Abstract | 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:
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Authors | M Markowitz, M Saag, W G Powderly, A M Hurley, A Hsu, J M Valdes, D Henry, F Sattler, A La Marca, J M Leonard |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 333
Issue 23
Pg. 1534-9
(Dec 07 1995)
ISSN: 0028-4793 [Print] United States |
PMID | 7477168
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antiviral Agents
- HIV Protease Inhibitors
- RNA, Viral
- Thiazoles
- Valine
- Ritonavir
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Topics |
- Adult
- Antiviral Agents
(adverse effects, pharmacokinetics, therapeutic use)
- CD4 Lymphocyte Count
(drug effects)
- Double-Blind Method
- Female
- HIV Infections
(drug therapy, immunology)
- HIV Protease Inhibitors
(adverse effects, pharmacokinetics, therapeutic use)
- HIV-1
(drug effects)
- Humans
- Male
- RNA, Viral
(blood)
- Ritonavir
- Thiazoles
(therapeutic use)
- Treatment Outcome
- Valine
(analogs & derivatives, therapeutic use)
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