Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results.

To compare the efficiency and safety of atazanavir and nelfinavir in antiretroviral-naive patients. Randomization to atazanavir 400 mg or 600 mg once daily; nelfinavir 1250 mg twice a day, plus lamivudine and stavudine. A blinded (to the atazanavir dose), 48-week trial in patients with HIV-1 RNA > or = 2000 copies/ml, CD4 cell count > or = 100 x 10(6) cells/l. Primary end-point: change in HIV-1 RNA from baseline at 48 weeks. Secondary end-point: subjects with HIV-1 RNA < 400, and < 50 copies/ml, CD4 cell count changes, adverse events. The 467 randomized subjects had comparable baseline characteristics across treatments. With atazanavir 400 mg, 600 mg and nelfinavir, respectively, mean changes in HIV-1 RNA (log10 copies/ml) from baseline to 48 weeks were -2.51, -2.58, -2.31; HIV-1 RNA < 400 copies/ml [intent-to-treat population (ITT), non-completion = failure (NC = F)], 64%, 67%, 53%; HIV-1 RNA < 50 copies/ml (ITT NC = F), 35%, 36%, 34%; mean CD4 cell count increased comparably at 48 weeks (234 x 10(6), 243 x 10(6), 211 x 10(6) cells/l). Adverse events were similar across treatments with the exception of diarrhea (more frequent with nelfinavir) and jaundice (more frequent with atazanavir). Mean changes from baseline to 48 weeks were: fasting low density lipoprotein cholesterol, +5.2%, +7.1% and +23.2% (at 56 weeks) and fasting triglycerides (48 weeks), +7.2%, +7.6% and +49.5%, in the atazanavir 400 mg, 600 mg, and nelfinavir groups, respectively (P < 0.01, atazanavir versus nelfinavir). Atazanavir is a potent, safe, well tolerated, and effective once-daily protease inhibitor with low pill burden (two capsules/day). Lipid changes with atazanavir were significantly less than with nelfinavir, however, clinical significance of these finding in terms of decreased cardiovascular risk is unknown.