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NLM AIDSLINE
Prolongation of life and prevention of AIDS in advanced HIV immunodeficiency with ritonavir.
Cameron B; Heath-Chiozzi M; Kravcik S; Mills R; Potthoff A; Henry D;
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:162. Unique

Ritonavir is a potent, orally bioavailable HIV protease inhibitor. We designed and conducted an international multi-centre randomized placebo-controlled clinical trial of ritonavir 600 mg twice daily for outcomes of death and new AIDS-defining illnesses or selected recurrences (pneumocystis pneumonia, esophageal candidiasis, and chronic herpetic ulcer). Concurrent anti-HIV therapy was permitted. Crossover to open ritonavir for any AIDS outcome was provided after four months on study. 1090 HIV patients with CD4 T lymphocyte count under 101 cells/mm3and over nine months prior anti-HIV therapy were randomized in 67 North American, European and Australian centres, from April to July 1995. Preliminary unblinded analysis was conducted in December after 191 first outcomes occurred after one month on study. Baseline characteristics did not differ, with median CD4 T cells 18/mm3 (mean 30, standard deviation 28) in ritonavir and 22/mm3 (m35, SD28) in placebo soups. Drug discontinuation associated with adverse events occurred in 91 (17%) of 543 ritonavir, versus 32 (6%) of 547 placebo patients. Events included nausea, vomiting, weakness and diarrhea mostly beginning during the first two weeks on study. In median 6.1 range (0.2 to 7.7) months follow-up, 26 (4.8%) ritonavir versus 46 (8.4%) placebo patients died (p=0.02, hazard ratio 0.57, 95% CI 0.35 - 0.92). For outcomes after one month on study, AIDS-or-death occurred in 69 (12.7%) versus 149 (27.3%, p less than 0.001, HR 0.44, 95%CI 0.33 - 0.58). This one year study in advanced HIV immunodeficiency demonstrates that ritonavir therapy prevents AIDS complications and prolongs life.

AIDS-Related Opportunistic Infections/PREVENTION & CONTROL Acquired Immunodeficiency Syndrome/*PREVENTION & CONTROL CD4 Lymphocyte Count HIV Infections/*DRUG THERAPY/PHYSIOPATHOLOGY HIV Protease Inhibitors/*THERAPEUTIC USE Human *Life Expectancy Placebos Thiazoles/*THERAPEUTIC USE Treatment Outcome Valine/*THERAPEUTIC USE ABSTRACT

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