Dose-Ranging, Randomized, Clinical Trial of Atazanavir with Lamivudine and Stavudine in Antiretroviral-Naïve Subjects: 48-Week Results
Robert L. Murphy, Ian Sannea, Pedro Cahn, Praphan Phanuphak, Lisa Percival, Thomas Kelleher, Michael Giordano
Northwestern University, 676 N. Saint Clair Street, Suite 200, Chicago, Illinois 60611, USA
Objective: To compare the efficiency and safety of atazanavir and nelfinavir in antiretroviral-naive patients.Design: Randomization to atazanavir 400 mg or 600 mg once daily; nelfinavir 1250 mg twice a day, plus lamivudine and stavudine.Methods: A blinded (to the atazanavir dose), 48-week trial in patients with HIV-1 RNA > 2000 copies/ml, CD4 cell count > 100 3 106cells/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.Results: 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), noncompletion 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 3 106, 243 3 106, 211 3 106cells/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 versusnelfinavir).Conclusions: 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.
AIDS Care ปี 2546, December ปีที่: 17 ฉบับที่ 5 หน้า 2603-2614
disease, inhibitors, therapy, Antiretroviral, active, Atazanavir, Cardiovascular, Highly, Hyperlipidemia, Protease