       Document 0283
 DOCN  M9620283
 TI    Treatment with lamivudine, zidovudine, or both in HIV-positive patients
       with 200 to 500 CD4+ cells per cubic millimeter. North American HIV
       Working Party [see comments]
 DT    9602
 AU    Eron JJ; Benoit SL; Jemsek J; MacArthur RD; Santana J; Quinn JB;
       Kuritzkes DR; Fallon MA; Rubin M; University of North Carolina at Chapel
       Hill 27599-7030, USA.
 SO    N Engl J Med. 1995 Dec 21;333(25):1662-9. Unique Identifier : AIDSLINE
       MED/96083638
 CM    Comment in: N Engl J Med 1995 Dec 21;333(25):1704-5
 AB    BACKGROUND. The reverse-transcriptase inhibitor lamivudine has in vitro
       synergy with zidovudine against the human immunodeficiency virus (HIV).
       We studied the activity and safety of lamivudine plus zidovudine as
       compared with either drug alone as treatment for patients with HIV
       infection, most of whom had not previously received zidovudine. METHODS.
       Three hundred sixty-six patients with 200 to 500 CD4+ cells per cubic
       millimeter who had received zidovudine for four weeks or less were
       randomly assigned to treatment with one of four regimens: 300 mg of
       lamivudine every 12 hours; 200 mg of zidovudine every 8 hours; 150 mg of
       lamivudine every 12 hours plus zidovudine; or 300 mg of lamivudine every
       12 hours plus zidovudine. The study was double-blind and lasted 24
       weeks, with an extension phase for another 28 weeks. RESULTS. Over the
       24-week period, the low-dose and high-dose regimens combining lamivudine
       and zidovudine were associated with greater increases in the CD4+ cell
       count (P = 0.002 and P = 0.015, respectively) and the percentage of CD4+
       cells (P < 0.001 for both) and with greater decreases in plasma levels
       of HIV-1 RNA (P < 0.001 for both) than was treatment with zidovudine
       alone. Combination therapy was also more effective than lamivudine alone
       in lowering plasma HIV-1 RNA levels and increasing the percentage of
       CD4+ cells (P < 0.001 for all comparisons), and these advantages
       persisted through 52 weeks. Adverse events were no more frequent with
       combination therapy than with zidovudine alone. CONCLUSIONS. In
       HIV-infected patients with little or no prior antiretroviral therapy,
       treatment with a combination of lamivudine and zidovudine is well
       tolerated over a one-year period and produces more improvement in
       immunologic and virologic measures than does treatment with either agent
       alone.
 DE    Adult  Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC USE  Comparative
       Study  CD4 Lymphocyte Count/DRUG EFFECTS  Double-Blind Method  Drug
       Therapy, Combination  Female  Human  HIV Infections/*DRUG
       THERAPY/IMMUNOLOGY  *HIV-1/GENETICS  Male  Reverse Transcriptase
       Inhibitors/ADVERSE EFFECTS/*THERAPEUTIC USE  RNA, Viral/BLOOD  Support,
       Non-U.S. Gov't  Treatment Outcome  Zalcitabine/*ANALOGS &
       DERIVATIVES/ADVERSE EFFECTS/THERAPEUTIC  USE  Zidovudine/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).

