       Document 0285
 DOCN  M9620285
 TI    A short-term study of the safety, pharmacokinetics, and efficacy of
       ritonavir, an inhibitor of HIV-1 protease. European-Australian
       Collaborative Ritonavir Study Group.
 DT    9602
 AU    Danner SA; Carr A; Leonard JM; Lehman LM; Gudiol F; Gonzales J; Raventos
       A; Rubio R; Bouza E; Pintado V; et al; Academic Medical Center,
       Amsterdam, The Netherlands.
 SO    N Engl J Med. 1995 Dec 7;333(23):1528-33. Unique Identifier : AIDSLINE
       MED/96067435
 AB    BACKGROUND. Reverse-transcriptase inhibitors have only moderate clinical
       efficacy against the human immunodeficiency virus type 1 (HIV-1).
       Ritonavir is an inhibitor of HIV-1 protease with potent in vitro
       anti-HIV properties and good oral bioavailability. METHODS. We evaluated
       the antiviral activity and safety of ritonavir in a double-blind,
       randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive
       patients with 50 or more CD4+ lymphocytes per cubic millimeter. The
       patients were randomly assigned to one of four regimens of ritonavir
       therapy, or to placebo for four weeks and then (by random assignment) to
       one of the ritonavir regimens. RESULTS. During the first 4 weeks,
       increases in CD4+ lymphocyte counts and reductions in the log number of
       copies of HIV-1 RNA per milliliter of plasma were similar among the four
       dosage groups, but in the three lower-dosage groups there was a return
       to base-line levels by 16 weeks. After 32 weeks, in the seven patients
       in the highest-dosage group (600 mg of ritonavir every 12 hours), the
       median increase from base line in the CD4+ lymphocyte count was 230
       cells per cubic millimeter, and the mean decrease in the plasma
       concentration of HIV-1 RNA (as measured by a branched-DNA assay) was
       0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup
       of 17 patients in the two higher-dosage groups, RNA was also measured
       with an assay based on the polymerase chain reaction, and after eight
       weeks of treatment there was a mean maximal decrease in viral RNA of
       1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events
       included nausea, circumoral paresthesia, elevated hepatic
       aminotransferase levels, and elevated triglyceride levels. Ten
       withdrawals from the study were judged to be related to ritonavir
       treatment. CONCLUSIONS. In this short-term study, ritonavir was well
       tolerated and had potent activity against HIV-1, but its clinical
       benefits remain to be established.
 DE    Adult  Antiviral Agents/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC
       USE  CD4 Lymphocyte Count/DRUG EFFECTS  Double-Blind Method  Female
       Human  HIV Core Protein p24/BLOOD  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  Thiazoles/ADVERSE
       EFFECTS/PHARMACOKINETICS/*THERAPEUTIC USE  Treatment Outcome
       Valine/*ANALOGS & DERIVATIVES/ADVERSE EFFECTS/PHARMACOKINETICS/
       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).

