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Previous Volume 333:1534-1540 December 7, 1995 Number 23 Next

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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 -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.

Source Information

From the Aaron Diamond AIDS Research Center, New York University School of Medicine, New York (M.M., A.M.H., D.D.H.); the University of Alabama at Birmingham, Birmingham (M.S.); Washington University, St. Louis (W.G.P.); the Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Ill. (A.H., J.M.V., D.H., J.M.L.); Los Angeles County–University of Southern California Medical Center, Los Angeles (F.S.); and Therafirst Medical Center, Fort Lauderdale, Fla. (A.L.M.).

Address reprint requests to Dr. Ho at the Aaron Diamond AIDS Research Center, 455 First Ave., New York, NY 10016.

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