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Results of a Phase 2 Clinical Trial at 48 Weeks (AI424-007): A Dose-Ranging, Safety, and Efficacy Comparative Trial of Atazanavir at Three Doses in Combination with Didanosine and Stavudine in Antiretroviral-Naive Subjects

Sanne Ian; Piliero, Peter; Squires, Kathleen; Thiry, Alexandra; Schnittman, Steven; for the AI424-007 Clinical Trial Group
JAIDS Journal of Acquired Immune Deficiency Syndromes: January 2003

Three dose levels of the protease inhibitor (PI) atazanavir (200, 400, and 500 mg once daily) were compared with nelfinavir (750 mg three times daily) when given both as monotherapy and in combination with didanosine and stavudine in 420 antiretroviral-naive subjects infected with HIV-1. Subjects received monotherapy for 2 weeks, followed by combination therapy for 46 weeks. After 48 weeks, mean change from baseline in HIV RNA (-2.57 to -2.33 log10 copies/mL), the proportion of subjects with HIV RNA <400 copies/mL (56%-64%) and <50 copies/mL (28%-42%), and mean increases in CD4 cell count (185-221 cells/mm3) were comparable across treatment groups. Diarrhea was two to three times more common in the nelfinavir group (61% of subjects) than in the atazanavir groups (23%-30% of subjects, p < .0001 versus nelfinavir), and jaundice occurred only in atazanavir-treated subjects (6%, 6%, and 12% in the 200-, 400-, and 500-mg groups, respectively) (p < .03 for all atazanavir regimens vs. nelfinavir). Mean percent change from baseline in fasting low-density lipoprotein (LDL) cholesterol was significantly less in the atazanavir groups (-7% to 4%) than in the nelfinavir group (31%) (p < .0001). In conclusion, once-daily atazanavir is a potent, safe, and well tolerated PI that rapidly and durably suppresses HIV RNA and durably increases CD4 cell count in antiretroviral-naive subjects. Through 48 weeks, atazanavir was not associated with clinically relevant increases in total cholesterol, fasting LDL cholesterol, or fasting triglycerides. In comparison, nelfinavir was associated with prompt, marked, and sustained elevations in these parameters of a magnitude that suggests they are clinically relevant.

This study was funded by unrestricted educational grants from Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, and Triangle Pharmaceuticals; by clinical trials projects from Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, Triangle, Ketyx, Arones, and Pharma Natura; by a consulting agreement with Triangle Pharmaceuticals; and by the World AIDS Foundation.

Address correspondence and reprint requests to Ian Sanne, WHC Infectious Diseases Clinical Trials Unit, 27 Eton Road, Parktown, Johannesburg, South Africa 2193; e-mail:

Manuscript received July 23, 2002; accepted October 22, 2002.

© 2003 Lippincott Williams & Wilkins, Inc.