       Document 0773
 DOCN  M95A0773
 TI    A comparison of immediate with deferred zidovudine therapy for
       asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per
       cubic millimeter. AIDS Clinical Trials Group [see comments]
 DT    9510
 AU    Volberding PA; Lagakos SW; Grimes JM; Stein DS; Rooney J; Meng TC;
       Fischl MA; Collier AC; Phair JP; Hirsch MS; et al; University of
       California, San Francisco, USA.
 SO    N Engl J Med. 1995 Aug 17;333(7):401-7. Unique Identifier : AIDSLINE
       MED/95342190
 CM    Comment in: N Engl J Med 1995 Aug 17;333(7):450-1
 AB    BACKGROUND. The clinical benefits of zidovudine remain unproved in
       patients with asymptomatic human immunodeficiency virus (HIV) infection
       when CD4 cell counts exceed 500 per cubic millimeter. We compared
       zidovudine therapy given immediately with deferred therapy in such
       subjects. METHODS. Beginning in 1987, subjects with asymptomatic HIV
       infection and 500 or more CD4 cells per cubic millimeter were randomly
       assigned to receive placebo or zidovudine (either 500 or 1500 mg per
       day, starting immediately). In 1989, the study was modified so that
       open-label treatment with 500 mg of zidovudine per day (deferred
       therapy) was offered when CD4 cell counts fell below 500 per cubic
       millimeter. The study end points included overall survival, survival
       free of the acquired immunodeficiency syndrome (AIDS), toxic effects,
       and changes in CD4 cell counts. RESULTS. There were 1637 subjects who
       could be evaluated: 547 in the deferred-therapy group, 549 in the group
       receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg
       group. The subjects were followed for up to 6.5 years (group medians,
       4.8, 4.8, and 4.9, respectively). There was no significant difference in
       AIDS-free survival in the deferred-therapy group as compared with the
       low-dose or high-dose groups (81 cases of progression to AIDS or death
       vs. 81 and 74, respectively; P = 0.95 and P = 0.13) or in overall
       survival (51 deaths vs. 47 and 46; P = 0.25 and P = 0.16). The decline
       in CD4 cells was slower in both immediate-therapy groups than in the
       deferred-therapy group (P < 0.001 for both). Adverse effects were
       uncommon, and before the study modification their incidence was similar
       among the treatment groups, but severe anemia and granulocytopenia were
       more frequent in the 1500-mg group than in the deferred-therapy group (P
       < 0.001). CONCLUSIONS. In asymptomatic, HIV-infected adults with 500 or
       more CD4 cells per cubic millimeter, treatment with zidovudine slows the
       decline in the CD4 cell count but does not significantly prolong either
       AIDS-free or overall survival. These results do not encourage the
       routine use of zidovudine monotherapy in this population.
 DE    Acquired Immunodeficiency Syndrome/*PREVENTION & CONTROL  Adult
       Comparative Study  CD4 Lymphocyte Count/DRUG EFFECTS  Disease
       Progression  Disease-Free Survival  Double-Blind Method  Follow-Up
       Studies  Human  HIV Infections/*DRUG THERAPY/IMMUNOLOGY/MORTALITY  Male
       Proportional Hazards Models  Support, U.S. Gov't, P.H.S.  Survival
       Analysis  Time Factors  Zidovudine/ADMINISTRATION & DOSAGE/ADVERSE
       EFFECTS/*THERAPEUTIC  USE  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).

