Regimens Using Two Protease Inhibitors Show Promise

CHICAGO--A new recipe for the "cocktail" of drugs used to suppress HIV calls for a doubling of the protease inhibitor component, researchers reported at the Fifth Conference on Retroviruses and Opportunistic Infections. Joseph P. Eron, MD, of the University of North Carolina, Chapel Hill, described a phase II open-label study comparing four regimens.

An investigational protease inhibitor, amprenavir (developed by Vertex and Glaxo Wellcome), was combined with each of three currently approved protease inhibitors, nelfinavir (Viracept), indinavir (Crixivan), and saquinavir (Invirase); the fourth regimen combined amprenavir with the nucleoside analogs lamivudine (Epivir) and zidovudine (Retrovir). Patients in the study had not previously been treated with protease inhibitors, had CD4 cell counts greater than 200, and had viral loads greater than 10,000 copies/mL.

Of 34 patients randomized in the trial, nine discontinued medication early (one due to adverse events); only patients who had completed 16 weeks of therapy at the time of the analysis are included in the report.

At 16 weeks, the amprenavir/indinavir combination resulted in median viral load declines of 3.75 logs, with 5 of 6 patients having undetectable levels (less than 400 copies/mL). The amprenavir/saquinavir arm showed a median 2.94 log drop in viral load, with 5 of 5 patients having undetectable virus, and the amprenavir/nelfinavir arm showed a median 1.84 log drop in virus, with 3 of 6 patients having undetectable virus. Amprenavir/lamivu-dine/zidovudine also showed good results, with a 2.79 log viral load drop and 2 of 3 patients having undetectable virus.

An ultrasensitive assay of HIV RNA (able to detect virus at a level of 20 copies/mL) was also performed at 16 weeks. Using this test, virus was undetectable in 4 of 6 patients in the amprenavir/indina-vir arm, 2 of 5 on amprenavir/saquinavir, 3 of 6 on amprenavir/nelfinavir, and 2 of 3 on amprenavir/lamivudine/zidovudine. Adverse events were generally mild and appeared to occur with similar frequency across the study arms.

"Despite the fact that this study is very small, the results suggest that double protease inhibitor combinations containing amprenavir are highly potent and may have promise in future regimens," Dr. Eron said.