med Ctr 47 New Scotland Ave / A-111 Albany, NY 12208 Mary Ellen Adams (518)262-6888 Recruiting 991118. NEW YORK New York Hosp - Cornell Med Ctr 505 East 70th St New York, NY 10021 Anne Monroe (212)746-3367 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 (516)444-1313 Recruiting 991118. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 991118. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 991118. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 991118. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 991118. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 Recruiting 000210. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (205)558-2328 No longer recruiting 010227. ALABAMA Univ of South Alabama 1504 Springhill Avenue Mobile, AL 36604 Julie Bebawy (334)405-5107 Recruiting 990915. CALIFORNIA Harbor - UCLA Med Ctr / UCLA School of Medicine 1000 West Carson Blvd Los Angeles, CA 905022004 Zane O'Keefe (310)206-6369 Recruiting 950516. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 950227. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 No longer recruiting 010501. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 950227. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 No longer recruiting 010115. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 No longer recruiting 001213. CALIFORNIA Children's Hosp of Los Angeles/UCLA Med Ctr 4650 Sunset Blvd Los Angeles, CA 900276016 Zane O'Keefe (310)206-6369 No longer recruiting 000928. CALIFORNIA Cedars Sinai / UCLA Med Ctr 8700 Beverly Boulevard Los Angeles, CA 900481804 Zane O'Keefe (310)206-6369 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 (323)226-5068 No longer recruiting 990712. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 No longer recruiting 010213. CONNECTICUT Univ of Connecticut / Farmington 263 Farmington Ave Farmington, CT 06032 Gail Karas (860)679-2320 No longer recruiting 010123. CONNECTICUT Connecticut Children's Med Ctr 263 Farmington Ave Farmington, CT 060303805 Gail Karas (860)679-2320 No longer recruiting 010123. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 No longer recruiting 960301. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 No longer recruiting 010712. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 950316. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 990915. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 961216. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 No longer recruiting 990805. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 Recruiting 990915. GEORGIA Med College of Georgia 1120 15th St / Dept of Pediatrics / HF 1135 Augusta, GA 30912 Teresa Horne (706)721-2437 Recruiting 990915. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 Recruiting 951130. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 950316. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 No longer recruiting 010116. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 Recruiting 950404. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 No longer recruiting 010518. LOUISIANA Earl K Long Early Intervention Clinic 1430 Tulane Ave TB-8 New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 990915. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 950303. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 No longer recruiting 000127. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 950524. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 950227. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 950801. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Sue Lovelace (410)706-8732 No longer recruiting 000829. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 No longer recruiting 010227. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 970212. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 950901. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Silvia Callejas (732)235-7382 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 (973)972-3118 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 (973)972-3118 No longer recruiting 010627. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 No longer recruiting 990805. NEW YORK SUNY - Brooklyn 450 Clarkson Ave / Box 49 Brooklyn, NY 11203 Denise Swindell (718)270-3185 Recruiting 950303. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 No longer recruiting 000228. NEW YORK Cornell Univ Med College 1300 York Ave / PO Box 296 New York, NY 10021 Kathleen O'Keefe (212)746-3318 No longer recruiting 990830. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Children's Hosp Pact Prog / Children's Hosp of Buffalo 239 Bryant St Buffalo, NY 14222 Debby Phillips (716)878-7245 No longer recruiting 960903. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 No longer recruiting 990805. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 No longer recruiting 991006. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 950405. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 No longer recruiting 000228. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 950227. NEW YORK Mount Sinai Med Ctr / Pediatrics One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 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 (518)262-6888 No longer recruiting 010313. NEW YORK Beth Israel Med Ctr / Pediatrics First Ave at 16th St New York, NY 10003 Ann Marshak (212)420-4432 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 (516)444-1313 Recruiting 950403. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 990915. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 No longer recruiting 010612. NEW YORK Montefiore Med Ctr Adolescent AIDS Program 111 East 210th St Bronx, NY 10467 Dina Monte (718)882-0023 Recruiting 950719. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 No longer recruiting 010501. OHIO Columbus Children's Hosp 700 Children's Dr Columbus, OH 432052696 Jane Hunkler (614)722-4460 Recruiting 990915. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 950717. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 No longer recruiting 010206. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 950717. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 No longer recruiting 991118. PENNSYLVANIA Saint Christopher's Hosp for Children Erie Ave at Front St Philadelphia, PA 191341095 Audrey Kamrin (215)427-5284 Recruiting 951213. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 No longer recruiting 991209. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 950410. TENNESSEE Vanderbilt Univ Med Ctr 1161 21st Ave South / MCN D-7235 Nashville, TN 372322581 Peggy Bender (615)322-2250 Recruiting 970829. TEXAS Hermann Hosp / Univ Texas Health Science Ctr 6410 Fannin St / Suite 720 Houston, TX 77030 Dr Marilyn Griffiths Doyle (713)794-4044 No longer recruiting 960410. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 950324. VIRGINIA Children's Hosp of the King's Daughters 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 No longer recruiting 010417. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 No longer recruiting 000621. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (800)411-1222 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 (205)558-2328 Recruiting 990826. ALABAMA Univ of South Alabama 1504 Springhill Avenue Mobile, AL 36604 Julie Bebawy (334)405-5107 Recruiting 990826. ARIZONA Phoenix Childrens Hosp 909 East Brill Street Phoenix, AZ 85006 Laura Clarke-Steffan (602)239-5261 Recruiting 001024. CALIFORNIA UCLA Med Ctr 10833 Le Conte Ave Los Angeles, CA 90095 Maryanne Dillon (310)206-6369 Recruiting 001024. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 930709. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 930824. CALIFORNIA San Francisco Gen Hosp 1001 Potrero Ave / Ward 6 / D-4 San Francisco, CA 94110 Maureen Shannon (415)206-3631 Recruiting 930824. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 930616. CALIFORNIA UCLA Med Ctr / Pediatrics 10833 Le Conte Ave Los Angeles, CA 90095 Maryanne Dillon (310)206-6369 No longer recruiting 010702. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 930609. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 Recruiting 930408. CALIFORNIA Children's Hosp of Los Angeles/UCLA Med Ctr 4650 Sunset Blvd Los Angeles, CA 900276016 Zane O'Keefe (310)206-6369 Recruiting 940627. CALIFORNIA Cedars Sinai / UCLA Med Ctr 8700 Beverly Boulevard Los Angeles, CA 900481804 Zane O'Keefe (310)206-6369 Recruiting 930802. CALIFORNIA Los Angeles County - USC Med Ctr 1640 Marengo St Los Angeles, CA 90033 Eva Operskalski (323)226-2342 Recruiting 001024. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 930430. CONNECTICUT Univ of Connecticut / Farmington 263 Farmington Ave Farmington, CT 06032 Gail Karas (860)679-2320 No longer recruiting 010130. CONNECTICUT Connecticut Children's Med Ctr 263 Farmington Ave Farmington, CT 060303805 Gail Karas (860)679-2320 Recruiting 990826. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 No longer recruiting 960301. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Julie Ziegler (202)884-4708 Recruiting 001024. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 930729. FLORIDA Sacred Heart Children's Hosp / CMS of Florida 5192 Bayou Blvd Pensacola, FL 32503 Susan Wilson (850)484-5040 Recruiting 001019. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 930514. FLORIDA Univ of Miami / Jackson Memorial Hosp 1500 Northwest 12th Ave / 8th Floor Miami, FL 33136 Patricia Bryan (305)243-2154 Recruiting 001024. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 970317. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 961216. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 950201. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 Recruiting 990826. GEORGIA The Med Ctr Inc 710 Center St Columbus, GA 31901 Dawn Barnes (706)571-1449 Recruiting 990826. GEORGIA Med College of Georgia 1120 15th St / Dept of Pediatrics / HF 1135 Augusta, GA 30912 Teresa Horne (706)721-2437 Recruiting 990826. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 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 (773)257-6930 Recruiting 001025. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 930520. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 940718. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 Recruiting 930910. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 990826. LOUISIANA Univ Hosp 2021 Perdido St New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 001025. LOUISIANA Earl K Long Early Intervention Clinic 1430 Tulane Ave TB-8 New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 990826. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 930831. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Bishop (617)355-8198 Recruiting 930802. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 940304. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 931213. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 930609. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Sue Lovelace (410)706-8732 Recruiting 940124. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 Recruiting 931118. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 970224. NORTH CAROLINA Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr PO Box 3499 Durham, NC 27710 John Swetnam (919)684-6335 Recruiting 990826. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 940304. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Lisa Cerrachio (732)235-7894 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 (973)972-3118 Recruiting 931227. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 930412. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 940815. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 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 (212)241-0433 Recruiting 990623. NEW YORK Children's Hosp at Albany Med Ctr 47 New Scotland Ave / A-111 Albany, NY 12208 Mary Ellen Adams (518)262-6888 Recruiting 930601. NEW YORK Beth Israel Med Ctr / Pediatrics First Ave at 16th St New York, NY 10003 Ann Marshak (212)420-4432 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 (516)444-1313 Recruiting 931013. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 990826. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 990826. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 930824. NEW YORK Montefiore Med Ctr Adolescent AIDS Program 111 East 210th St Bronx, NY 10467 Dina Monte (718)882-0023 Recruiting 990826. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 940405. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 931215. NEW YORK SUNY - Brooklyn 450 Clarkson Ave / Box 49 Brooklyn, NY 11203 Denise Swindell (718)270-3185 Recruiting 930402. NEW YORK Cornell Univ Med College 1300 York Ave / PO Box 296 New York, NY 10021 Kathleen O'Keefe (212)746-3318 Recruiting 940114. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 930830. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 Recruiting 930729. NEW YORK Montefiore Medical / AECOM 1300 Morris Park Ave Bronx, NY 19461 Gayle Kreinik (718)430-2940 Recruiting 010731. NEW YORK New York Hosp - Cornell Med Ctr 505 East 70th St New York, NY 10021 Anne Monroe (212)746-3367 Recruiting 001005. OHIO Columbus Children's Hosp 700 Children's Dr Columbus, OH 432052696 Jane Hunkler (614)722-4460 Recruiting 990826. OREGON Oregon Health Sciences Univ 3181 Southwest Sam Jackson Park Rd Portland, OR 97201 Toni Kempner (503)494-7943 Recruiting 010529. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 930514. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 930611. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 930402. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 931206. PENNSYLVANIA Saint Christopher's Hosp for Children Erie Ave at Front St Philadelphia, PA 191341095 Audrey Kamrin (215)427-5284 Recruiting 931216. RHODE ISLAND Rhode Island Hosp / Brown Univ 593 Eddy St Providence, RI 02903 Carolyn Dwyer (401)467-9884 No longer recruiting 960408. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Genny Connelly (803)792-2385 Recruiting 930520. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 930802. TENNESSEE Vanderbilt Univ Med Ctr 1161 21st Ave South / MCN D-7235 Nashville, TN 372322581 Peggy Bender (615)322-2250 Recruiting 000403. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 940706. TEXAS Children's Med Ctr of Dallas 1935 Motor St Dallas, TX 75235 Paula Luallen (214)456-6198 Recruiting 001024. VIRGINIA Children's Hosp of the King's Daughters 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 Recruiting 960426. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 Recruiting 970320. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (323)247-6430 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 (127)366-4532 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 (323)226-5068 Recruiting 010620. FLORIDA Univ of Miami PO Box 16960 Miami, FL 331016960 Amy Malmsberry (305)243-6362 Recruiting 010620. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 010620. NEW YORK St Luke's - Roosevelt Hosp Ctr 1111 Amsterdam Ave / 411 - Suite 2D New York, NY 10025 Robert Warford (212)523-6844 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 (516)444-1313 Recruiting 010620. NEW YORK New York Hosp / Cornell Med Ctr 525 East 68th St / Box 296 New York, NY 10021 Anne Monroe (212)746-3367 Recruiting 010620. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 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 (787)759-9595 Recruiting 010620. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 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 (312)572-4545 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 (212)263-6565 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 (212)327-7281 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 (716)275-5871 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 (212)305-0216 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 (212)305-3041 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 (212)305-4015 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 (415)476-9296 Recruiting 010413. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Patrick Milne (312)926-7873 Recruiting 010627. TEXAS Univ TX Med Branch 1012 Texas Ave / Graves Bldg Galveston, TX 77555 Suzanne Lanier (409)747-0218 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 (650)723-2804 Recruiting 010702. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010730. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 Recruiting 010723. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 010702. MISSOURI Washington Univ / St Louis Connect Care 4511 Forest Park Parkway / Suite 304 Saint Louis, MO 63108 Mike Klebert (314)454-0058 Recruiting 010712. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 010712. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 010618. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 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 (205)975-7925 Recruiting 010604. CALIFORNIA Univ of California San Francisco 3180 18th St San Francisco, CA 94110 Julieann Lewis (415)514-0550 No longer recruiting 010702. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 010627. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 010730. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010731. MISSOURI Washington Univ / St Louis Connect Care 4511 Forest Park Parkway / Suite 304 Saint Louis, MO 63108 Mike Klebert (314)454-0058 Recruiting 010621. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 010621. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010717. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010717. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 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 (323)343-8283 Recruiting 010621. COLORADO Denver Dept of Health and Hosps 4200 East 9th Ave / Campus Box B-196 Denver, CO 80262 M Graham Ray (303)372-5535 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 (303)372-5535 Recruiting 010702. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010618. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Ericka Patrick (404)616-6313 Recruiting 010618. HAWAII Queens Med Ctr Leahi Hospital / Young Building / 3675 Kilauea Ave Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010618. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010621. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 Recruiting 010621. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010618. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010618. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010712. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010712. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010712. LOUISIANA Charity Hosp / Tulane Univ Med School 1430 Tulane Ave SL-87 New Orleans, LA 70112 Mike Foster (504)584-1692 Recruiting 010628. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 010702. MISSOURI Washington Univ / St Louis Connect Care 4511 Forest Park Parkway / Suite 304 Saint Louis, MO 63108 Mike Klebert (314)454-0058 Recruiting 010618. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 010618. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010618. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 Recruiting 010627. NEBRASKA Univ of Nebraska Med Ctr 985130 Nebraska Med Ctr Omaha, NE 681985130 Frances Van Meter (402)559-8163 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 (212)263-6565 Recruiting 010618. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Rachele Cruz (716)898-3933 Recruiting 010618. NEW YORK Cornell Clinical Trials Unit 119 West 24th St / Ground Floor New York, NY 10011 Todd Stroberg (212)746-4178 Recruiting 010618. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010730. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Valery Hughes (212)746-4393 Recruiting 010618. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010618. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010618. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 010618. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 010731. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010731. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (973)972-3118 Recruiting 010605. NEW JERSEY St Joseph's Hosp & Med Center 703 Main St Paterson, NJ 07503 Anne Townley (973)754-2876 Recruiting 010705. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 010522. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Sylvia Davila Nieves (787)759-9595 Recruiting 010521. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Jill Utech (901)495-3490 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 (415)514-0550 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 (303)372-5535 Recruiting 010627. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010731. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 Recruiting 010612. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010605. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 010621. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 Recruiting 010517. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (205)558-2328 Recruiting 010605. CALIFORNIA Los Angeles County - USC Med Ctr 1640 Marengo St Los Angeles, CA 90033 Eva Operskalski (323)226-2342 Recruiting 010702. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Mary Caffery (619)543-8080 Recruiting 010730. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 010717. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Patricia Bryan (305)243-2154 Recruiting 010717. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 010712. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 010612. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 010605. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 010621. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Margaret Cowie (504)586-3804 Recruiting 010702. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Kirk Bertelsen (617)355-8189 Recruiting 010605. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 010621. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 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 (973)972-3118 Recruiting 010621. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 010605. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Caroline Nubel (718)960-1010 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 (516)444-1313 Recruiting 010702. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 010712. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 010730. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 010731. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Sylvia Davila Nieves (787)759-9595 Recruiting 010712. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 010712. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 010605. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 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 (800)411-1222 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 (800)411-1222 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 (602)307-5330 Recruiting 010420. ARIZONA Univ of British Columbia Department of Pharmacology and Therapeutics / 2176 Health ScienMall/Rm 305 Vancouver, BC Bobbi Zastre (604)642-6429 Recruiting 010420. CALIFORNIA Saint Francis Mem Hosp / HIV Care Unit 4th Floor / 900 Hyde St San Francisco, CA 94109 Karen Stonaker (415)353-6216 Recruiting 010420. CALIFORNIA Univ of Southern California SP21 Rand Schrader Clinic / 1300 N Mission Rd Rm 349 Los Angeles, CA 90033 Luis Mendez (323)343-8283 Recruiting 010420. DISTRICT OF COLUMBIA Dr Bruce Rashbaum Suite 401 / 2311 M St NW Washington, DC 20037 Alex Seymour (202)331-3888 Recruiting 010420. DISTRICT OF COLUMBIA Dupont Circle Physicians Group 1737 20th St NW Washington, DC 200091104 Linda Green (202)745-0201 Recruiting 010420. FLORIDA Associates in Research 3677 Central Ave / Suite D Fort Myers, FL 33901 Jaye Popoli (941)936-1700 Recruiting 010420. FLORIDA Steinhart Medical Associates 3659 South Miami Ave / Suite 4006 Miami, FL 33133 Amy Liebmann (305)856-2171 Recruiting 010420. FLORIDA Saint Josephs Comprehensive Research Institute 4200 N Armenia Ave / Suite 3 Tampa, FL 33607 Allis Emnett (813)870-4760 Recruiting 010420. FLORIDA North Broward Hosp District / HIV Clinical Research 1101 NW 1st St Fort Lauderdale, FL 33311 Elaine DiVeronica (954)467-3006 Recruiting 010420. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Ericka Patrick (404)616-6313 Recruiting 010420. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Jaci Imberger (312)572-4578 Recruiting 010420. KANSAS Univ of Kansas School of Medicine 1010 North Kansas St Wichita, KS 672143124 Janice Cerrulo (316)293-2617 Recruiting 010420. MICHIGAN Univ of Michigan Hospitals and Health Ctrs 3120 Taubman Ctr Ann Arbor, MI 481090378 Maggie Catoe (734)647-9830 Recruiting 010420. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 010420. NORTH CAROLINA Jemsek Clinic 16630 Northcross Dr / Suite 102 Huntersville, NC 28078 Paula Hutcherson (704)987-2111 Recruiting 010420. NORTH CAROLINA Duke Univ Med Ctr / Infectious Disease Clinic South Hosp Box 3306 / Trent Dr Durham, NC 27710 Meg McDaniel (919)668-0164 Recruiting 010420. NEBRASKA Univ of Nebraska Medical Ctr 985400 Nebraska Medical Ctr Omaha, NE 681985400 Michelle Brester (402)559-8621 Recruiting 010420. NEW JERSEY Robert Wood Johnson Med School/UMDNJ 1 Robert Wood Johnson Place New Brunswick, NJ 089030019 Tammy Hojeibane (732)235-8011 Recruiting 010420. NEW JERSEY ID Care Inc 411 Courtyard Dr Somerville, NJ 08876 Debbie Winters (908)725-2522 Recruiting 010420. NEW JERSEY UMDNJ - New Jersey Med School 185 South Orange Ave Newark, NJ 071032757 Carolyn Rogers (973)972-8700 Recruiting 010420. NEW MEXICO Univ of NM 915 Camino de Salud NE Albuquerque, NM 87131 Cynthia Nicholson (505)272-9390 Recruiting 010420. OHIO Ohio State Univ Hosp 456 West 10th Ave / Room 4725 Columbus, OH 432101282 Jane Russell (614)293-8112 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 (780)407-3333 Recruiting 010420. OTHER McMaster Univ Med Ctr 1200 Main Street West Hamilton , ON Lynn Kelleher (905)521-1200 Recruiting 010420. OTHER Gary Rubin 406-235 Danforth Ave Toronto, ON (416)463-6929 Recruiting 010420. OTHER Clinical Research Puerto Rico Inc 355 De Diego Ave San Juan, PR 009091711 Ana Campos (787)723-5945 Recruiting 010420. OTHER San Juan VAMC 10 Casia St San Juan, PR 009265800 Zydnia Pomales (787)641-7582 Recruiting 010420. PENNSYLVANIA Philadelphia FIGHT / Jay Kostman 1233 Locust St Philadelphia, PA 19107 Kelly Novitski (215)985-4448 Recruiting 010420. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Ann Arroyo (803)791-3983 Recruiting 010420. TENNESSEE Methodist Healthcare 1265 Union Avenue Memphis, TN 38104 Debra Terry (901)726-2268 Recruiting 010420. TEXAS Tarrant County Infectious Diseases Associates Suite 110 / 1325 Pennsylvania Ave Fort Worth, TX 76104 Tara Weaver (817)810-9810 Recruiting 010420. TEXAS Montrose Clinic 215 Westheimer Rd Houston, TX 77006 Mark Mall (713)830-3018 Recruiting 010420. TEXAS Oaklawn Physicians Group 3514 Cedar Springs Rd / Suite 200 Dallas, TX 75219 Gayle Trent (214)941-4000 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 (212)746-4435 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 (301)251-8351 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 (501)603-0003 Recruiting 010201. ARIZONA Phoenix Body Positive 1144 East McDowell Road Phoenix, AZ 85006 Linda Sirois (602)307-5330 Recruiting 010201. CALIFORNIA Orange County Ctr for Special Immunology 11190 Warner Ave / Suite 411 Fountain Valley, CA 92708 Sandy Cassarella (714)751-5800 Recruiting 010201. CALIFORNIA Pacific Horizons Med Group 2351 Clay St San Francisco, CA 94115 Jennifer Armfield (415)292-5477 Recruiting 010201. COLORADO Beacon Clinic / Boulder Community Hosp 1155 Alpine St Boulder, CO 80304 Anil Modak (303)938-3174 Recruiting 010201. DISTRICT OF COLUMBIA Georgetown Univ Med Ctr 3800 Reservoir Rd NW / 210 Kober-Cogan Building Washington, DC 20007 Scott Watson (202)687-1079 Recruiting 010201. DISTRICT OF COLUMBIA Dupont Circle Physicians Group 1737 20th St NW Washington, DC 200091104 Linda Green (202)745-0201 Recruiting 010201. FLORIDA Univ of Miami / Jackson Memorial Hosp 1500 Northwest 12th Ave / 8th Floor Miami, FL 33136 Christopher Kazubski (305)243-5621 Recruiting 010201. FLORIDA SBMA Research 333 41st St Miami Beach, FL 33140 Doreen Garabedian (305)534-1448 Recruiting 010201. FLORIDA Infectious Disease Consultants 685 Palm Springs Dr Altamonte Springs, FL 32701 Wendy Simmons (407)647-3960 Recruiting 010201. FLORIDA North Broward Hosp District / HIV Clinical Research 1101 NW 1st St Fort Lauderdale, FL 33311 Howard Yontef (954)467-3066 Recruiting 010201. GEORGIA Infectious Disease Specialists of Atlanta 2665 N Decatur Rd / Suite 330 Decatur, GA 30033 Katie McClure (404)297-9755 Recruiting 010201. ILLINOIS Northstar Med Clinic 2835 North Sheffield Ave Chicago, IL 60657 Tamara Hill (773)296-2400 Recruiting 010201. ILLINOIS Cook County Gen Hosp / Division of Infect Diseases 2020 West Harrison Chicago, IL 60612 Jo Ann Despotes (312)633-5655 Recruiting 010201. KENTUCKY University of Louisville / ID Division 511 S Floyd St Louisville, KY 40202 Jayne Carwile (502)852-1149 Recruiting 010201. LOUISIANA HIV Outpatient Clinics / LA State Univ Med Ctr 136 South Roman St New Orleans, LA 70112 Marsha Bennett (504)568-4732 Recruiting 010201. MASSACHUSETTS Boston Med Ctr 1 Boston Med Ctr Place / Dowling Bldg Boston, MA 02118 Sue Bazner (617)414-5404 Recruiting 010201. MICHIGAN Dr Paul Benson 2327 Coolidge Berkley, MI 48072 Dorothy Dempster (248)544-9300 Recruiting 010201. MINNESOTA Regions Hosp / HIV/AIDS Program 640 Jackson St / North Bldg St Paul, MN 55101 Jessica Kopaczewski (651)254-3589 Recruiting 010201. MINNESOTA Hennepin County Med Ctr 4th Floor N ID / Clinic #834 / 701 Park Ave Minneapolis, MN 55415 Marcia Meredith (612)347-7678 Recruiting 010628. MISSISSIPPI CRC of Mississippi 501 Marshall St Jackson, MS 39202 Kevin Kantor (601)714-3260 Recruiting 010201. NORTH CAROLINA ID Consultants 814 East Boulevard Charlotte, NC 28203 Leslie Climer (704)331-9413 Recruiting 010201. NORTH CAROLINA East Carolina Univ School of Medicine Section of Infectious Diseases 3E-117 / Brody Building Greenville, NC 27858 Grace Wilkins (252)816-1913 Recruiting 010201. NEW JERSEY Hackensack University Medical Center 20 Prospect St Hackensack, NJ 07601 Terry McKiernan (201)996-2378 Recruiting 010201. NEW JERSEY NJCRI 393 Central Ave / Suite 301 Newark, NJ 07103 Candace Tobin (973)483-3444 Recruiting 010201. NEVADA Wellness Ctr / Las Vegas 2300 South Rancho Blvd Las Vegas, NV 89102 Dennis Fuller (702)383-2691 Recruiting 010201. NEW YORK Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ 1230 York Ave New York, NY 10021 Arlene Hurley (212)327-7281 Recruiting 010201. NEW YORK SUNY / Health Sciences Ctr at Brooklyn 450 Clarkson Ave Brooklyn, NY 11203 Susan Holman (718)270-1069 Recruiting 010201. OHIO Summa Health System 75 Arch St Akron, OH 44304 Lisa Flood (330)375-3894 Recruiting 010201. OKLAHOMA Univ of Oklahoma Infectious Disease Institute 835 Stanton L Young Blvd Oklahoma, OK 73117 Brenda Hood (405)271-8001 Recruiting 010201. OKLAHOMA Associates in Med and Mental Health 2325 South Harvard / Suite 600 Tulsa, OK 74114 Marian Austin (918)743-1000 Recruiting 010201. TENNESSEE Univ of Tennessee Med Ctr at Knoxville 1924 Alcoa Hwy / Clinical Trials Research Prog Knoxville, TN 37920 Lacey Peltier (865)544-9356 Recruiting 010201. TEXAS Tarrant County Infectious Diseases Associates Suite 110 / 1325 Pennsylvania Ave Fort Worth, TX 76104 Tara Weaver (817)810-9810 Recruiting 010201. TEXAS Metroplex Infectious Disease 1350 South Main St Fort Worth, TX 76104 Michelle Bachman (817)877-3442 Recruiting 010201. TEXAS Diversified Med Practices PA 4126 Southwest Freeway Houston, TX 77027 Barbara Knight (713)961-7100 Recruiting 010201. TEXAS Therapeutic Concepts 1200 Binz / Suite 120 Houston, TX 77004 Marketer Washington (713)526-9821 Recruiting 010201. TEXAS Infectious Diseases Associates of Houston 6560 Fannin / Suite 1540 Houston, TX 77030 Joni Blais (713)799-9997 Recruiting 010201. TEXAS AIDS Outreach Center 801 West Cannon Fort Worth, TX 76104 Mickey Howell (817)335-1994 Recruiting 010201. TEXAS Texas Tech Health Sciences Ctr 4800 Alberta Ave El Paso, TX 79905 Rosy Sandoval (915)545-6626 Recruiting 010201. VIRGINIA Infectious Disease Consultants 10721 Main St Fairfax, VA 22030 Jan Calco (703)246-9563 Recruiting 010201. VIRGINIA Infectious Disease Physicians Inc 3289 Woodburn Rd Annandale, VA 22003 Myrna Burns (703)560-4821 Recruiting 010201. WASHINGTON Swedish Med Ctr 747 Broadway Seattle, WA 98122 Janice Price (206)386-6121 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 (323)783-8172 Recruiting 010529. CALIFORNIA Univ of California San Francisco 3180 18th St San Francisco, CA 94110 Julieann Lewis (415)514-0550 Recruiting 010406. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 010612. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 010702. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010522. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 010406. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Mario Guerrerro (310)222-3848 Recruiting 010423. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 010405. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010406. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Ericka Patrick (404)616-6313 Recruiting 010717. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010528. IOWA Univ of Iowa Hosp and Clinic 200 Hawkins Dr Iowa City, IA 52242 Julie Katseres (319)353-8441 Recruiting 010621. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010528. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010423. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010323. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010323. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010323. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 010418. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010423. NORTH CAROLINA Moses H Cone Memorial Hosp 1200 North Elm St Greensboro, NC 27401 Lisa Dasnoit (336)832-8062 Recruiting 010405. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 Recruiting 010323. NEBRASKA Univ of Nebraska Med Ctr 985130 Nebraska Med Ctr Omaha, NE 681985130 Frances Van Meter (402)559-8163 Recruiting 010314. NEW YORK St Mary's Hosp (Univ of Rochester/Infectious Diseases) 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 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 (212)263-6565 Recruiting 010502. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010423. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 010712. NEW YORK Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ 1230 York Ave New York, NY 10021 Arlene Hurley (212)327-7281 Recruiting 010323. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Rachele Cruz (716)898-3933 Recruiting 010502. NEW YORK Cornell Clinical Trials Unit 119 West 24th St / Ground Floor New York, NY 10011 Todd Stroberg (212)746-4178 Recruiting 010418. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 010318. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010418. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Valery Hughes (212)746-4393 Recruiting 010418. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010418. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010405. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 010502. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 010621. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 010508. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010702. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 010314. PENNSYLVANIA Philadelphia Veterans Administration Med Ctr 536 Johnson Pavilion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010605. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010405. RHODE ISLAND Brown Univ / Miriam Hosp 164 Summit Ave / Immunology Ctr Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010405. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 010405. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 010612. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Carrie Derkowski (409)747-0214 Recruiting 010628. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Chip Lohner (214)590-0414 Recruiting 010410. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (323)226-2342 Recruiting 010627. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 010419. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 010522. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 010522. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 010621. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 010419. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 010627. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Margaret Cowie (504)586-3804 Recruiting 010502. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Kirk Bertelsen (617)355-8189 Recruiting 010502. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 010502. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 010730. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 Recruiting 010522. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Lisa Cerrachio (732)235-7894 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 (973)972-3118 Recruiting 010419. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 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 (516)444-1313 Recruiting 010731. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 010419. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 010702. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 010517. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 010419. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Sylvia Davila Nieves (787)759-9595 Recruiting 010419. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Felipe Pabon (787)274-0904 Recruiting 010419. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Jill Utech (901)495-3490 Recruiting 010509. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 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 (650)723-2804 Recruiting 010314. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010522. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 010712. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 010528. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 010405. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010502. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010405. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010508. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010405. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010405. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010405. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 010502. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010528. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Rachele Cruz (716)898-3933 Recruiting 010517. NEW YORK Cornell Clinical Trials Unit 119 West 24th St / Ground Floor New York, NY 10011 Todd Stroberg (212)746-4178 Recruiting 010528. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 010502. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Valery Hughes (212)746-4393 Recruiting 010528. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 010314. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 010612. TEXAS Children's Med Ctr of Dallas 1935 Motor St Dallas, TX 75235 Dewan Perry (214)456-6198 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 (868)623-5834 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 (415)514-0550 Recruiting 010625. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010625. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010625. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 010702. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 010731. HAWAII Queens Med Ctr Leahi Hospital / Young Building / 3675 Kilauea Ave Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010625. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010625. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010625. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010625. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010625. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010625. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010625. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 010625. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 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 (916)973-6472 Recruiting 010619. CALIFORNIA AIDS Research Alliance 621-A North San Vicente Blvd West Hollywood, CA 90069 Stephen Brown (310)358-2429 Recruiting 010619. CALIFORNIA Park Ctr for Health / Keith Vrhel 4067 Park Blvd San Diego, CA 92103 Keith Vrhel (619)296-0224 Recruiting 001219. CALIFORNIA Orange County Ctr for Special Immunology 11190 Warner Ave Fountain Valley, CA 92708 Paul Cimoch (714)751-5800 Recruiting 001219. CALIFORNIA AIDS Healthcare Foundation 1300 North Vermont Ave / Suite 606 Los Angeles, CA 90027 Charles Farthing (323)913-3953 Recruiting 001219. CALIFORNIA LAGLC 1625 N Schrader Blvd Rm 319 Los Angeles, CA 90028 Robert Bolan (323)993-7577 Recruiting 010619. DISTRICT OF COLUMBIA Dupont Circle Physicians Group 1737 20th St NW Washington, DC 200091104 Richard Elion (202)745-0201 Recruiting 010619. FLORIDA Infectious Diseases Associates 1425 South Osprey Ave Sarasota, FL 34239 Vilma Vega (941)366-0776 Recruiting 001219. FLORIDA CRI of South Florida 1320 South Dixie Hwy Coral Gables, FL 33146 Allan Stein (305)667-9296 Recruiting 001219. FLORIDA Univ of Miami Dept of Medicine 1800 Northwest 10th Ave / R-60A Miami, FL 33136 Margaret A Fischl (305)243-3847 Recruiting 010619. FLORIDA Infectious Disease Research Inst 4620 N Habana Ave Tampa, FL 33614 Bienvenido Yangco (813)875-4374 Recruiting 001219. FLORIDA Specialty Med Care Ctrs of South Florida Inc 1313 NW 36th St Miami, FL 33142 Ronald Lubetsky (305)634-7700 Recruiting 001219. FLORIDA Gary Richmond MD 315 Southeast 14th St Fort Lauderdale, FL 33316 Gary Richmond (954)524-2250 Recruiting 001219. FLORIDA Jeffrey Levenson 6798 Crosswinds St Petersburg, FL 33710 Jeffrey Levenson (727)344-4250 Recruiting 001219. FLORIDA Infectious Disease Consultants 685 Palm Springs Dr Altamonte Springs, FL 32701 Edwin DeJesus (407)647-3960 Recruiting 001219. FLORIDA Therafirst Med Ctr 4011 North Federal Hwy Fort Lauderdale, FL 33308 Anthony LaMarca (954)564-4222 Recruiting 001219. GEORGIA SMO USA 1820 Highway 20 Conyers, GA 30013 Gerald Pierone (561)770-2664 Recruiting 001219. GEORGIA Med College of Georgia 1521 Pope Ave / Bldg FF119 Augusta, GA 30912 Cheryl Newman (706)721-9683 Recruiting 010619. GEORGIA AIDS Research Consortium of Atlanta 131 Ponce de Leon Ave Atlanta, GA 30308 Melanie A Thompson (404)876-2317 Recruiting 001219. INDIANA Indiana Univ Med School 1001 West 10th St Indianapolis, IN 46202 Lawrence Wheat (317)630-6262 Recruiting 010619. MASSACHUSETTS Hawthorne Med Associates / PAACA 4586A Acushnet Ave New Bedford, MA 02745 Andrew Artenstein (508)961-2970 Recruiting 001219. MASSACHUSETTS Brigham and Women's Hosp 75 Francis St Boston, MA 02115 Paul Sax (617)732-8881 Recruiting 010619. MINNESOTA Abbott-Northwestern Hosp / Clinic 42 2545 Chicago Ave South Minneapolis, MN 55404 Frank Rhame (612)863-5336 Recruiting 010619. MISSOURI Southampton Healthcare Inc 2340 Hampton Ave St Louis, MO 63139 David Parks (314)647-2200 Recruiting 001219. NEW JERSEY VAMC New Jersey Healthcare System 385 Tremont Ave East Orange, NJ 07018 Robert Eng (973)676-1000 Recruiting 010619. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Ronald Poblete (973)483-3444 Recruiting 010619. NEW YORK Bronx Veterans Affairs Med Ctr 130 West Kingsbridge Rd Bronx, NY 10468 Sheldon Brown (718)584-9000 Recruiting 010619. NEW YORK North Shore Univ Hosp 300 Community Dr Manhasset, NY 11030 David Shepp (516)562-4280 Recruiting 010619. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Ross Hewitt (716)898-4119 Recruiting 010619. NEW YORK St Lukes - Roosevelt Hosp Ctr 432 West 58th St New York, NY 10019 George McKinley (212)523-6743 Recruiting 010619. OHIO Univ of Cincinnati / Holmes Hosp Eden and Albert Sabin Way Cincinnati, OH 452670405 Judith Feinberg (513)584-5897 Recruiting 010619. PENNSYLVANIA Hahnemann Univ Hosp Broad and Vine Sts / MS 209 Philadelphia, PA 19102 Daniel Alvarez (215)762-3227 Recruiting 010619. PENNSYLVANIA Milton S Hershey Med Ctr 500 Univ Dr Hershey, PA 170330850 Elaine Eyster (717)531-8399 Recruiting 010619. SOUTH CAROLINA Burnside Clinic 14 Calendar Ct Columbia, SC 29206 Alfred Burnside (803)787-1113 Recruiting 001219. TENNESSEE Methodist Healthcare 1265 Union Avenue Memphis, TN 38104 Danny Lancaster (901)726-8255 Recruiting 010619. TEXAS Joseph C Gathe 1200 Binz / Suite 120 Houston, TX 77004 Joseph Gathe (713)526-9821 Recruiting 001219. TEXAS Nicholas Bellos 3801 Gaston Ave Suite 300 Dallas, TX 75246 Lee Ann OIiver (214)828-4702 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 (205)975-7925 Recruiting 010423. CALIFORNIA Univ of California San Francisco 3180 18th St San Francisco, CA 94110 Julieann Lewis (415)514-0550 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 (303)372-5535 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 (212)263-6565 Recruiting 010502. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Dilcia Ortega (212)241-6886 Recruiting 010423. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 010318. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010418. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 010406. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 010423. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010522. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Chip Lohner (214)590-0414 Recruiting 010627. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (310)358-2300 Recruiting 010105. CALIFORNIA Pacific Horizons Med Group 2351 Clay St San Francisco, CA 94115 Amy Sullivan (415)292-5477 Recruiting 010104. CALIFORNIA Altamed Medical Health Services 5427 East Whittier Blvd Los Angeles, CA 90022 Monica Lopez (323)869-5429 Recruiting 010104. DISTRICT OF COLUMBIA George Washington Univ Med Ctr 2150 Pennsylvania Ave NW Washington, DC 20037 Scott Watson (202)994-2417 Recruiting 010105. FLORIDA Community Research Initiative of South Florida 1320 South Dixie Hwy Coral Gables, FL 33146 Jean Telusma (305)661-1150 Recruiting 010105. GEORGIA Atlanta VA Med Ctr 1670 Clairmont Rd Mailstop RIM-111 Decatur, GA 30033 Laura Gallager (404)321-6111 Recruiting 010105. MICHIGAN Wayne State Univ - WSU/DMC / Univ Hlth Ctr 4201 Saint Antoine / POD 7C Detroit, MI 48201 Jan Kosmyna (313)993-0923 Recruiting 010104. MINNESOTA Park Nicollet Med Ctr / Hlth Education 3800 Park Nicollet Blvd / 6th Floor St Louis Park, MN 55416 Renee St Jacque (612)993-2066 Recruiting 010104. NORTH CAROLINA Jemsek Clinic 16630 Northcross Dr / Suite 102 Huntersville, NC 28078 Paula Hutcherson (704)987-2111 Recruiting 010104. NEW YORK Treatment for Life Ctr One Brookdale Plaza Brooklyn, NY 112123198 Victor Bouzi (917)433-8597 Recruiting 010104. PENNSYLVANIA Bornemann Internal Medicine 145 N 6th Street / Suite 205 Reading , PA 19601 Paula Shivers (610)378-2561 Recruiting 010105. SOUTH CAROLINA Burnside Clinic 14 Calendar Ct Columbia, SC 29206 Dan Woodward (803)787-1113 Recruiting 010104. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 010105. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd / KI - 900 Dallas, TX 75235 Claudia Quittner (214)648-9296 Recruiting 010105. VIRGINIA Hampton Roads Med Specialists 2112 Executive Dr Hampton, VA 23666 Lois H Ullman (757)838-8677 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 (949)646-1111 Recruiting 001215. CALIFORNIA AIDS Healthcare Foundation 1300 North Vermont Ave / Suite 606 Los Angeles, CA 90027 Charles Farthing (323)913-3953 Recruiting 010713. FLORIDA Saint Josephs Comprehensive Research Institute 4200 N Armenia Ave / Suite 3 Tampa, FL 33607 Allis Emnett (813)870-4760 Recruiting 001215. FLORIDA Bach and Godofsky 101 Riverfront Blvd / Suite 460 Bradenton, FL 34205 Debra Blanco (941)746-2711 Recruiting 010713. ILLINOIS Northstar Med Clinic 2835 North Sheffield Ave Chicago, IL 60657 Harriett Wittert (773)296-2400 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 (415)514-0550 Recruiting 010205. CALIFORNIA San Francisco VA Med Ctr 3180 18th St San Francisco, CA 941104206 Julieann Lewis (415)514-0550 Recruiting 010205. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010124. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010522. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 010316. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Ericka Patrick (404)616-6313 Recruiting 010517. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010316. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010502. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Charles Raines (410)614-4487 Recruiting 010723. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 010423. MISSOURI Washington Univ / St Louis Connect Care 4511 Forest Park Parkway / Suite 304 Saint Louis, MO 63108 Mike Klebert (314)454-0058 Recruiting 010522. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 010517. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 Recruiting 010627. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010522. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010213. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010410. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010316. RHODE ISLAND Brown Univ / Miriam Hosp 164 Summit Ave / Immunology Ctr Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010316. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (713)526-9821 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 (650)723-2804 Recruiting 010119. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010118. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010222. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 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 (212)263-6565 Recruiting 010323. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010118. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 001215. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010222. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 No longer recruiting 010417. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Chip Lohner (214)590-0414 Recruiting 010316. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (310)206-6369 Recruiting 010119. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 010406. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 010222. CALIFORNIA Los Angeles County - USC Med Ctr 1640 Marengo St Los Angeles, CA 90033 Eva Operskalski (323)226-2342 Recruiting 010119. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Mary Caffery (619)543-8080 Recruiting 010503. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 010627. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 010418. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Julie Ziegler (202)884-4708 Recruiting 010316. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 010222. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 010228. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 010502. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Lucrecia Rios (312)572-4547 Recruiting 010517. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Margaret Cowie (504)586-3804 Recruiting 001129. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Kirk Bertelsen (617)355-8189 Recruiting 010410. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 001110. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 010517. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 010318. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 010410. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Lisa Cerrachio (732)235-7894 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 (973)972-3118 Recruiting 001110. NEW YORK Montefiore Medical / AECOM 1300 Morris Park Ave Bronx, NY 19461 Gayle Kreinik (718)430-2940 Recruiting 010723. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 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 (516)444-1313 Recruiting 010418. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 010207. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 001110. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 010423. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 010406. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 010502. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 010117. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 001110. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 010207. PENNSYLVANIA Saint Christopher's Hosp for Children Erie Ave at Front St Philadelphia, PA 191341095 Roslynn Buie (215)427-8443 Recruiting 010418. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Anne Cope (803)792-2385 Recruiting 010418. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 001110. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 010406. VIRGINIA Children's Hosp of the King's Daughters 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 Recruiting 001110. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (323)343-8283 Recruiting 001229. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 001229. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 001229. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Mario Guerrerro (310)222-3848 Recruiting 010111. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010111. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 001229. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010406. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (303)372-5535 Recruiting 010618. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010618. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 Recruiting 010618. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 No longer recruiting 010612. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 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 (205)975-7925 Recruiting 010108. CALIFORNIA San Francisco VA Med Ctr 3180 18th St San Francisco, CA 941104206 Julieann Lewis (415)514-0550 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 (323)343-8283 Recruiting 010118. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 010119. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 010318. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010119. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010522. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010612. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010119. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010119. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010119. MASSACHUSETTS Brigham and Women's Hosp Div of Infectious Diseases / 15 Francis St PBB A-4 Boston, MA 02215 Carolyn Koziol (617)732-5635 Recruiting 010731. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 010109. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010118. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 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 (212)263-6565 Recruiting 010323. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 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 (516)444-1313 Recruiting 010731. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 010119. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010108. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Felipe Pabon (787)274-0904 Recruiting 010424. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 010119. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010118. RHODE ISLAND Brown Univ / The Miriam Hosp 164 Summit Ave / Research Building / Room 215 Providence, RI 02906 Joan Gormley (401)331-8500 Not yet recruiting 010118. RHODE ISLAND Brown Univ / Miriam Hosp 164 Summit Ave / Immunology Ctr Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010118. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 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 (212)448-5020 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 (205)975-7925 Recruiting 010528. CALIFORNIA Univ of California San Francisco 3180 18th St San Francisco, CA 94110 Julieann Lewis (415)514-0550 Recruiting 010117. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 010228. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 010323. CALIFORNIA San Francisco VA Med Ctr 3180 18th St San Francisco, CA 941104206 Julieann Lewis (415)514-0550 Recruiting 010117. CALIFORNIA Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium 751 South Bascom Ave San Jose, CA 951282699 Debbie Slamowitz (650)723-2804 Recruiting 010119. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 001129. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Mario Guerrerro (310)222-3848 Recruiting 010522. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 Recruiting 001129. COLORADO Denver Dept of Health and Hosps 4200 East 9th Ave / Campus Box B-196 Denver, CO 80262 M Graham Ray (303)372-5535 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 (303)372-5535 Recruiting 010117. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010205. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Ericka Patrick (404)616-6313 Recruiting 010406. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010119. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 Recruiting 010119. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010228. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010410. MASSACHUSETTS Brigham and Women's Hosp Div of Infectious Diseases / 15 Francis St PBB A-4 Boston, MA 02215 Carolyn Koziol (617)732-5635 Recruiting 010222. MASSACHUSETTS Harvard (Massachusetts Gen Hosp) 55 Fruit St / Founders Bldg 8th Floor Boston, MA 02114 Teri Flynn (617)726-3819 Recruiting 010222. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 010213. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Charles Raines (410)614-4487 Recruiting 010723. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010522. NORTH CAROLINA Moses H Cone Memorial Hosp 1200 North Elm St Greensboro, NC 27401 Lisa Dasnoit (336)832-8062 Recruiting 010405. NORTH CAROLINA Carolinas Med Ctr PO Box 32861 Charlotte, NC 28232 Sharon Hewat (704)355-7266 Recruiting 010228. NORTH CAROLINA Carolinas Med Ctr 1000 Blythe Blvd / MEB 202 Charlotte, NC 28203 Marjorie Massey (704)355-7266 Recruiting 010119. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 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 (212)263-6565 Recruiting 010406. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 010119. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Rachele Cruz (716)898-3933 Recruiting 010323. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 Recruiting 010119. NEW YORK Cornell Clinical Trials Unit 119 West 24th St / Ground Floor New York, NY 10011 Todd Stroberg (212)746-4178 Recruiting 010222. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 010213. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Valery Hughes (212)746-4393 Recruiting 010213. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010405. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010318. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 010316. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 010205. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 010405. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010730. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 010115. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010405. RHODE ISLAND Brown Univ / Miriam Hosp 164 Summit Ave / Immunology Ctr Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010405. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 010222. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 010612. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 010119. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (212)448-5020 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 (205)975-7925 Recruiting 010727. CALIFORNIA Univ of California San Francisco 3180 18th St San Francisco, CA 94110 Julieann Lewis (415)514-0550 Recruiting 010727. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 010727. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 010727. CALIFORNIA San Francisco VA Med Ctr 3180 18th St San Francisco, CA 941104206 Julieann Lewis (415)514-0550 Recruiting 010727. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 010727. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 010727. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Mario Guerrerro (310)222-3848 Recruiting 010727. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 Recruiting 010727. COLORADO Denver Dept of Health and Hosps 4200 East 9th Ave / Campus Box B-196 Denver, CO 80262 M Graham Ray (303)372-5535 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 (303)372-5535 Recruiting 010727. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 010727. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Beth Dean (404)616-0654 Recruiting 010727. HAWAII Tripler Army Med Ctr Infectious Disease Services MCHK-DMI / One Jarrett White Rd Tripler AMC, HI 96859 Ross Newmann (808)433-6504 Recruiting 010727. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010727. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 010727. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010727. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010727. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010727. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010727. MASSACHUSETTS Brigham and Women's Hosp Div of Infectious Diseases / 15 Francis St PBB A-4 Boston, MA 02215 Carolyn Koziol (617)732-5635 Recruiting 010727. MASSACHUSETTS Harvard (Massachusetts Gen Hosp) 55 Fruit St / Founders Bldg 8th Floor Boston, MA 02114 Teri Flynn (617)726-3819 Recruiting 010727. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 010727. MASSACHUSETTS Boston Med Ctr 1 Boston Med Ctr Place / Dowling Bldg Boston, MA 02118 Beth Hankin (617)414-7831 Recruiting 010727. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Charles Raines (410)614-4487 Recruiting 010727. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 010727. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010727. NORTH CAROLINA Moses H Cone Memorial Hosp 1200 North Elm St Greensboro, NC 27401 Lisa Dasnoit (336)832-8062 Recruiting 010727. NORTH CAROLINA Carolinas Med Ctr 1000 Blythe Blvd / MEB 202 Charlotte, NC 28203 Marjorie Massey (704)355-7266 Recruiting 010727. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 Recruiting 010727. NEBRASKA Univ of Nebraska Med Ctr 985130 Nebraska Med Ctr Omaha, NE 681985130 Frances Van Meter (402)559-8163 Recruiting 010727. NEW YORK St Mary's Hosp (Univ of Rochester/Infectious Diseases) 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 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 (212)263-6565 Recruiting 010727. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010727. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 010727. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Ross Hewitt (716)898-4119 Recruiting 010727. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 Recruiting 010727. NEW YORK Cornell Clinical Trials Unit 119 West 24th St / Ground Floor New York, NY 10011 Todd Stroberg (212)746-4178 Recruiting 010727. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 010727. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010727. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Valery Hughes (212)746-4393 Recruiting 010727. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 010727. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010727. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 010727. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 010727. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 010727. PENNSYLVANIA Univ of Pennsylvania 536 Johnson Pavillion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010727. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 010727. PENNSYLVANIA Philadelphia Veterans Administration Med Ctr 536 Johnson Pavilion Philadelphia, PA 19104 Joseph Quinn (215)349-8092 Recruiting 010727. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010727. RHODE ISLAND Brown Univ / Miriam Hosp 164 Summit Ave / Immunology Ctr Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 010727. RHODE ISLAND Rhode Island Hosp / Brown Univ 593 Eddy St Providence, RI 02903 Carolyn Dwyer (401)467-9884 Recruiting 010727. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 010727. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 010727. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 Recruiting 010727. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 010727. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (415)514-0550 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 (323)343-8283 Recruiting 000906. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Beth Dean (404)616-0654 Recruiting 001109. ILLINOIS Cook County Hosp 1835 W Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 001109. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 001109. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 001109. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 001109. NEBRASKA Univ of Nebraska Med Ctr 985130 Nebraska Med Ctr Omaha, NE 681985130 Frances Van Meter (402)559-8163 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 (212)263-6565 Recruiting 001109. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 001109. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 001109. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 000906. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 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 (212)448-5126 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 (619)543-8080 Recruiting 000816. MARYLAND Johns Hopkins Hosp 600 N Wolfe St / Osler 525 Baltimore, MD 21287 Michelle Parish (410)614-1338 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 (205)975-9657 Recruiting 001122. CALIFORNIA St Lukes Medical Group 1855 First Ave San Diego, CA 92101 Rebecca Gonzalez (619)235-0501 Recruiting 000823. CALIFORNIA Robert Smith Medical Group 2850 6th Ave 5th Floor / Suite 502 San Diego, CA 92103 Carolyn Sircle (619)296-5590 Recruiting 001122. CALIFORNIA Saint Francis Mem Hosp / HIV Care 900 Hyde St San Francisco, CA 94109 Mark Bowers (415)353-6215 Recruiting 010405. CALIFORNIA Mem Med Group Inc 2699 Atlantic Ave Long Beach, CA 90806 Debbie Mendoza (562)426-3333 Recruiting 010614. CALIFORNIA East Bay Clinical Trial Ctr 2700 Grant St / Suite 200 Concord, CA 94520 Judy Harbison (925)687-8860 Recruiting 001122. CALIFORNIA Davies Med Ctr 45 Castro St / Suite 415 San Francisco, CA 94114 John Kopchak (415)565-6288 Recruiting 001127. CALIFORNIA Orange Coast Med Group 361 Hosp Rd Suite 126 Newport Beach, CA 92663 Charles Walworth (949)646-1111 Recruiting 000823. CALIFORNIA East Bay AIDS Ctr 2850 Telegraph Ave Berkeley, CA 94705 Lucinda Hopewell (510)204-1291 Recruiting 001122. CALIFORNIA AIDS Healthcare Foundation 1300 North Vermont Ave Los Angeles, CA 90027 Rubin Vidales (323)913-3953 Recruiting 001122. COLORADO Univ of Colorado Health Ctr / Denver Gen Hosp 4200 East 9th Ave Denver, CO 80262 Kristin Doherty (303)315-0089 Recruiting 751101. COLORADO Beacon Clinic / Boulder Community Hosp 1155 Alpine St Boulder, CO 80304 Anil Modak (303)938-3174 Recruiting 001127. CONNECTICUT Blick Med Associates 589 Bedford St Stamford, CT 06901 Trish Garton (203)357-7800 Recruiting 001122. DISTRICT OF COLUMBIA George Washington Univ Med Ctr 2150 Pennsylvania Ave NW Washington, DC 20037 Suzanne Schuck (202)994-0006 Recruiting 001127. DISTRICT OF COLUMBIA Physicans Home Service 2311 M Street NW / Suite 401 Washington, DC 20037 Alex Seymour (202)331-3888 Recruiting 001122. FLORIDA Hillsborough County Health Department 1105 E Kennedy Ave / Specialty Care Center Tampa, FL 33602 Kathleen Mason (813)307-8003 Recruiting 010614. FLORIDA Infectious Diseases Associates 1425 South Osprey Ave Sarasota, FL 34239 Pat Carr (941)366-0776 Recruiting 000823. FLORIDA Health Positive 3135 State Road 580 Safety Harbor, FL 34695 Beverly Wilson (727)725-9931 Recruiting 001122. FLORIDA Infectious Disease Research Inst 4620 N Habana Ave Tampa, FL 33614 Kalliope Halkias (813)875-4374 Recruiting 001122. FLORIDA Gary Richmond MD 315 Southeast 14th St Fort Lauderdale, FL 33316 Vernon Appleby (954)524-2250 Recruiting 000823. FLORIDA South Miami Hosp 7000 Southwest 62nd Ave / Suite 650 Miami, FL 33143 Leon Aquino (305)668-9488 Recruiting 010614. FLORIDA Wohlfeiler Piperator & King MD PA 1680 Meridian Ave / Suite 200 Miami Beach, FL 33139 Irene Trujillo (305)538-1400 Recruiting 001122. FLORIDA Larry Bush National Research Associates / 3175 S Congress Ave / #103 Palm Springs, FL 33461 Jennifer Burke (561)357-9441 Recruiting 000824. GEORGIA Infectious Disease Specialists of Atlanta 2665 N Decatur Rd / Suite 330 Decatur, GA 30033 Katie McClure (404)297-9755 Recruiting 000823. GEORGIA Ingenix Kern McNeill Decatur 35 Collier Rd Atlanta, GA 30309 Theresa McGhee (404)351-8873 Recruiting 001127. GEORGIA Harbin Clinic 1825 Martha Berry Blvd Rome, GA 30165 Sharon Vaughan (706)238-8036 Recruiting 010614. ILLINOIS Northstar Med Clinic 2835 North Sheffield Ave Chicago, IL 60657 Harriett Wittert (773)296-2400 Recruiting 000823. LOUISIANA Tulane Univ Med Ctr / Infectious Diseases Sect 1430 Tulane Ave New Orleans, LA 70112 Kathleen Brumfield (504)584-3606 Recruiting 010614. MASSACHUSETTS New England Med Ctr 750 Washington St Boston, MA 02111 Betsy Adams (617)636-8186 Recruiting 010614. MASSACHUSETTS Fenway Community Health Ctr 7 Haviland St Boston, MA 02115 Linda Pitler (617)927-6056 Recruiting 010614. MARYLAND Institute of Human Virology 725 W Lombard St Baltimore, MD 21201 Sandy Zaremba (410)706-1476 Recruiting 010614. MINNESOTA Abbott-Northwestern Hosp / Clinic 42 2545 Chicago Ave South Minneapolis, MN 55404 Joann Armstrong (612)863-5336 Recruiting 001122. NEW JERSEY South Jersey Infectious Diseases Inc 732 Shore Rd Somers Point, NJ 08244 Sherry Jurasinski (609)927-6662 Recruiting 000823. NEW YORK Mount Sinai School of Medicine One Gustave Levy Place New York, NY 10029 Dilcia Ortega (212)241-6886 Recruiting 001122. NEW YORK Liberty Medical / Cabrini Hospital / Dept of Infec Diseases 232 East 20th St / 2nd floor New York, NY 10003 Rose Turelli (212)995-6907 Recruiting 000823. NEW YORK Dr Lawrence Fontana 117 East 18th St / First Floor New York, NY 10003 Gary Wenc (212)420-1303 Recruiting 001127. NEW YORK Howard Grossman 155 West 19 St / 4th Floor New York, NY 10011 Gervais Frechette (212)929-2629 Recruiting 001127. NEW YORK North Shore Univ Hosp / Div of Infectious Diseases 300 Community Dr Manhasset, NY 11030 Pam O'Byrne (516)562-1528 Recruiting 001122. NEW YORK Erie County Med Ctr 462 Grider St Buffalo, NY 14215 Brenda Stamos (716)898-4119 Recruiting 001122. NEW YORK Albert Einstein College of Medicine 1300 Morris Park Ave Bronx, NY 10461 Gayle Kreinik (718)430-2940 Recruiting 010614. OREGON Fanno Creek Clinic 2400 SW Vermont St Portland, OR 97219 Michael Schillen (503)452-0915 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 (114)981-7777 Recruiting 000823. OTHER Hospital de Agudos JM Ramos Mejia Urquiza 609 Sector G / Departmento de Inmunocomprometidos / 122Capital Federal Buenos Aires, Marcelo Losso (114)931-5252 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 (905)521-2100 Recruiting 001122. OTHER San Juan Veterans Administration Med Ctr 10 Casia St San Juan, PR 009275800 Zyndia Pomales (787)641-7582 Recruiting 010614. OTHER Montreal Gen Hosp 1650 Cedar Ave Montreal, QC James Vatistas (514)934-8035 Recruiting 010614. OTHER Centre De Recherche En Infectiologie 2705 Boul Laurier Ste-Foy , QC Lyne LaPointe (418)656-4141 Recruiting 010614. RHODE ISLAND Paragon Clinical Research 1150 Resovoir Ave / Suite 103 Cranston, RI 02920 Irene Dupont (401)943-8685 Recruiting 001122. SOUTH CAROLINA Coastal Carolina Research Ctr 266 West Coleman Blvd Mount Pleasant, SC 29464 Kathleen C Fletcher (843)856-3784 Recruiting 001122. TEXAS Walter Gaman 1110 Cottonwood Lane / Suite 200 Irving, TX 75038 Andy Longoria (972)258-7482 Recruiting 000829. TEXAS Houston Clinical Research Network 215 Westheimer Houston, TX 77006 Jesse Rios (713)830-3050 Recruiting 001122. TEXAS Central Texas Clinical Research 1015 East 32nd Street / Suite 215 Austin, TX 78705 Peggy Wright (512)480-9660 Recruiting 001122. TEXAS Nelson Tebedo Health Resource Ctr 4012 Cedar Springs Dallas, TX 75219 Jimmy Garza (214)528-2336 Recruiting 001127. TEXAS Univ TX Galveston Med Branch 301 University Blvd Galveston, TX 77555 Cheryl Coufal (409)772-3991 Recruiting 001122. TEXAS Diversified Med Practices PA 4126 Southwest Freeway Houston, TX 77027 Barbara Knight (713)961-7191 Recruiting 001127. TEXAS Amelia Ct Clinic 1936 Amelia Ct Dallas, TX 75235 Tianna Peterson (214)590-2686 Recruiting 001122. WASHINGTON Swedish Med Ctr / Dr Peter Shalit 1120 Cherry St Seattle, WA 98104 Janice Price (206)386-2523 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 (205)975-7925 Recruiting 000907. CALIFORNIA Univ of California San Francisco 3180 18th St San Francisco, CA 94110 Julieann Lewis (415)514-0550 Recruiting 010406. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 000907. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 000907. CALIFORNIA Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium 751 South Bascom Ave San Jose, CA 951282699 Debbie Slamowitz (650)723-2804 Recruiting 000907. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 001013. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Mario Guerrerro (310)222-3848 Recruiting 000907. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 001006. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 000912. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Beth Dean (404)616-0654 Recruiting 010119. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 000907. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 001219. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 000907. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 000907. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 000907. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 010118. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 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 (212)263-6565 Recruiting 001018. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 000922. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 No longer recruiting 010320. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 010207. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 001025. PENNSYLVANIA Philadelphia Veterans Administration Med Ctr 536 Johnson Pavilion Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 001018. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 001025. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 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 (415)476-9296 Recruiting 001017. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 No longer recruiting 010501. CALIFORNIA Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium 751 South Bascom Ave San Jose, CA 951282699 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 001017. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 Recruiting 001017. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 No longer recruiting 010501. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 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 (303)372-5535 Recruiting 001017. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 001017. HAWAII Queens Med Ctr Leahi Hospital / Young Building / 3675 Kilauea Ave Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 001024. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 001017. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 Recruiting 001024. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 001017. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 010118. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 010118. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 010118. MASSACHUSETTS Brigham and Women's Hosp Div of Infectious Diseases / 15 Francis St PBB A-4 Boston, MA 02215 Carolyn Koziol (617)732-5635 Recruiting 001017. MASSACHUSETTS Harvard (Massachusetts Gen Hosp) 55 Fruit St / Founders Bldg 8th Floor Boston, MA 02114 Teri Flynn (617)726-3819 Recruiting 001017. MASSACHUSETTS Boston Med Ctr 1 Boston Med Ctr Place / Dowling Bldg Boston, MA 02118 Beth Hankin (617)414-7831 Recruiting 001025. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Denise Wright (410)614-4266 Recruiting 010723. MARYLAND State of MD Div of Corrections / Johns Hopkins Univ Hosp 1830 East Monument St / Room 8074 Baltimore, MD 212052196 Denise Wright (410)614-4266 Recruiting 001017. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 010205. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 001017. NORTH CAROLINA Carolinas Med Ctr PO Box 32861 Charlotte, NC 28232 Sharon Hewat (704)355-7266 Recruiting 010118. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Cheryl Marcus (919)843-8761 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 (212)263-6565 No longer recruiting 010213. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 No longer recruiting 010320. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 Recruiting 001019. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 001017. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 No longer recruiting 010320. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 001017. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 001017. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 001017. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 No longer recruiting 010627. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 001025. PENNSYLVANIA Philadelphia Veterans Administration Med Ctr 536 Johnson Pavilion Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 001031. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 001116. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 001017. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 Recruiting 001017. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 001017. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (205)558-2328 Recruiting 010318. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 001024. CALIFORNIA Los Angeles County - USC Med Ctr 1640 Marengo St Los Angeles, CA 90033 Eva Operskalski (323)226-2342 Recruiting 000922. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Mary Caffery (619)543-8080 Recruiting 010530. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 001019. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 Recruiting 010109. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Julie Ziegler (202)884-4708 Recruiting 000726. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 000915. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 001006. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 001110. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 000824. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 000726. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 Recruiting 001205. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 Recruiting 000817. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 000914. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 001116. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Lucrecia Rios (312)572-4547 Recruiting 010517. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Bishop (617)355-8198 Recruiting 000914. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 000829. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 000629. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 000801. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MARYLAND Univ of Maryland at Baltimore / Univ Med Ctr 700 W Lombard Street / 2nd Floor Baltimore, MD 21201 Kara Fore (410)706-8933 Recruiting 010612. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 010406. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Lisa Cerrachio (732)235-7894 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 (973)972-3118 Recruiting 000614. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 001024. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 010405. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 001205. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 010318. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 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 (516)444-1313 Recruiting 000915. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 010316. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 001116. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 000922. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 000829. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 000726. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Maria del Pilar Thurin (787)765-4186 Recruiting 001012. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 000922. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Anne Cope (803)792-2385 Recruiting 010119. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 001116. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 010115. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 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 (415)476-9554 Recruiting 000614. COLORADO Denver CPCRA / Denver Public Hlth 605 Bannock St Denver, CO 802044507 Jack Rouff (303)436-7184 Recruiting 000614. CONNECTICUT Yale U / New Haven Med Ctr / AIDS Clinical Trials Unit 135 College St / Suite 323 New Haven, CT 065102483 Laurie Andrews (203)785-3557 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 (202)745-8301 Recruiting 000614. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd #108 Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting 000614. LOUISIANA Louisiana Comm AIDS Rsch Prog / Tulane Univ Med 1430 Tulane Ave / TB 21 New Orleans, LA 70112 Janice Walker (504)584-1971 Recruiting 000614. MICHIGAN Henry Ford Hosp 2799 West Grand Blvd / CFP-104 Detroit, MI 48202 Diane Mastro-Polak (313)876-2798 Recruiting 000614. MICHIGAN Wayne State Univ - WSU/DMC / Univ Hlth Ctr 4201 Saint Antoine / POD 7C Detroit, MI 48201 Jan Kosmyna (313)993-0923 Recruiting 000614. NEW JERSEY Southern New Jersey AIDS Clinical Trials Dept of Medicine / 3 Cooper Plaza / Suite 513 Camden, NJ 08103 Carol Graeber (856)963-6890 Recruiting 000614. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Robert C Sawyer (973)483-3444 Recruiting 000614. NEW YORK Bronx-Lebanon Hosp Ctr Vaccine Trial Site / 1645 Grand Concourse Suite 1G Bronx, NY 10453 Elizabeth Doramajian (718)901-6346 Recruiting 010118. NEW YORK Harlem AIDS Treatment Grp / Harlem Hosp Ctr 506 Lenox Ave / Rm 3101A New York, NY 10037 Luis Fuentes (212)939-2957 Recruiting 000614. OREGON The Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 No longer recruiting 000111. PENNSYLVANIA Philadelphia FIGHT 1233 Locust St / 5th Floor Philadelphia, PA 19107 Barbara Gallagher (215)985-4448 Recruiting 000614. TEXAS Montrose Clinic 215 Westheimer Rd Houston, TX 77006 Brian Bell (713)830-3011 Recruiting 010119. TEXAS Houston Veterans Administration Med Ctr 2002 Holcombe Blvd Houston, TX 77030 Katharine Breaux (713)794-7943 Recruiting 010115. TEXAS Univ TX Health Science Ctr 6431 Fannin St Houston, TX 77030 Hilda Cuervo (713)500-6751 Recruiting 010115. VIRGINIA Richmond AIDS Consortium / Div of Infect Diseases PO Box 980049 Richmond, VA 232980049 Vinnie Mitchell (757)828-2477 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 (205)975-2839 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 (410)955-7283 No longer recruiting 010409. MARYLAND Univ of Maryland Institute of Human Virology 725 W Lombard St Baltimore, MD 212011192 Lynda Nerhood (866)448-4448 Recruiting 010606. MISSOURI Saint Louis Univ Health Sciences Ctr Division of Infectious Diseases / 3635 Vista Ave / FDT-8N Saint Louis, MO 63110 Carolyn Novotny (314)577-8648 No longer recruiting 010409. NEW YORK Univ of Rochester Med Ctr Box 689 / 601 Elmwood Ave Rochester, NY 14642 Shirley Erb (716)275-5871 No longer recruiting 010409. NEW YORK Columbia Univ 630 West 168th St New York, NY 10032 Jolene Noel-Connor (212)305-6795 Recruiting 010529. NEW YORK New York Blood Ctr Project ACHIEVE / 1309 Fulton Ave Room 312 Bronx, NY 10456 Pamela Brown-Peterside (718)588-8900 Recruiting 010529. RHODE ISLAND Miriam Hosp 164 Summit Ave Providence, RI 02906 Gail Yates (401)793-4335 Recruiting 010503. TENNESSEE Vanderbilt Univ Hosp A-3310 MCN / 21st and Garland Nashville, TN 37232 Lois Wagner (615)343-6260 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 (206)667-2300 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 (205)975-7925 Recruiting 000817. CALIFORNIA Marin County Specialty Clinic 161 Mitchell Building Suite 200 San Rafael, CA 94903 Marc Gould (415)476-9296 Recruiting 000817. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 000922. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 000810. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 Recruiting 000817. CALIFORNIA Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium 751 South Bascom Ave San Jose, CA 951282699 Debbie Slamowitz (650)723-2804 Recruiting 000817. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 000817. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 000914. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 000817. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3838 Recruiting 000829. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Beth Dean (404)616-0654 Recruiting 000817. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 000817. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 No longer recruiting 010320. ILLINOIS Cook County Hosp 1835 W Harrison St Chicago, IL 60612 Joanne Despotes (312)572-4545 Recruiting 001012. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 000817. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 000817. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 000817. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 000817. MASSACHUSETTS Harvard (Massachusetts Gen Hosp) 55 Fruit St / Founders Bldg 8th Floor Boston, MA 02114 Teri Flynn (617)726-3819 Recruiting 000914. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 000817. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Rebecca Becker (410)955-4370 Recruiting 010723. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 000817. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Barbara Longmire (919)966-7883 Recruiting 000817. NEW YORK St Mary's Hosp (Univ of Rochester/Infectious Diseases) 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 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 (212)263-6565 Recruiting 000817. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 000817. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 001012. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Ross Hewitt (716)898-4119 Recruiting 000823. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 Recruiting 000815. NEW YORK Cornell Clinical Trials Unit 119 West 24th St / Ground Floor New York, NY 10011 Todd Stroberg (212)746-4178 Recruiting 000817. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 000817. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 000817. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Valery Hughes (212)746-4393 Recruiting 000817. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 000829. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 000817. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 001006. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 001013. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 001121. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 000817. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 000823. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 000823. RHODE ISLAND Brown Univ / The Miriam Hosp 164 Summit Ave / Research Building / Room 215 Providence, RI 02906 Joan Gormley (401)331-8500 Recruiting 010108. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 000823. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 000914. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 Recruiting 000817. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 000817. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (877)858-7783 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 (888)847-2237 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 (415)476-9296 Recruiting 000424. CALIFORNIA Univ of California / San Diego Treatment Ctr 2760 5th Ave / Suite 300 San Diego, CA 921036325 Jill Kunkel (619)543-8080 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 (323)343-8283 Recruiting 001012. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 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 (303)372-5535 Recruiting 000424. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 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 (312)908-4655 Recruiting 000726. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 000614. INDIANA Wishard Hosp 550 N Univ Blvd / Room 5550 Indianapolis, IN 46202 Scott Hamilton (317)630-6023 Recruiting 000614. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Rebecca Becker (410)955-4370 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 (212)263-6565 No longer recruiting 010501. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 000424. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 000621. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 000515. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 001006. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (205)458-8700 Recruiting 000208. CALIFORNIA Avalar Medical Group 5620 Wilbur Ave / Suite 320 Tarzana, CA 91356 Toni Sparrow (818)344-5056 Recruiting 000208. CALIFORNIA Robert Scott MD 368 28th St at Summit Oakland, CA 94609 Henry Quinones (510)986-1900 Recruiting 000208. CALIFORNIA Univ of California - Davis Med Ctr / CARES 4150 V St / Suite 500 Sacramento, CA 95817 Shahrokh Jalali (916)443-3299 Recruiting 000208. CALIFORNIA AIDS Healthcare Foundation 1300 North Vermont Ave Los Angeles, CA 90027 Edwin Graham (323)913-3953 Recruiting 000208. CONNECTICUT Yale Univ School of Medicine / AIDS Program 135 College St / Suite 323 New Haven, CT 06510 Cynthia Frank (203)785-6939 Recruiting 000208. FLORIDA Community Research Initiative of South Florida 1320 South Dixie Hwy Coral Gables, FL 33146 Jean Telusma (305)661-1150 Recruiting 000208. FLORIDA Infectious Disease Research Institute 4728 North Habana Ave Tampa, FL 33614 Kalliope Halkias (813)875-4374 Recruiting 000208. FLORIDA HIV Clinical Research 300 SE 17th St Fort Lauderdale, FL 33316 Jason Villano (954)467-3006 Recruiting 000208. GEORGIA Infectious Disease Specialists of Atlanta 2665 N Decatur Rd / Suite 330 Decatur, GA 30033 Katie McClure (404)297-9755 Recruiting 000208. LOUISIANA Louisiana State Univ Med Ctr / HIV Outpatient Clinic 136 South Roman St New Orleans, LA 70112 Alison Fleury (504)568-7308 Recruiting 000208. NEW YORK St Vincents Hosp / Clinical Research Program 36 7th Ave / Suite 415 New York, NY 10011 Daisy Soto-Coppola (212)604-7625 Recruiting 000208. NEW YORK Albany Med College 47 New Scotland Ave / MC 142 Albany, NY 12208 Sandra Preston (518)262-6970 Recruiting 000208. OHIO Univ Hosps of Cleveland 2061 Cornell Rd / Foley Bldg Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 000208. OREGON The Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 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 (613)737-8879 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 (314)454-0058 Recruiting 000208. TENNESSEE Vanderbilt Univ Med Ctr 1211 Twenty-first Ave South Nashville, TN 37212 Victoria Harris (615)936-1164 Recruiting 000208. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75235 Robert Barber (214)648-2788 Recruiting 000208. TEXAS Houston Clinical Research Network / Div of Montrose Clinic 215 Westheimer Houston, TX 77006 Barbara Burkhardt (713)830-3013 Recruiting 000208. TEXAS Texas Tech Health Sciences Ctr 4800 Alberta Ave El Paso, TX 79905 Arturo Norte (915)545-6626 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 (415)476-6480 Recruiting 000713. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 000713. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 000713. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 000724. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 001012. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 000713. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 000713. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 000713. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000713. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Bishop (617)355-8198 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 (973)972-3118 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 (973)972-3118 Recruiting 000713. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 001006. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 000713. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 000713. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 001013. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 000713. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 010423. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 000713. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 000713. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 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 (205)975-7925 Recruiting 000317. CALIFORNIA Kaiser Permanente LAMC 1505 N Edgemont St / Second Floor Los Angeles, CA 90027 Mitzi St Ange (323)783-8172 Recruiting 001129. CALIFORNIA Marin County Specialty Clinic 161 Mitchell Building Suite 200 San Rafael, CA 94903 Marc Gould (415)476-9296 Recruiting 000210. CALIFORNIA Univ of California / San Diego Treatment Ctr 2760 5th Ave / Suite 300 San Diego, CA 921036325 Jill Kunkel (619)543-8080 Recruiting 000327. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 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 (323)343-8283 Recruiting 000614. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 Recruiting 000327. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 Recruiting 000210. CALIFORNIA Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium 751 South Bascom Ave San Jose, CA 951282699 Debbie Slamowitz (650)723-2804 Recruiting 000419. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 000203. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Sally Kruger (310)222-3848 Recruiting 000228. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 000327. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3841 Recruiting 000228. GEORGIA Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr 550 Peachtree St NE Atlanta, GA 303652225 Judy Powers (404)727-1339 Recruiting 000614. GEORGIA Emory Univ 341 Ponce de Leon Ave Atlanta, GA 30308 Beth Dean (404)616-0654 Recruiting 000228. HAWAII Tripler Army Med Ctr Infectious Disease Services MCHK-DMI / One Jarrett White Rd Tripler AMC, HI 96859 Ross Newmann (808)433-6504 Recruiting 000815. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 000210. IOWA Univ of Iowa Hosp and Clinic 200 Hawkins Dr Iowa City, IA 52242 Julie Katseres (319)353-8441 Recruiting 000310. ILLINOIS Cook County Hosp 637 South Wood Chicago, IL 60612 Edward Goodwin (312)572-4545 Recruiting 000317. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Jan Fritsche (312)942-5865 Recruiting 000502. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 000210. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 000310. INDIANA Division of Inf Diseases/ Indiana Univ Hosp 1001 West 10th St / OPW 430 Indianapolis, IN 46202 Beth Zwickl (317)274-8456 Recruiting 000310. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 000310. LOUISIANA Tulane Med Ctr Hosp 1415 Tulane Ave New Orleans, LA 70112 Eric Horman (504)584-3568 Recruiting 000531. MASSACHUSETTS Harvard (Massachusetts Gen Hosp) 55 Fruit St / Founders Bldg 8th Floor Boston, MA 02114 Teri Flynn (617)726-3819 Recruiting 000127. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 Recruiting 000228. MASSACHUSETTS Brigham and Women's Hosp 75 Francis St / Children's Hosp AIDS Program Boston, MA 02115 Teri Flynn (617)732-6410 Recruiting 000419. MASSACHUSETTS Boston Med Ctr 1 Boston Med Ctr Place / Dowling Bldg Boston, MA 02118 Caress Grodman (617)414-3182 Recruiting 000419. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Rebecca Becker (410)955-4370 Recruiting 010723. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 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 (314)454-0058 Recruiting 000210. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 000228. NORTH CAROLINA Moses H Cone Memorial Hosp 1200 North Elm St Greensboro, NC 27401 Pam Mentley (910)574-7888 Recruiting 000310. NORTH CAROLINA Carolinas Med Ctr 1000 Blythe Blvd / MEB 202 Charlotte, NC 28203 Marjorie Massey (704)355-7266 Recruiting 000424. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Barbara Longmire (919)966-7883 Recruiting 000228. NEBRASKA Univ of Nebraska Med Ctr 985130 Nebraska Med Ctr Omaha, NE 681985130 Frances Van Meter (402)559-8163 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 (212)263-6565 Recruiting 000127. NEW YORK Community Health Network Inc Univ of Rochester Med Center / 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 000502. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 001012. NEW YORK Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ 1230 York Ave New York, NY 10021 Arlene Hurley (212)327-7281 Recruiting 010702. NEW YORK SUNY / Erie County Med Ctr at Buffalo 462 Grider Street Buffalo, NY 14215 Ross Hewitt (716)898-4119 Recruiting 000410. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 Recruiting 000609. NEW YORK Chelsea Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St New York, NY 10021 Brenda Greenhill (212)746-4177 Recruiting 000524. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 000228. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 000228. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Brenda Greenhill (212)746-4177 Recruiting 000524. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 000310. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 000210. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Nancy Frantz (216)459-5136 Recruiting 000127. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 000327. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 000310. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 000424. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 000210. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 No longer recruiting 010222. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 000531. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (650)723-2804 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 (323)343-8283 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 (303)372-5535 Recruiting 000310. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 010323. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 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 (212)263-6565 Recruiting 000210. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 010323. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 010423. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 Recruiting 010702. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (305)243-5621 Recruiting 000111. NEW YORK SUNY at Stony Brook / Division of Infectious Diseases HSCT15 / Room 080 Stony Brook, NY 11794 Ruth Tenzler (516)444-1658 Recruiting 000111. NEW YORK Albany Med College 47 New Scotland Ave / MC 142 Albany, NY 12208 Sandra Preston (518)262-6970 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 (619)543-8080 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 (323)343-8283 Recruiting 001122. ILLINOIS Cook County Hosp 637 South Wood Chicago, IL 60612 Edward Goodwin (312)572-4545 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 (212)263-6565 Recruiting 000502. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 000310. NEW YORK Columbia Presbyterian Med Ctr Harkness Pavilion 6 Room 644 / 622 West 168th Street New York, NY 10032 Mykyelle Crawford (212)305-7897 Recruiting 000726. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 000410. TENNESSEE Vanderbilt Univ Med Ctr Division of Infectious Diseases / 345 24th Avenue North Nashville, TN 37203 Victoria Harris (615)467-0154 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 (310)478-3711 Recruiting 000524. DISTRICT OF COLUMBIA Washington DC VA Medical Center 50 Irving Street NW / 151B Washington, DC 20422 Barbara Standridge (202)745-8695 Recruiting 000509. FLORIDA Miami Veterans Administration Med Ctr 1201 Northwest 16th St Miami, FL 33125 Mack Smith (305)324-3267 Recruiting 000707. GEORGIA Atlanta VA Med Ctr 1670 Clairmont Rd Mailstop RIM-111 Decatur, GA 30033 Susan Wirtz (404)321-6111 Recruiting 001017. ILLINOIS VA Chicago Health Care System - West Side Div 820 South Damen Ave Chicago, IL 60612 Mary Jo Werhane (312)666-6500 Recruiting 000614. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd Chicago, IL 60657 Rita Verheggen (773)244-5800 Recruiting 010404. MARYLAND Natl Naval Med Ctr 8901 Wisconsin Ave Bethesda, MD 208995000 Jean Vita (301)295-6400 Recruiting 001130. MARYLAND Warren G Magnuson Clinical Ctr Patient Recruitment & Public Liaison Office / Bldg 61 Bethesda, MD 208924754 Patient Recruitment (800)411-1222 Recruiting 000310. MINNESOTA Abbott-Northwestern Hosp / Clinic 42 2545 Chicago Ave South Minneapolis, MN 55404 Joann Armstrong (612)863-5336 Recruiting 000509. NEW JERSEY Infectious Disease Specialists of NJ 1308 Morris Ave / Suite 204 Union, NJ 07083 Philip Andrew (908)810-9200 Recruiting 001019. OREGON The Research & Education Group 1650 NW Naito Parkway Portland, OR 97209 Norma Martinez (503)229-8428 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 (453)632-3021 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 (661)344-6180 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 (472)211-9112 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 (458)949-1802 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 (468)616-3476 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 (453)545-7752 Recruiting 000509. OTHER Haven Program Laurentian Hosp Sudbury Regional Hosp Laurentian Site / 41 Ramsey Lake Rd Sudburg, Judy Latendre-Paquette (705)523-7059 Recruiting 000719. OTHER Aalborg Hosp South Dept of Infectious Diseases Aalborg, Carsten Larsen (459)932-3205 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 (416)340-3871 Recruiting 001012. OTHER McMaster Univ Med Centre 1200 Main St West / Rm 2F41 Hamilton, ON Sherie Savoy (905)521-2100 Recruiting 000707. OTHER Windsor Regional Hosp HIV Care Program / 1995 Lens Ave Windsor, ON Nancy McFarland (519)254-6115 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 (819)829-3230 Recruiting 001012. OTHER Montreal Chest Institute 3650 Saint Urbain St Montreal , QC Sabrina Mastroprimiano (514)849-5201 Recruiting 000824. OTHER Centre Hospitalier Universitaire de Quebec Pavillon CHUL / Rm S-745 / 2705 Boul Laurier Ste-Foy, QC Lyne Lapointe (418)656-4141 Recruiting 000824. TEXAS Montrose Clinic 215 Westheimer Rd Houston, TX 77006 Brian Bell (713)830-3011 Recruiting 000509. TEXAS Houston Veterans Administration Med Ctr 2002 Holcombe Blvd Houston, TX 77030 Katharine Breaux (713)794-7943 Recruiting 000509. TEXAS South Texas Veterans Health Care System 7400 Merton Minter Blvd San Antonio, TX 78284 Kimberly Summers (210)949-3076 Recruiting 000524. TEXAS Univ TX Health Science Ctr 6431 Fannin St Houston, TX 77030 Hilda Cuervo (713)500-6751 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 (800)411-1222 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 (800)411-1222 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 (205)975-7925 Recruiting 000403. CALIFORNIA Marin County Specialty Clinic 161 Mitchell Building Suite 200 San Rafael, CA 94903 Marc Gould (415)476-9296 Recruiting 000310. CALIFORNIA Univ of California / San Diego Treatment Ctr 2760 5th Ave / Suite 300 San Diego, CA 921036325 Jill Kunkel (619)543-8080 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 (323)343-8283 Recruiting 010717. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 Recruiting 000310. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 Recruiting 001031. COLORADO Denver Dept of Health and Hosps 4200 East 9th Ave / Campus Box B-196 Denver, CO 80262 M Graham Ray (303)372-5535 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 (303)372-5535 Recruiting 000310. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3841 No longer recruiting 000621. ILLINOIS Cook County Hosp 637 South Wood Chicago, IL 60612 Edward Goodwin (312)572-4545 No longer recruiting 001005. INDIANA Methodist Hosp of Indiana / Life Care Clinic 1633 North Capital Ave Indianapolis, IN 46202 Sarah Ryan (317)929-2917 Recruiting 000112. INDIANA Division of Inf Diseases/ Indiana Univ Hosp 1001 West 10th St / OPW 430 Indianapolis, IN 46202 Beth Zwickl (317)274-8456 Recruiting 000112. INDIANA Indiana Univ Hosp 550 North Univ Blvd / Room 0674 Indianapolis, IN 462025250 Beth Zwickl (317)274-8456 Recruiting 000112. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Rebecca Becker (410)955-4370 Recruiting 010723. MINNESOTA Univ of Minnesota 420 Delaware St SE / PO Box 437 Minneapolis, MN 55455 Christine Fietzer (612)625-1462 Recruiting 000203. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Barbara Longmire (919)966-7883 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 (212)263-6565 Recruiting 000112. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 001012. NEW YORK Chelsea Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St New York, NY 10021 Brenda Greenhill (212)746-4177 Recruiting 000524. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 000817. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 000112. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Brenda Greenhill (212)746-4177 Recruiting 000419. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 Recruiting 000515. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 000515. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 Recruiting 000509. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 001110. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 001012. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 No longer recruiting 001121. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 001110. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (410)614-1921 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 (205)458-8700 Recruiting 000819. CALIFORNIA St Lukes Medical Group 1855 First Ave San Diego, CA 92101 Rebecca Gonzalez (619)235-0501 Recruiting 000818. CALIFORNIA Pacific Oaks Research 8641 Wilshire Blvd Beverly Hills, CA 90211 Brenda Perry (310)652-2562 Recruiting 000818. CALIFORNIA Kaiser Foundation Hospital 4141 Geary Blvd / Suite 219 San Francisco, CA 94118 Mary Beth Charland (415)202-3480 Recruiting 000818. CALIFORNIA Orange County Ctr for Special Immunology 11190 Warner Ave / Suite 411 Fountain Valley, CA 92708 Tonya Rhoads (714)751-5800 Recruiting 000818. COLORADO Denver Inf Disease Consultants 4545 E 9th Ave / Suite 120 Denver, CO 80220 Cheryl Stewart (303)393-8050 Recruiting 000818. DISTRICT OF COLUMBIA Dupont Circle Physicians Group 1737 20th St NW Washington, DC 200091104 Linda Green (202)745-0201 Recruiting 000818. FLORIDA Steinhart Medical Associates 3659 South Miami Ave / Suite 4006 Miami, FL 33133 Amy S Liebmann (305)856-2171 Recruiting 991026. FLORIDA Specialty Med Care Ctrs of South Florida Inc 1313 NW 36th St Miami, FL 33142 Maria Paredes (305)634-7700 Recruiting 000818. FLORIDA Community AIDS Resource Inc 1320 South Dixie Hwy Coral Gables, FL 33146 Christiane Jones (305)661-1150 Recruiting 000818. ILLINOIS Northstar Med Clinic 2835 North Sheffield Ave Chicago, IL 60657 Matt Sirinek (773)296-2400 Recruiting 000818. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd #108 Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting 000814. MASSACHUSETTS Fenway Community Health Ctr 7 Haviland St Boston, MA 02115 Lorraine Schieve (617)927-6075 Recruiting 000818. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Candy Tobin (973)483-3444 Recruiting 000818. NEW YORK Anderson Clinical Research Inc 97-45 Queens Blvd / 12th Floor Rego Park, NY 11374 Yolanda Sipin (718)896-2500 Recruiting 000818. NEW YORK Albany Med College 47 New Scotland Ave / MC 142 Albany, NY 12208 Sandra Preston (518)262-6330 Recruiting 000818. OKLAHOMA Associates in Med and Mental Health 2325 S Harvard / Suite 600 Tulsa, OK 74114 Jennifer Dunn (918)743-1000 Recruiting 000818. OREGON Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 Recruiting 000818. PENNSYLVANIA Anderson Clinical Research 225 Penn Ave Pittsburgh, PA 15221 John Meneski (412)247-2292 Recruiting 000818. TEXAS N Texas Ctr for AIDS & Clin Rsch 3514 Cedar Springs Rd / Suite 200 Dallas, TX 75219 Kathy Hanks (214)520-1810 Recruiting 000818. TEXAS Central Texas Clinical Research 1015 East 32nd Street / Suite 215 Austin, TX 78705 Peggy Wright (512)480-9660 Recruiting 000818. TEXAS Joseph Gathe Private Practice 1200 Binz St / Suite 120 Houston, TX 77004 Jennifer Welch (713)526-9821 Recruiting 000818. WASHINGTON Virginia Mason Med Ctr 1100 9th Ave Seattle, WA 98101 Cheryl Weaver (206)223-6835 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 (619)543-8080 Recruiting 991115. TEXAS Univ of Texas Southwestern Med Ctr 5323 Harry Hines Blvd Dallas, TX 75235 Phillip Keiser (214)590-5182 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 (619)543-8080 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 (619)543-8080 Recruiting 991115. CALIFORNIA Cedars Sinai Med Ctr 8700 Beverly Blvd / B-217 / AIDS and Immune Disorders Center Los Angeles, CA 90048 Dr Eric Darr (310)855-3896 Recruiting 991115. CALIFORNIA San Francisco Gen Hosp / UCSF AIDS Program 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 94110 Dr. Jim Kahn (415)476-4082 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 (619)543-8080 Recruiting 991115. CALIFORNIA Cedars Sinai Med Ctr 8700 Beverly Blvd / B-217 / AIDS and Immune Disorders Center Los Angeles, CA 90048 Dr Eric Darr (310)855-3896 Recruiting 991115. CALIFORNIA San Francisco Gen Hosp / UCSF AIDS Program 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 94110 Dr. Jim Kahn (415)476-4082 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 (415)476-9554 Recruiting 991019. COLORADO Denver CPCRA / Denver Public Hlth 605 Bannock St Denver, CO 802044507 Jack Rouff (303)436-7184 Recruiting 991019. CONNECTICUT Yale Univ School of Medicine / AIDS Program 135 College St / Suite 323 New Haven, CT 06510 Laurie Andrews (203)785-3557 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 (202)745-8301 Recruiting 991019. GEORGIA AIDS Research Consortium of Atlanta 131 Ponce de Leon Ave / Suite 130 Atlanta, GA 303081962 Melanie Thompson MD (404)876-2317 No longer recruiting 010528. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd #108 Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting 991019. LOUISIANA Louisiana Comm AIDS Rsch Prog / Tulane Univ Med 1430 Tulane Ave / TB 21 New Orleans, LA 70112 Janice Walker (504)584-1971 Recruiting 991019. MICHIGAN Henry Ford Hosp 2799 West Grand Blvd / CFP-104 Detroit, MI 48202 Diane Mastro-Polak (313)876-2798 Recruiting 991019. MICHIGAN Wayne State Univ - WSU/DMC / Univ Hlth Ctr 4201 Saint Antoine / POD 7C Detroit, MI 48201 Jan Kosmyna (313)993-0923 Recruiting 991019. NEW JERSEY Southern New Jersey AIDS Clinical Trials Dept of Medicine / 3 Cooper Plaza / Suite 513 Camden, NJ 08103 Carol Graeber (856)963-6890 Recruiting 991019. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Robert C Sawyer (973)483-3444 Recruiting 991019. NEW MEXICO Partners in Research / New Mexico 915 Camino de Salud NE Albuquerque, NM 87131 Cynthia Nicholson (505)272-6501 Recruiting 991019. NEW YORK Bronx-Lebanon Hosp Ctr Vaccine Trial Site / 1645 Grand Concourse Suite 1G Bronx, NY 10453 Elizabeth Doramajian (718)901-6346 Recruiting 010119. NEW YORK Harlem AIDS Treatment Grp / Harlem Hosp Ctr 506 Lenox Ave / Rm 3101A New York, NY 10037 Luis Fuentes (212)939-2957 Recruiting 991019. OREGON The Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 Recruiting 991019. PENNSYLVANIA Philadelphia FIGHT 1233 Locust St / 5th Floor Philadelphia, PA 19107 Jane Shull (215)985-4448 Recruiting 991019. TEXAS Univ TX Health Science Ctr 6431 Fannin St Houston, TX 77030 Hilda Cuervo (713)500-6751 Recruiting 001114. VIRGINIA Richmond AIDS Consortium / Div of Infect Diseases PO Box 980049 Richmond, VA 232980049 Vinnie Mitchell (757)828-2477 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 (205)975-7925 Recruiting 010103. CALIFORNIA Univ of California San Diego UCSD Treatment Center / 150 West Washington St Suite 100 San Diego, CA 92103 Jill Kunkel (619)543-8080 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 (303)372-5535 Recruiting 010103. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 010318. MASSACHUSETTS Beth Israel Deaconess - West Campus One Deaconess Rd / Kennedy Building 6th Floor Boston, MA 02215 Helen Fitch (617)632-0785 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 (314)454-0058 Recruiting 010103. NORTH CAROLINA Duke Univ Med Ctr Hosp South / PO Box 3284 Durham, NC 27710 Paulette MacDougall (919)668-0161 Recruiting 010207. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 010103. TEXAS Univ of Texas Galveston AIDS Clinical Trials Unit / 301 University Blvd Galveston, TX 775550435 Karen Waterman (409)772-0361 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 (415)554-9065 Recruiting 991122. COLORADO Denver Dept of Public Health / HIVNET 605 Bannock St / Room 220 Denver, CO 80204 Frank Judson (303)436-7208 Recruiting 991122. ILLINOIS Univ of Illinois Chicago / Howard Brown Hlth Ctr Division of Infectious Diseases / 808 South Wood St Chicago, IL 60612 Fred Swanson (773)388-8884 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 (617)267-1831 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 (212)263-6068 Recruiting 991122. PENNSYLVANIA Univ of Pennsylvania / HIVNET RAP Office / 521-523 West Girard Ave Philadelphia, PA 19104 Cynthia Clark (215)236-9511 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 (617)267-1831 Recruiting 991122. WASHINGTON Univ of Washington 901 Boren Ave Suite 1300 UW Box 3599227 Seattle, WA 98104 Dennis Torres (206)521-5812 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 (415)554-9183 Recruiting 991018. ILLINOIS Univ of Illinois Chicago / Howard Brown Hlth Ctr Division of Infectious Diseases / 808 South Wood St Chicago, IL 60612 Fred Swanson (773)388-8884 Recruiting 991018. MASSACHUSETTS Fenway Community Health Ctr / HIVNET 7 Haviland St Boston, MA 02115 Lorraine Schieve (617)927-6400 Recruiting 000509. MINNESOTA Univ of Minnesota 420 Delaware St SE / Box 250 Minneapolis, MN 55455 Chuck Sieber (612)625-9984 Recruiting 000404. NEW YORK Bronx-Lebanon Hosp Ctr Vaccine Trial Site / 1645 Grand Concourse Suite 1G Bronx, NY 10453 Elizabeth Doramajian (718)901-6346 Recruiting 991018. NEW YORK New York Univ Med Ctr 650 First Ave 5th Floor New York, NY 10016 Cynthia Harrison (212)263-0344 Recruiting 991018. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 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 (401)729-3292 Recruiting 991018. WASHINGTON Fred Hutchinson Cancer Research Ctr 1100 Fairview Ave N / PO Box 19024 Seattle, WA 98109 Theresa Shea (206)720-4340 Recruiting 991018. WASHINGTON Univ of Washington 901 Boren Ave Suite 1300 UW Box 3599227 Seattle, WA 98104 Manuel Ramirez (206)521-1203 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 (205)458-8700 Recruiting 990708. ARIZONA Body Positive 4021 N 30th St Phoenix, AZ 85016 Barbara Kasimir (602)955-4673 Recruiting 990708. CALIFORNIA AIDS Healthcare Foundation 1300 North Vermont Ave Los Angeles, CA 900276069 Euny Kim (323)913-3953 Recruiting 990708. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave San Francisco, CA 94115 Dorie Heeren (415)476-9296 Recruiting 990708. FLORIDA County Line Med CtrInc 4065 SW 40th Ave Pembrook, FL 33023 Dennis Rosa-Re (954)893-5800 Recruiting 990708. FLORIDA Dr Gerald Pierone Jr 3715 7th Terrace Vero Beach, FL 32960 Jeff Mieras (561)978-9556 Recruiting 990708. FLORIDA Med Alternatives 2480 East Commercial Blvd / Suite #2 Fort Lauderdale, FL 33308 Fausto Capella (954)776-1240 Recruiting 990708. ILLINOIS The CORE Ctr 2020 West Harrison St Chicago, IL 60612 Marisol Gonzalez (312)572-4577 Recruiting 990708. INDIANA Indiana Univ Med Ctr 550 N Univ Blvd / Room 5550 Indianapolis, IN 462025250 Beth Zwickle (317)274-8456 Recruiting 990708. KANSAS Univ of Kansas School of Medicine 1010 North Kansas St Wichita, KS 672143124 Janice Cerrulo (316)293-2617 Recruiting 990708. MICHIGAN Henry Ford Hosp Div of Infect Diseases / 2799 West Grand Blvd / CFP 106 Detroit, MI 48202 Diane Smith (313)876-1132 Recruiting 990708. NEW HAMPSHIRE Dartmouth-Hitchcock Med Ctr 1 Med Ctr Dr / Clinic 3D Lebanon, NH 03756 Donna Alvarenga (603)650-5438 Recruiting 990708. NEW JERSEY Infectious Disease Assoc of Central Jersey 411 Courtyard Dr Somerville, NJ 08876 Larry Hocking (908)725-2522 Recruiting 990708. NEW JERSEY NJCRI 393 Central Ave / Suite 301 Newark, NJ 07103 Kerry Gristi (973)483-3444 Recruiting 990708. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 Recruiting 990708. OTHER Clinique Medicale du Quartier Latin 905 Boul Rene Levesque Est Montreal, QC Denise LaFreniere (514)285-5500 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 (514)524-3642 Recruiting 990708. PENNSYLVANIA Anderson Clinical Research 3339 Ward St Pittsburgh, PA 15213 Monica Earnest (800)711-5878 Recruiting 990708. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75235 Claudia Quittner (214)648-9296 Recruiting 990708. TEXAS Montrose Clinic 215 Westheimer Rd Houston, TX 77006 Barbara Buckhardt (713)830-3013 Recruiting 990708. TEXAS Joseph Gathe Private Practice 1200 Binz St / Suite 120 Houston, TX 77004 Dorothy Bartley (281)459-1549 Recruiting 990708. VIRGINIA Hampton Roads Med Specialists 2112 Executive Dr Hampton, VA 23666 Lois Hulman (757)838-8677 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 (317)274-8456 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 (212)263-6565 Recruiting 990930. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 No longer recruiting 001219. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 991015. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 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 (205)558-2328 Recruiting 000419. ARIZONA Phoenix Childrens Hosp 909 East Brill Street Phoenix, AZ 85006 Laura Clarke-Steffan (602)239-5261 Recruiting 000914. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 000225. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 000225. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 000225. CALIFORNIA Los Angeles County - USC Med Ctr 1640 Marengo St Los Angeles, CA 90033 Eva Operskalski (323)226-2342 Recruiting 000614. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 001116. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 Recruiting 000225. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Susan Zamer (202)884-2837 Recruiting 000225. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 000228. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 010109. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 000726. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 010109. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 Recruiting 000228. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 000225. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000225. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 000225. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 000914. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 000225. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 000524. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 000225. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 Recruiting 000228. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Silvia Callejas (732)235-7382 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 (973)972-3118 No longer recruiting 010402. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 000225. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000524. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 No longer recruiting 010528. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 000228. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000524. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 000614. NEW YORK New York Hosp - Cornell Med Ctr 505 East 70th St New York, NY 10021 Anne Monroe (212)746-3367 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 (516)444-1313 Recruiting 000225. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 000225. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 000225. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 000225. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 000225. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 000225. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 000225. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 Recruiting 000225. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 000829. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 Recruiting 000225. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (205)558-2328 No longer recruiting 010227. ALABAMA Univ of South Alabama 1504 Springhill Avenue Mobile, AL 36604 Julie Bebawy (334)405-5107 Recruiting 990913. CALIFORNIA Harbor - UCLA Med Ctr / UCLA School of Medicine 1000 West Carson Blvd Los Angeles, CA 905022004 Zane O'Keefe (310)206-6369 Recruiting 991118. CALIFORNIA Cedars Sinai / UCLA Med Ctr 8700 Beverly Boulevard Los Angeles, CA 900481804 Zane O'Keefe (310)206-6369 No longer recruiting 010410. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 No longer recruiting 000912. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 990930. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 No longer recruiting 000817. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Susan Zamer (202)884-2837 Recruiting 990908. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 991025. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 990930. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Deanna Cruz (954)728-8080 Recruiting 010406. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 991202. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 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 (773)257-6930 Recruiting 000424. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 990730. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 991129. LOUISIANA Tulane Univ Hosp of New Orleans 1430 Tulane Ave New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 991014. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 990914. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 991227. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 990730. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 990930. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 990813. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 000310. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Silvia Callejas (732)235-7382 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 (973)972-3118 Recruiting 000310. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 990903. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 Recruiting 991129. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 991129. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 991202. NEW YORK Children's Hosp at Albany Med Ctr 47 New Scotland Ave / A-111 Albany, NY 12208 Mary Ellen Adams (518)262-6888 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 (516)444-1313 Recruiting 991102. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 No longer recruiting 000727. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 No longer recruiting 001110. NEW YORK Montefiore Med Ctr Adolescent AIDS Program 111 East 210th St Bronx, NY 10467 Dina Monte (718)882-0023 No longer recruiting 000725. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 991124. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 990903. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 991025. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 991129. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 No longer recruiting 000817. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 990928. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (205)558-2328 Recruiting 990930. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 010228. FLORIDA Sacred Heart Children's Hosp / CMS of Florida 5192 Bayou Blvd Pensacola, FL 32503 Susan Wilson (850)484-5040 Recruiting 001110. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 000515. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 010418. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000424. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 991208. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 991012. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 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 (973)972-3118 Recruiting 001012. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000726. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 Recruiting 990924. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 991129. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 000621. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000726. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 990913. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 000726. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 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 (415)353-0800 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 (650)852-3408 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 (760)864-6266 No longer recruiting 000807. ILLINOIS Northwestern Univ Med School 303 East Superior St / Passavant Pavilion Chicago, IL 60611 Jon Stanford (312)908-0949 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 (212)604-2246 Recruiting Enrollment for only Group 4 is open. 010625. TEXAS Plaza Med Ctr 1200 Binz St Houston, TX 77004 Dorothy Bartley (713)526-9821 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 (619)543-8080 Recruiting 991209. CALIFORNIA Stanford Univ Med Ctr 300 Pasteur Dr / S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 001219. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 Recruiting 990707. CALIFORNIA San Mateo AIDS Program / Stanford Univ 300 Pasteur Drive / Room S-156 Stanford, CA 943055107 Debbie Slamowitz (650)723-2804 Recruiting 001219. CALIFORNIA Willow Clinic 795 Willow Rd Menlo Park, CA 94025 Debbie Slamowitz (650)723-2804 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 (303)372-5535 Recruiting 000419. ILLINOIS Northwestern Univ Med School 676 N St Clair / Suite 200 Chicago, IL 60611 Baiba L Berzins (312)695-5012 Recruiting 000228. MARYLAND Johns Hopkins Hosp 1830 East Monument St / Room 8074 Baltimore, MD 21287 Rebecca Becker (410)955-4370 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 (212)263-6565 Recruiting 990809. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 001012. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 Recruiting 000629. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 991109. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 991208. OHIO Univ of Cincinnati Eden and Albert Sabin Way Cincinnati, OH 452670405 Tammy Powell (513)584-8373 No longer recruiting 010115. OHIO Ohio State Univ Hosp Clinic 456 West 10th Ave / Room 4725 Columbus, OH 432101228 Judith Neidig (614)293-8112 No longer recruiting 010213. OHIO MetroHealth Med Ctr 2500 MetroHealth Dr Cleveland, OH 441091998 Richard McVey (216)778-5489 Recruiting 000824. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 001006. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 Recruiting 991208. PENNSYLVANIA Univ of Pittsburgh 7th Floor Falk Clinic / 200 Lothrop Street Pittsburgh, PA 15213 Christine Tripoli (412)647-0771 No longer recruiting 010522. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 000419. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 Recruiting 001024. SOUTH CAROLINA Julio Arroyo 206 Medical Circle / Suite 2A West Columbia, SC 29169 Michael Klebert (314)454-0058 Recruiting 990830. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd Dallas, TX 75390 Charla Andrews (214)590-0414 Recruiting 010118. WASHINGTON Univ of Washington Harborview Med Ctr / 325 9th Ave Box 359929 Seattle, WA 98104 Jeanne Conley (206)731-8877 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 (415)476-9554 Recruiting 990804. COLORADO Denver CPCRA / Denver Public Hlth 605 Bannock St Denver, CO 802044507 Jack Rouff (303)436-7184 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 (202)745-8301 Recruiting 990804. GEORGIA AIDS Research Consortium of Atlanta 131 Ponce de Leon Ave / Suite 130 Atlanta, GA 303081962 Melanie Thompson MD (404)876-2317 No longer recruiting 010528. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd #108 Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting 990804. LOUISIANA Louisiana Comm AIDS Rsch Prog / Tulane Univ Med 1430 Tulane Ave / TB 21 New Orleans, LA 70112 Janice Walker (504)584-1971 Recruiting 990804. MICHIGAN Henry Ford Hosp 2799 West Grand Blvd / CFP-104 Detroit, MI 48202 Diane Mastro-Polak (313)876-2798 Recruiting 990804. MICHIGAN Wayne State Univ - WSU/DMC / Univ Hlth Ctr 4201 Saint Antoine / POD 7C Detroit, MI 48201 Jan Kosmyna (313)993-0923 Recruiting 990804. NEW JERSEY Southern New Jersey AIDS Cln Trials / Dept of Med 3 Cooper Plaza / Suite 220 Camden, NJ 08103 Maryann LiVolsi (609)963-6890 Recruiting 990804. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Robert C Sawyer (973)483-3444 Recruiting 990804. NEW MEXICO Partners in Research / New Mexico 915 Camino de Salud NE Albuquerque, NM 87131 Cynthia Nicholson (505)272-6501 Recruiting 990804. NEW YORK Harlem AIDS Treatment Grp / Harlem Hosp Ctr 506 Lenox Ave / Rm 3101A New York, NY 10037 Luis Fuentes (212)939-2957 Recruiting 990804. OREGON The Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 Recruiting Includes Vancouver Canada area. 990804. PENNSYLVANIA Philadelphia FIGHT 1233 Locust St / 5th Floor Philadelphia, PA 19107 Jane Shull (215)985-4448 Recruiting 990804. VIRGINIA Richmond AIDS Consortium / Div of Infect Diseases PO Box 980049 Richmond, VA 232980049 Vinnie Mitchell (757)828-2477 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 (205)975-7925 Recruiting 990910. CALIFORNIA San Francisco Gen Hosp / AIDS Division 995 Potrero Ave Bldg 80 San Francisco, CA 94110 Rosaleen Brennan (415)476-9296 Recruiting 991019. CALIFORNIA Saint Francis Mem Hosp 900 Hyde St San Francisco, CA 94109 Lois Hillman (415)353-6218 Recruiting 990910. CALIFORNIA Harbor UCLA Med Ctr 1124 West Carson St Torrance, CA 90502 Petra Miller (310)222-3848 Recruiting 990910. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Judy Carden (310)825-1301 Recruiting 991021. CALIFORNIA Univ of Southern California SP21 Rand Schrader Clinic / 1300 N Mission Rd Rm 349 Los Angeles, CA 90033 Irene Teran (323)343-8278 Recruiting 000622. CALIFORNIA Santa Clara Valley Med Ctr 751 South Bascom Ave San Jose, CA 95128 Arthi Chakravarthy (650)364-6563 Recruiting 000905. CALIFORNIA Kaiser Foundation Hospital 4141 Geary Blvd / Suite 219 San Francisco, CA 94118 Mary Beth Charland (415)202-3223 Recruiting 990910. CALIFORNIA Orange Coast Med Group 361 Hosp Rd Suite 126 Newport Beach, CA 92663 Tony Navarro (949)646-1111 Recruiting 990910. CALIFORNIA East Bay AIDS Ctr 2850 Telegraph Ave Berkeley, CA 94705 Lucinda Hopewell (510)204-1291 Recruiting 000905. CONNECTICUT Yale New Haven Hosp / Nathan Smith Clinic 15 York St New Haven, CT 06504 Cindy Frank (203)785-6939 Recruiting 990910. DISTRICT OF COLUMBIA Georgetown Univ Med Ctr 3800 Reservoir Rd NW / 110 Kober-Cogan Building Washington, DC 20007 Melanie Cordoro (202)687-7387 Recruiting 991019. DISTRICT OF COLUMBIA Veterans Administration Med Ctr 50 Irving St NW Washington, DC 20422 Charlotte Mauzy (202)745-8000 Recruiting 990910. FLORIDA Treasure Coast Infectious Disease Consultants 3715 7th Terrace Vero Beach, FL 32960 Jeff Mieras (561)978-9556 Recruiting 000522. FLORIDA Community AIDS Resource Inc 1320 South Dixie Hwy Coral Gables, FL 33146 Christiane Jones (305)661-1150 Recruiting 990910. GEORGIA AIDS Research Consortium of Atlanta Inc 131 Ponce de Leon Ave Atlanta, GA 30308 Nicole Miller (404)876-2317 Recruiting 990910. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting 990910. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr / Rush Med Coll 1653 West Congress Parkway 1577 Jelke Chicago, IL 60612 Danielle Merten (312)942-5000 Recruiting 991019. ILLINOIS Northwestern Univ Med School 303 E Superior St Chicago, IL 60611 Ann McCord (312)926-8358 Recruiting 990910. INDIANA Indiana Univ Hosp 550 North Univ Blvd Indianapolis, IN 462025250 Helen Romiger (317)274-8456 Recruiting 001207. MICHIGAN Henry Ford Hosp 2799 West Grand Blvd Detroit, MI 48202 Linda Makohon (313)916-2570 Recruiting 990910. MISSOURI Washington Univ School of Med 5535 Delmar Blvd St Louis, MO 63112 Mike Conklin (314)879-6412 Recruiting 001021. NORTH CAROLINA Duke Univ Med Ctr / Infectious Disease Clinic South Hosp Box 3306 / Trent Dr Durham, NC 27710 Meg McDaniel (919)668-0164 Recruiting 990910. NORTH CAROLINA Univ of North Carolina Burnett - Womack Bldg / CB #7215 Chapel Hill, NC 275997215 Laurie Frarey (919)843-8765 Recruiting 000920. NEW MEXICO Univ of New Mexico Health Science Center 2211 Lomas Blvd NE Albuquerque, NM 87131 Cynthia Nicholson (505)272-6501 Recruiting 991019. NEW YORK Howard A Grossman MD 155 West 19th St 4th Floor New York, NY 10011 Howard A. Grossman (212)929-2629 Recruiting 000522. NEW YORK New York Univ Med Ctr 550 First Ave New York, NY 10016 Richard Hutt (212)263-6565 Recruiting 990910. NEW YORK Liberty Medical 314 West 14th St / 4th Floor New York, NY 10014 Debbie Goldman (212)995-6907 Recruiting 001005. NEW YORK Beth Israel Med Ctr 350 E 17th St New York, NY 10003 Ann Marshak (212)420-4519 Recruiting 990910. OHIO Ohio State Univ Med Ctr 456 West 10th Ave Columbus, OH 43210 Judith Neidig (614)293-8112 Recruiting 991019. OHIO Univ Hosps of Cleveland 2061 Cornell Rd / Foley Building Cleveland, OH 44106 Ann Conrad (216)844-3259 Recruiting 990910. OKLAHOMA Associates in Med and Mental Health 2325 South Harvard / Suite 600 Tulsa, OK 74114 Sheila Stafford (918)743-1006 Recruiting 990910. PENNSYLVANIA Bornemann Internal Medicine 145 N 6th Street / Suite 205 Reading , PA 19601 Paula Shivers (610)378-2552 Recruiting 000718. PENNSYLVANIA Hershey Med Ctr 500 Univ Dr Hershey, PA 17033 Kathleen Hay (717)531-4213 Recruiting 990910. PENNSYLVANIA Univ of Pittsburgh Med Ctr 200 Lothrop St Pittsburgh, PA 15213 Nancy Mantz (412)647-8125 Recruiting 990910. TEXAS Univ of Texas / Med School at Houston 6431 Fannin Houston, TX 77030 Hilda Cuervo (713)500-6751 Recruiting 990910. TEXAS Univ of Texas Med Branch 301 University Blvd Galveston, TX 77555 Cheryl Mogridge (409)747-0241 Recruiting 990910. TEXAS South Texas Veterans Health Care System 7400 Merton Minter Blvd San Antonio, TX 78284 Juan Toro (210)617-5300 Recruiting 990910. VIRGINIA Richmond AIDS Consortium 1001 East Broad St Richmond, VA 23219 Patricia Dodson (804)828-3450 Recruiting 990910. WISCONSIN Univ of Wisconsin 600 Highland Ave #6/368 Madison, WI 53792 Shelly Beckwith (608)265-5729 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 (205)458-8700 Recruiting 990527. ALABAMA Univ of Alabama at Birmingham 1917 Clinic / 908 South 20th St Birmingham, AL 35294 Wanda Ball (205)934-9657 Recruiting 990527. CALIFORNIA UCSF - San Francisco Gen Hosp 635 Potrero Ave San Francisco, CA 94110 Nelson Murcar (415)476-9296 Recruiting 990527. CALIFORNIA UCSD Treatment Ctr 2760 5th Ave / Suite 300 San Diego, CA 92103 Francesca Torriani M.D. (619)543-8080 Recruiting 990527. COLORADO Univ of Colorado / Health Science Ctr 4200 E Ninth Ave Denver, CO 80262 Graham Ray (303)315-7233 Recruiting 990527. DISTRICT OF COLUMBIA ViRx / Dupont Circle Physicians Group 1737 20th St NW Washington, DC 20009 Linda Green (202)745-0201 Recruiting 990527. GEORGIA AIDS Research Consortium of Atlanta 131 Ponce de Leon Ave NE / Suite 130 Atlanta, GA 30308 Paul Couey (404)876-2317 Recruiting 990527. ILLINOIS Rush Presbyterian - Saint Luke's Med Ctr 600 South Paulina St Chicago, IL 60612 Nancy Hussa (312)942-5865 Recruiting 990527. MISSOURI Washington Univ School of Medicine 4511 Forest Park / Suite 304 St Louis, MO 63108 Michael Klebert (314)454-0058 Recruiting 990527. NEW YORK Beth Israel Med Ctr Division of Infectious Diseases / 350 East 17th St New York, NY 10003 Ann Marshak (212)420-4519 Recruiting 990527. NEW YORK Columbia Presbyterian Med Ctr Harkness Pavilion 6 Room 644 / 622 West 168th Street New York, NY 10032 Mykyelle Crawford (212)305-7897 Recruiting 990527. NEW YORK Albany Med College 47 New Scotland Ave / MC 142 Albany, NY 12208 Sandra Preston (518)262-6970 Recruiting 990527. OHIO Case Western Reserve Univ Foley Bldg / 2061 Cornell Rd Cleveland, OH 44106 Michael Chance (216)844-8051 Recruiting 990527. OTHER Ottawa General Hospital 501 Smyth Rd / Room G12 Ottawa, ON Nanci Hawley-Foss (613)737-8879 Recruiting 990527. TEXAS Univ TX Galveston Med Branch 301 University Blvd Galveston, TX 77555 Phyllis Galatas (409)747-0241 Recruiting 990527. TEXAS Oak Lawn Physicians Group 3514 Cedar Springs Rd / Suite 200 Dallas, TX 75219 Joe Cheatum (214)520-1810 Recruiting 990527. TEXAS Univ of Texas Southwestern Med Ctr of Dallas 5323 Harry Hines Blvd / Building K1 900 Dallas, TX 75235 Sandra Tanksley (214)648-3246 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 (619)543-8080 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 (323)343-8283 Recruiting 990811. CALIFORNIA San Francisco Gen Hosp 995 Potrero Ave / Building 80 / Ward 84 San Francisco, CA 941102859 Marc Gould (415)476-9296 Recruiting 990719. CALIFORNIA UCLA CARE Ctr 10833 Le Conte Ave / BH 412 - CHS Los Angeles, CA 90095 Susan McCarthy (310)206-8029 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 (303)372-5535 Recruiting 000829. FLORIDA Univ of Miami School of Medicine 1800 Northwest 10th Ave / P O Box 016960 Miami, FL 331361013 Leslie Thompson (305)243-3841 No longer recruiting 010402. HAWAII Univ of Hawaii 3675 Kilauea Ave / Leahi Hosp / Young Building 5th Floor Honolulu, HI 96816 Debra Ogata-Arakaki (808)737-2751 Recruiting 990730. MASSACHUSETTS Harvard (Massachusetts Gen Hosp) 55 Fruit St / Founders Bldg 8th Floor Boston, MA 02114 Teri Flynn (617)726-3819 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 (212)263-6565 Recruiting 990623. NEW YORK Columbia Presbyterian Med Ctr 180 Fort Washington Ave / Harkness Pavilion New York, NY 10032 Mykyelle Crawford (212)305-2665 Recruiting 001012. NEW YORK Mount Sinai Med Ctr One Gustave Levy Place / PO Box 1042 New York, NY 10029 Eileen Chusid (212)241-0433 No longer recruiting 010227. NEW YORK Chelsea Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St New York, NY 10021 Brenda Greenhill (212)746-4177 No longer recruiting 000502. NEW YORK Beth Israel Med Ctr First Ave at 16th St / 19 Baird Hall New York, NY 10003 Ann Marshak (212)420-4432 Recruiting 990812. NEW YORK Univ of Rochester Medical Center 601 Elmwood Ave Rochester, NY 14642 Carol Greisberger (716)275-5871 Recruiting 990730. NEW YORK Cornell Univ Med Ctr Cornell Univ Clinical Trials Unit / 525 East 68th St / ACTG BoxNew York, NY 10021 Brenda Greenhill (212)746-4177 No longer recruiting 000502. OTHER Univ of Puerto Rico PO Box 365067 San Juan, PR 009365067 Virginia Ramirez (787)767-9192 No longer recruiting 010501. PENNSYLVANIA Univ of Pennsylvania at Philadelphia 536 Johnson Pavilion / 3600 Hamilton Walk Philadelphia, PA 19104 Christopher Helker (215)349-8092 Recruiting 000210. RHODE ISLAND Miriam Hosp / Brown Univ 164 Summit Ave Providence, RI 02906 Joan Gormley (401)793-4396 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 (205)558-2328 Recruiting 000817. CALIFORNIA Harbor - UCLA Med Ctr / UCLA School of Medicine 1000 West Carson Blvd Los Angeles, CA 905022004 Zane O'Keefe (310)206-6369 Recruiting 000817. CALIFORNIA Children's Hosp of Oakland 747 52nd St Oakland, CA 946091809 Teresa Courville (510)428-3885 Recruiting 000817. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 000817. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 000817. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 000817. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 Recruiting 000817. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Maryanne Dillon (310)206-6369 Recruiting 000817. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 000817. CONNECTICUT Connecticut Children's Med Ctr 263 Farmington Ave Farmington, CT 060303805 Gail Karas (860)679-2320 Recruiting 001031. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 Recruiting 000817. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Susan Zamer (202)884-2837 Recruiting 000817. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 000817. FLORIDA Sacred Heart Children's Hosp / CMS of Florida 5192 Bayou Blvd Pensacola, FL 32503 Michelle Zubon McAtee (850)484-5040 Recruiting 010316. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Brenda Haliburton-Jones (305)548-4445 Recruiting 000817. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 000817. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 000817. GEORGIA Med College of Georgia 1120 15th St / Dept of Pediatrics / HF 1135 Augusta, GA 30912 Teresa Horne (706)721-2437 Recruiting 010316. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 Recruiting 000817. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 000817. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 000817. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 Recruiting 000817. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 000817. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000817. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 000817. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 000817. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 000817. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 000817. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 Recruiting 000817. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 000817. NEW JERSEY UMDNJ - Robert Wood Johnson Med School / Pediatrics One Robert Wood Johnson Place New Brunswick, NJ 089030019 Silvia Callejas (732)235-7382 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 (973)972-3118 Recruiting 000817. NEW JERSEY Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl One Cooper Plaza Camden, NJ 08103 Mary Jo Hoyt (973)972-3118 Recruiting 000817. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 000817. NEW YORK SUNY - Brooklyn 450 Clarkson Ave / Box 49 Brooklyn, NY 11203 Denise Swindell (718)270-3185 No longer recruiting 010712. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000817. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 Recruiting 000817. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 000817. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000817. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 000817. NEW YORK Children's Hosp at Albany Med Ctr 47 New Scotland Ave / A-111 Albany, NY 12208 Mary Ellen Adams (518)262-6888 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 (516)444-1313 Recruiting 000817. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 000817. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 000817. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 000817. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 000817. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 000817. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 000817. PENNSYLVANIA Saint Christopher's Hosp for Children Erie Ave at Front St Philadelphia, PA 191341095 Audrey Kamrin (215)427-5284 Recruiting 000817. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 Recruiting 000817. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 000817. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 000817. VIRGINIA Children's Hosp of the King's Daughters 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 Recruiting 010118. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 Recruiting 000817. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (800)411-1222 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 (800)411-1222 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 (800)411-1222 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 (415)476-9554 Recruiting 990623. COLORADO Denver CPCRA / Denver Public Hlth 605 Bannock St Denver, CO 802044507 Jack Rouff (303)436-7184 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 (203)785-3557 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 (202)745-8301 No longer recruiting PEND 000111. GEORGIA AIDS Research Consortium of Atlanta 131 Ponce de Leon Ave / Suite 130 Atlanta, GA 303081962 Melanie Thompson MD (404)876-2317 No longer recruiting 010528. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd #108 Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting PEND 990513. LOUISIANA Louisiana Comm AIDS Rsch Prog / Tulane Univ Med 1430 Tulane Ave / TB 21 New Orleans, LA 70112 Janice Walker (504)584-1971 Recruiting PEND 990602. MICHIGAN Henry Ford Hosp 2799 West Grand Blvd / CFP-104 Detroit, MI 48202 Diane Mastro-Polak (313)876-2798 Recruiting 990513. MICHIGAN Wayne State Univ - WSU/DMC / Univ Hlth Ctr 4201 Saint Antoine / POD 7C Detroit, MI 48201 Jan Kosmyna (313)993-0923 Recruiting 990623. NEW JERSEY Southern New Jersey AIDS Clinical Trials Dept of Medicine / 3 Cooper Plaza / Suite 513 Camden, NJ 08103 Carol Graeber (856)963-6890 Recruiting PEND 990602. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Robert C Sawyer (973)483-3444 Recruiting PEND 990513. NEW MEXICO Partners in Research / New Mexico 915 Camino de Salud NE Albuquerque, NM 87131 Cynthia Nicholson (505)272-6501 Recruiting PEND 990602. NEW YORK Harlem AIDS Treatment Grp / Harlem Hosp Ctr 506 Lenox Ave / Rm 3101A New York, NY 10037 Luis Fuentes (212)939-2957 Recruiting 990623. OREGON The Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 Recruiting 990713. PENNSYLVANIA Philadelphia FIGHT 1233 Locust St / 5th Floor Philadelphia, PA 19107 Jane Shull (215)985-4448 Recruiting PEND 990510. TEXAS Univ TX Health Science Ctr 6431 Fannin St Houston, TX 77030 Hilda Cuervo (713)500-6751 Recruiting 001101. VIRGINIA Richmond AIDS Consortium / Div of Infect Diseases PO Box 980049 Richmond, VA 232980049 Vinnie Mitchell (757)828-2477 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 (415)554-9065 Recruiting 990413. COLORADO Denver Dept of Public Health / HIVNET 605 Bannock St / Room 220 Denver, CO 80204 Ken Miller (303)436-7266 Recruiting 990413. ILLINOIS Howard Brown Health Ctr 4025 North Sheridan Rd Chicago, IL 60613 David McKirnan (312)413-2634 Recruiting 990413. MASSACHUSETTS Fenway Community Health Ctr 7 Haviland St Boston, MA 02115 Dr Ken Mayer (401)729-2776 Recruiting 990413. NEW YORK New York Blood Ctr Project ACHIEVE / 1309 Fulton Ave Room 312 Bronx, NY 10456 Cladd Stevens (212)388-0008 Recruiting 990413. WASHINGTON Univ of Washington 901 Boren Ave Suite 1300 UW Box 3599227 Seattle, WA 98104 Dennis Torres (206)521-5812 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 (800)411-1222 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 (800)411-1222 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 (205)558-2328 No longer recruiting 010222. ALABAMA Univ of South Alabama 1504 Springhill Avenue Mobile, AL 36604 Julie Bebawy (334)405-5107 Recruiting 990802. ARIZONA Phoenix Childrens Hosp 909 East Brill Street Phoenix, AZ 85006 Laura Clarke-Steffan (602)239-5261 Recruiting 010621. CALIFORNIA Children's Hosp of Los Angeles/UCLA Med Ctr 4650 Sunset Blvd Los Angeles, CA 900276016 Zane O'Keefe (310)206-6369 Recruiting 990917. CALIFORNIA Harbor - UCLA Med Ctr / UCLA School of Medicine 1000 West Carson Blvd Los Angeles, CA 905022004 Zane O'Keefe (310)206-6369 Recruiting 990917. CALIFORNIA UCSD Med Ctr / Pediatrics / Clinical Sciences 9500 Gilman Dr La Jolla, CA 920930672 Candace McIvor (619)534-7170 Recruiting 990330. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 990719. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 990414. CONNECTICUT Connecticut Children's Med Ctr 263 Farmington Ave Farmington, CT 060303805 Gail Karas (860)679-2320 Recruiting 000404. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 990623. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 990329. FLORIDA Univ of Florida Gainesville 1600 Archer Rd / SW Gainesville, FL 32610 Carol Delany (352)846-3598 Recruiting 000726. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 990623. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 990917. FLORIDA Palm Beach County Health Dept 301 Broadway Riviera Beach, FL 33404 Patricia Vann (561)882-3111 Recruiting 990917. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 Recruiting 990402. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 990707. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 990917. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 No longer recruiting 010130. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 990706. LOUISIANA Earl K Long Early Intervention Clinic 1430 Tulane Ave TB-8 New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 990917. MASSACHUSETTS Children's Hosp of Boston 300 Longwood Ave / Carnegie Building Boston, MA 021155724 Robert Holt (617)355-8198 Recruiting 990408. MASSACHUSETTS Boston City Hosp / Pediatrics 774 Albany St / Finland Lab / Room 301 Boston, MA 02118 Anne Marie Regan (617)414-5813 Recruiting 990917. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 990407. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 No longer recruiting 001110. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 990405. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 Recruiting 990730. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 990917. NEW YORK SUNY - Brooklyn 450 Clarkson Ave / Box 49 Brooklyn, NY 11203 Denise Swindell (718)270-3185 No longer recruiting 010307. NEW YORK Incarnation Children's Ctr / Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 990615. NEW YORK North Shore Univ Hosp 865 Northern Boulevard / Suite 104 Great Neck, NY 11021 Lourdes Rodriguez (516)622-5085 Recruiting 990719. NEW YORK Bellevue Hosp / New York Univ Med Ctr 550 First Ave New York, NY 10016 Nagamah Deygoo (212)263-6426 Recruiting 001121. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 990615. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 990917. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 Recruiting 010318. NEW YORK Montefiore Med Ctr Adolescent AIDS Program 111 East 210th St Bronx, NY 10467 Dina Monte (718)882-0023 Recruiting 990917. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 990809. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 990512. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 990412. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 No longer recruiting 010507. PENNSYLVANIA Children's Hosp of Philadelphia 34th St & Civic Ctr Blvd Philadelphia, PA 191044318 Carol Vincent (215)590-2262 Recruiting 990412. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 990202. TEXAS Texas Children's Hosp / Baylor Univ 6621 Fannin St / MC1-3291 Houston, TX 77030 Kathryn Owl (832)824-2583 Recruiting 991004. TEXAS Children's Med Ctr of Dallas 1935 Motor St Dallas, TX 75235 Diane Ramirez (214)640-6198 Recruiting 990706. VIRGINIA Children's Hosp of the King's Daughters 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 Recruiting 990716. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (415)476-9554 Recruiting 990408. COLORADO Denver CPCRA / Denver Public Hlth 605 Bannock St Denver, CO 802044507 Jack Rouff (303)436-7184 Recruiting 990616. CONNECTICUT Yale Univ School of Medicine / AIDS Program 135 College St / Suite 323 New Haven, CT 06510 Laurie Andrews (203)785-3557 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 (202)745-8301 Recruiting 990129. GEORGIA AIDS Research Consortium of Atlanta 131 Ponce de Leon Ave / Suite 130 Atlanta, GA 303081962 Melanie Thompson MD (404)876-2317 No longer recruiting 010528. ILLINOIS AIDS Research Alliance - Chicago 2800 North Sheridan Rd #108 Chicago, IL 60657 Rita Verheggen (773)244-5802 Recruiting 990121. LOUISIANA Louisiana Comm AIDS Rsch Prog / Tulane Univ Med 1430 Tulane Ave / TB 21 New Orleans, LA 70112 Janice Walker (504)584-1971 Recruiting 990616. MICHIGAN Henry Ford Hosp 2799 West Grand Blvd / CFP-104 Detroit, MI 48202 Diane Mastro-Polak (313)876-2798 Recruiting 990202. MICHIGAN Wayne State Univ - WSU/DMC / Univ Hlth Ctr 4201 Saint Antoine / POD 7C Detroit, MI 48201 Jan Kosmyna (313)993-0923 Recruiting 990121. NEW JERSEY Southern New Jersey AIDS Cln Trials / Dept of Med 3 Cooper Plaza / Suite 220 Camden, NJ 08103 Maryann LiVolsi (609)963-6890 Recruiting 990616. NEW JERSEY North Jersey Community Research Initiative 393 Central Ave / Suite 301 Newark, NJ 071032842 Robert C Sawyer (973)483-3444 Recruiting 990204. NEW MEXICO Partners in Research / New Mexico 915 Camino de Salud NE Albuquerque, NM 87131 Cynthia Nicholson (505)272-6501 Recruiting 990616. NEW YORK Harlem AIDS Treatment Grp / Harlem Hosp Ctr 506 Lenox Ave / Rm 3101A New York, NY 10037 Luis Fuentes (212)939-2957 Recruiting 990218. OREGON The Research and Education Group 2701 NW Vaughn St Portland, OR 97210 Norma Martinez (503)229-8428 Recruiting 990616. PENNSYLVANIA Philadelphia FIGHT 1233 Locust St / 5th Floor Philadelphia, PA 19107 Jane Shull (215)985-4448 Recruiting 990325. TEXAS Univ TX Health Science Ctr 6431 Fannin St Houston, TX 77030 Hilda Cuervo (713)500-6751 Recruiting 010118. VIRGINIA Richmond AIDS Consortium / Div of Infect Diseases PO Box 980049 Richmond, VA 232980049 Vinnie Mitchell (757)828-2477 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 (800)411-1222 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 (323)226-2342 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 (303)372-5535 Recruiting 000926. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 000926. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 000926. FLORIDA Univ of Miami / Jackson Memorial Hosp 1500 Northwest 12th Ave / 8th Floor Miami, FL 33136 Patricia Bryan (305)243-2154 Recruiting 000926. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 No longer recruiting 010528. LOUISIANA Univ Hosp 2021 Perdido St New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 000926. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 000926. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 Recruiting 000926. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 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 (973)972-3118 Recruiting 000926. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 000926. OTHER Univ of Puerto Rico / Univ Children's Hosp AIDS GPO Box 365067 San Juan, PR 009365067 Carmen Rivera (787)759-9595 Recruiting 000926. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 Recruiting 000926. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (205)558-2328 Recruiting 990917. ALABAMA Univ of South Alabama 1504 Springhill Avenue Mobile, AL 36604 Julie Bebawy (334)405-5107 Recruiting 000801. ARIZONA Phoenix Childrens Hosp 909 East Brill Street Phoenix, AZ 85006 Judith O'Haver (602)239-5263 Recruiting 990917. CALIFORNIA Harbor - UCLA Med Ctr / UCLA School of Medicine 1000 West Carson Blvd Los Angeles, CA 905022004 Zane O'Keefe (310)206-6369 Recruiting 981217. CALIFORNIA UCSF / Moffitt Hosp - Pediatric 505 Parnassus Ave San Francisco, CA 941430105 Debbie Trevithick (415)476-6480 Recruiting 981022. CALIFORNIA San Francisco Gen Hosp 1001 Potrero Ave / Ward 6 / D-4 San Francisco, CA 94110 Kelly Slaven (415)206-8919 Recruiting 981022. CALIFORNIA Los Angeles County - USC Med Ctr 1929 Zonal Ave / Health Science Campus (CAB-HSC) Los Angeles, CA 90033 Andrea Kovacs (323)226-5068 Recruiting 981123. CALIFORNIA Long Beach Mem UCLA School of Med / 10833 Le Conte Ave Los Angeles, CA 900951752 Zane O'Keefe (310)206-6369 Recruiting 991015. CALIFORNIA UCLA Med Ctr / Pediatric 10833 Le Conte Ave Los Angeles, CA 900951752 Zane OKeefe (310)206-6369 Recruiting 990601. COLORADO Children's Hosp of Denver 1056 East 19th Ave / B-055 Denver, CO 802181088 Carol Salbenblatt (303)861-6751 Recruiting 990917. CONNECTICUT Univ of Connecticut / Farmington 263 Farmington Ave Farmington, CT 06032 Gail Karas (860)679-2320 Recruiting 990113. CONNECTICUT Connecticut Children's Med Ctr 263 Farmington Ave Farmington, CT 060303805 Gail Karas (860)679-2320 Recruiting 990917. CONNECTICUT Yale Univ Med School 20 York St / Pediatric AIDS Care Program New Haven, CT 06504 Donna Schroeder (203)688-6093 Recruiting 980917. DISTRICT OF COLUMBIA Children's Hosp of Washington DC 111 Michigan Ave NW Washington, DC 200102916 Julie Ziegler (202)884-4708 Recruiting 001110. DISTRICT OF COLUMBIA Washington Hosp Ctr 110 Irving St NW Washington, DC 200102931 Rene Smit (202)877-5811 Recruiting 001019. DISTRICT OF COLUMBIA Howard Univ Hosp 2041 Georgia Ave NW Washington, DC 20060 Helga Finke (202)865-1248 Recruiting 981210. FLORIDA Univ of Miami (Pediatric) Jackson Memorial Hospital / 1400 NW 10th Avenue Miami, FL 33161 Charlotte Goldberg (305)243-4447 Recruiting 980928. FLORIDA Univ of Miami / Jackson Memorial Hosp 1500 Northwest 12th Ave / 8th Floor Miami, FL 33136 Patricia Bryan (305)243-2154 Recruiting 980928. FLORIDA North Broward Hosp District 417 South Andrews Ave Fort Lauderdale, FL 33311 Pamela Munger (954)728-8080 Recruiting 990917. FLORIDA Univ of Florida Health Science Ctr / Pediatrics 653-1 West 8th St Jacksonville, FL 32209 Michelle Eagle (904)549-5331 Recruiting 990917. GEORGIA The Med Ctr Inc 710 Center St Columbus, GA 31901 Dawn Barnes (706)571-1449 Recruiting 990917. GEORGIA Med College of Georgia 1120 15th St / Dept of Pediatrics / HF 1135 Augusta, GA 30912 Teresa Horne (706)721-2437 Recruiting 990917. GEORGIA Emory Univ Hosp / Pediatrics 341 Ponce de Leon Ave Atlanta, GA 30306 Renata Dennis (404)616-6240 Recruiting 981119. ILLINOIS Chicago Children's Memorial Hosp 2300 Children's Plaza / PO Box 155 Chicago, IL 606143394 Debbie Fonken-Cloutier (773)880-3669 Recruiting 990723. ILLINOIS Univ of Chicago Children's Hosp 5841 South Maryland Ave / MC 6054 Chicago, IL 606371470 Pamela Lofton (773)702-4853 Recruiting 981105. ILLINOIS Univ of Illinois College of Medicine / Pediatrics 840 South Wood St Chicago, IL 60612 Julia Camacho (312)413-8089 Recruiting 990917. ILLINOIS Cook County Hosp 2020 West Harrison St Chicago, IL 60612 Cynthia Booth (312)572-4547 Recruiting 991022. LOUISIANA Univ Hosp 2021 Perdido St New Orleans, LA 70112 Kim Anglin (504)586-3804 Recruiting 990218. LOUISIANA Tulane Univ / Charity Hosp of New Orleans 1430 Tulane Ave / Pediatric AIDS Clinical Trials Unit New Orleans, LA 701122699 Kim Anglin (504)586-3804 Recruiting 981009. MASSACHUSETTS Brigham and Women's Hosp 75 Francis St / Children's Hosp AIDS Program Boston, MA 02115 Arlene Buck (617)732-5452 Recruiting 981215. MASSACHUSETTS Univ of Massachusetts Med School 55 Lake Ave North Worcester, MA 016550001 Donna Christian (508)856-1692 Recruiting 980923. MASSACHUSETTS Baystate Med Ctr of Springfield 759 Chestnut St / SHU-Main 3 Springfield, MA 01199 MariPat Toye (413)794-5399 Recruiting 981022. MARYLAND Johns Hopkins Hosp - Pediatric 600 North Wolfe St / Park 2-257 Baltimore, MD 212874933 Suzanne Marvin (410)955-9749 Recruiting 010723. MICHIGAN Children's Hosp of Michigan 3901 Beaubien Blvd Detroit, MI 48201 Charnell Cromer (313)745-4450 Recruiting 981204. MISSOURI Washington Univ School of Medicine One Childrens Place St Louis, MO 63110 Phyllis Ballard (314)454-4145 Recruiting 000317. MISSISSIPPI Univ of Mississippi Med Ctr 350 West Woodrow Wilson Jackson, MS 39213 Sondra Sadler (601)984-6688 Recruiting 981119. NORTH CAROLINA Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr PO Box 3499 Durham, NC 27710 John Swetnam (919)684-6335 Recruiting 990330. NORTH CAROLINA Duke Univ Med Ctr PO Box 3499 Durham, NC 277103499 John Swetnam (919)684-6335 Recruiting 980923. NEW JERSEY St Peter's Med Ctr 254 Easton Ave New Brunswick, NJ 08903 Marian Lake (732)745-8600 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 (973)972-3118 Recruiting 990119. NEW YORK Harlem Hosp Ctr 506 Lenox Ave / Room 16-119 New York, NY 10037 Delia Calo (212)939-4045 Recruiting 000419. NEW YORK Metropolitan Hosp Ctr 1901 First Ave / Room 523 New York, NY 10029 Karen Novita (212)423-7103 Recruiting 990402. NEW YORK Columbia Presbyterian Med Ctr 622 West 168th St New York, NY 10032 Marie Donahue (212)305-7222 Recruiting 981119. NEW YORK Bronx Lebanon Hosp Ctr 1650 Selwyn Ave / Milstein Building / Room 2C Bronx, NY 10457 Wanda Biernick (718)918-4602 Recruiting 981001. NEW YORK Children's Hosp at Albany Med Ctr 47 New Scotland Ave / A-111 Albany, NY 12208 Mary Ellen Adams (518)262-6888 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 (516)444-1313 Recruiting 981224. NEW YORK Bronx Municipal Hosp Ctr/Jacobi Med Ctr 1400 Pelham Parkway South Bronx, NY 10461 Wanda Biernick (718)918-4516 Recruiting 001013. NEW YORK Univ of Rochester Med Ctr 601 Elmwood Ave / Box 690 Rochester, NY 146420001 Barbra Murante (716)275-1549 Recruiting 990224. NEW YORK Schneider Children's Hosp 269-01 76th Ave / Room 235 New Hyde Park, NY 11040 Connie Colter (718)470-3300 No longer recruiting 001110. NEW YORK SUNY Health Sciences Ctr at Syracuse / Pediatrics 750 East Adams St Syracuse, NY 13210 Kathie Contello (315)464-6331 Recruiting 990917. OHIO Columbus Children's Hosp 700 Children's Dr Columbus, OH 432052696 Jane Hunkler (614)722-4460 Recruiting 990809. OTHER San Juan City Hosp Centro Medico / Mail Station 128 / GPO Box 70344 San Juan, PR 009367344 Moraima Rivera (809)764-3083 Recruiting 990916. OTHER Ramon Ruiz Arnau Univ Hosp / Pediatrics Laurel Ave Bayamon, PR 00956 Eva Reyes (787)798-2733 Recruiting 981207. PENNSYLVANIA Temple Univ School of Medicine Erie Ave at Front St Philadelphia, PA 191341095 Harold Lischner (215)427-5284 Recruiting 001205. PENNSYLVANIA Thomas Jefferson Univ Hosp Jefferson Medical College Dept of OB/GYN / 834 Chestnut St Philadelphia, PA 191075098 Mary Talucci (215)955-9243 Recruiting 010214. SOUTH CAROLINA Med Univ of South Carolina 171 Ashley Ave / 312 Clinical Science Building Charleston, SC 294253312 Barbara Stovall (803)792-5311 Recruiting 980917. TENNESSEE Methodist Hosp Central 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-3485 Recruiting 990917. TENNESSEE Regional Med Ctr at Memphis 877 Jefferson Ave / Room Ed15 Memphis, TN 38103 Micki Roy (901)495-3485 Recruiting 990917. TENNESSEE Saint Jude Children's Research Hosp of Memphis 332 North Lauderdale Memphis, TN 381052794 Micki Roy (901)495-2004 Recruiting 980923. TENNESSEE Vanderbilt Univ Med Ctr 1161 21st Ave South / MCN D-7235 Nashville, TN 372322581 Peggy Bender (615)322-2250 Recruiting 000310. TEXAS Children's Med Ctr of Dallas 1935 Motor St Dallas, TX 75235 Diane Ramirez (214)640-6198 Recruiting 990707. VIRGINIA Children's Hosp of the King's Daughters 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 Recruiting 001031. VIRGINIA Med College of Virginia Division of Infectious Diseases / 1001 E Broad St Suite LL25 Richmond, VA 23219 Tima Smith (804)828-3436 Recruiting 990917. VIRGINIA Senetara Norfolk Gen Hosp 601 Children's Lane Norfolk, VA 23507 Donna Sandifer (757)668-7238 Recruiting 001031. WASHINGTON Children's Hospital & Medical Center / Seattle ACTU 4800 Sand Point Way NE Seattle, WA 981050371 Kathleen Mohan (206)528-5020 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 (800)411-1222 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 (800)411-1222 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 (800)411-1222 Recruiting USA accrual 000620. SS 2 /C?