Comparison of Once-Daily Atazanavir With Efavirenz, Each in Combination With Fixed-Dose Zidovudine and Lamivudine, As Initial Therapy for Patients Infected With HIV.
Squires, Kathleen MD *; Lazzarin, Adriano MD +; Gatell, Jose M. MD, PhD ++; Powderly, William G. MD [S]; Pokrovskiy, Vadim MD, PhD ||; Delfraissy, Jean-Francois MD [P]; Jemsek, Joseph MD #; Rivero, Antonio MD **; Rozenbaum, Willy MD ++; Schrader, Shannon MD ++++; Sension, Michael MD [S][S]; Vibhagool, Asda MD ||||; Thiry, Alexandra PhD [P][P]; Giordano, Michael MD [P][P]
[Article]
JAIDS Journal of Acquired Immune Deficiency Syndromes.
36(5):1011-1019, August 15, 2004.
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Background: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia.
Methods: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48.
Results: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm3 with atazanavir, 160 cells/mm3 with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels.
Conclusions: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.
(C) 2004 Lippincott Williams & Wilkins, Inc.
