A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.

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:

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.

• 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.)

Chemical References

• Antiviral Agents
• HIV Protease Inhibitors
• RNA, Viral
• Thiazoles
• Valine
• Ritonavir

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)