       Document 0284
 DOCN  M9620284
 TI    A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to
       treat HIV-1 infection.
 DT    9602
 AU    Markowitz M; Saag M; Powderly WG; Hurley AM; Hsu A; Valdes JM; Henry D;
       Sattler F; La Marca A; Leonard JM; et al; Aaron Diamond AIDS Research
       Center, New York University School of; Medicine, New York 10016, USA.
 SO    N Engl J Med. 1995 Dec 7;333(23):1534-9. Unique Identifier : AIDSLINE
       MED/96067436
 AB    BACKGROUND. Ritonavir is a potent inhibitor in vitro of human
       immunodeficiency virus type 1 (HIV-1) protease, which is needed for
       virions to mature and become infective. We assessed the safety and
       efficacy of ritonavir in patients with HIV-1 infection. METHODS. We
       administered ritonavir orally to 62 patients in one of four dosages
       during a 12-week trial containing a 4-week randomized,
       placebo-controlled, double-blinded phase followed by an 8-week
       dose-blinded phase. We assessed the response with serial measurements of
       plasma viremia and serial CD4 cell counts. RESULTS. Fifty-two patients
       completed the 12-week trial. Diarrhea and nausea were the most common
       side effects, and reversible elevations in serum triglyceride and
       gamma-glutamyltransferase levels were the most frequent laboratory
       abnormalities. Ritonavir had a rapid antiviral effect, with a mean
       maximal reduction in the number of copies of HIV-1 RNA per milliliter of
       plasma that ranged from 0.86 to 1.18 log in the four dosage groups.
       After 12 weeks of treatment, the antiviral effect was partially
       maintained, with a mean reduction in plasma viremia of 0.5 log. When we
       used a more sensitive assay for HIV-1 RNA in a subgroup of 20 patients,
       we found that plasma viremia decreased by a mean of 1.7 log. This
       antiviral effect was partly sustained at week 12, with a mean reduction
       of approximately 1.1 log. The patients' CD4 cell counts rose during
       treatment with ritonavir (median increase, 74 and 83 cells per cubic
       millimeter at weeks 4 and 12, respectively). CONCLUSIONS. The protease
       inhibitor ritonavir is well tolerated and has a potent antiviral effect,
       as shown by substantial decreases in plasma viremia and significant
       elevations in CD4 cell counts. Expanded clinical trials of ritonavir are
       warranted.
 DE    Adult  Antiviral Agents/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC
       USE  CD4 Lymphocyte Count/DRUG EFFECTS  Double-Blind Method  Female
       Human  HIV Infections/*DRUG THERAPY/IMMUNOLOGY  HIV Protease
       Inhibitors/ADVERSE EFFECTS/PHARMACOKINETICS/  *THERAPEUTIC USE
       HIV-1/*DRUG EFFECTS  Male  RNA, Viral/BLOOD  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  Thiazoles/*THERAPEUTIC USE  Treatment
       Outcome  Valine/*ANALOGS & DERIVATIVES/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).

