Document 0647
 DOCN  M9480647
 TI    Zidovudine twice daily in asymptomatic subjects with HIV infection and a
       high risk of progression to AIDS: a randomized, double-blind
       placebo-controlled study. The European-Australian Collaborative Group
       (Study 017).
 DT    9410
 AU    Mulder JW; Cooper DA; Mathiesen L; Sandstrom E; Clumeck N; Gatell JM;
       French M; Donovan B; Gray F; Yeo JM; et al; Slotervaatziekenhuis,
       Department of Internal Medicine, Amsterdam,; The Netherlands.
 SO    AIDS. 1994 Mar;8(3):313-21. Unique Identifier : AIDSLINE MED/94304551
 AB    OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in
       subjects with asymptomatic HIV-1 infection and a high risk of
       progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled
       trial. SETTING: Multicentre study in five European countries and
       Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell
       counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects
       with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were
       randomly assigned to receive zidovudine 500 mg or placebo twice daily
       for 104 weeks, following a 250 mg four times daily dose regimen for the
       first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the
       development of AIDS or severe AIDS-related complex (ARC). Before
       unblinding the study other end-points were defined: the development of
       Centers for Disease Control and Prevention (CDC) group IV disease (AIDS,
       severe ARC and other CDC stage IV disease) and the development of
       symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease
       and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia
       and toxicity were also reviewed. RESULTS: Median treatment duration was
       57 weeks for the placebo and 60 weeks for the zidovudine group,
       respectively. Progression to AIDS or severe ARC occurred in 17 placebo
       and 12 zidovudine recipients (log-rank P = 0.26). However, in the first
       of the 2 study years the rate of progression to AIDS or severe ARC was
       significantly higher in the placebo than in the zidovudine group.
       Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a
       trend in a delay in progression to CDC stage IV disease was observed (P
       = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above
       baseline levels for longer than placebo recipients (P = 0.04). HIV
       p24-antigen levels decreased in the zidovudine group and returned to
       pretreatment levels by week 36. Substantial toxicity was not observed.
       CONCLUSIONS: Zidovudine twice daily is effective in delaying progression
       to symptomatic HIV disease in high-risk, asymptomatic HIV-infected
       subjects. Modified definitions of clinical end-points may be useful for
       evaluating Phase III trials in comparable patient groups in the light of
       changes in the definition of AIDS and the increasing use of primary
       prophylaxis against opportunistic infections.
 DE    Acquired Immunodeficiency Syndrome/PREVENTION & CONTROL  AIDS-Related
       Complex/PREVENTION & CONTROL  Double-Blind Method  Europe  Female  Human
       HIV Core Protein p24/BLOOD  HIV Infections/BLOOD/*DRUG
       THERAPY/MICROBIOLOGY  *HIV-1  Leukocyte Count  Male  Patient Compliance
       Risk Factors  Safety  Time Factors  T4 Lymphocytes
       Zidovudine/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS  CLINICAL TRIAL
       JOURNAL ARTICLE  MULTICENTER STUDY  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).