Background: Atazanavir (ATV) is a potent, safe, well-tolerated, once-daily azapeptide protease inhibitor (PI) in Phase III development that does not result in clinically relevant elevations in serum lipids. The objectives of the Phase II trial BMS AI424-044 are to assess the long-term efficacy and safety of ATV beyond 72 weeks and to assess efficacy and safety in patients switched from Nelfinavir (NFV) Þ Atazanavir (ATV).

Methods: Patients (pts) completing the Phase II trial BMS AI424-008 were eligible for treatment with ATV/Stavudine (d4T)/Lamivudine (3TC) in this ongoing, prospective, open-label, rollover/switch study. Pts on NFV were switched to ATV 400 mg; pts on ATV were continued on either ATV 400 mg or ATV 600 mg. HIV RNA levels, CD4 cell counts, and safety (including lipid parameters) were assessed.

Results: A total of 346 pts (63% male, 37% female) were enrolled and treated in AI424-044; the median cumulative time on therapy was approximately 108 weeks (~72 wks in AI424-008 and ~36 wks in AI424-044).

 

TC = total cholesterol, LDL-C = low-density lipoprotein cholesterol, TG = triglycerides

^†As treated analysis, results maintained through 108 wks from start of AI424-008. ITT analysis for 008/044 selected cohort

^‡p < 0.0001, NFVÞATV, mean % change, wk 24 vs entry

 

Discontinuations due to adverse events were infrequent and comparable across cohorts (ATV 400 mg, 1%; ATV 600 mg, 2%; NFV Þ ATV, 3%), and no new safety issues were identified after approximately 108 wks of cumulative ATV treatment in AI424-008/044. Asymptomatic elevation in indirect bilirubin (without hepatic transaminase elevation) was the most frequent laboratory abnormality.

Conclusions: Extended ATV treatment results in sustained virologic suppression and continued CD4 cell increase without clinically relevant increases in TC, fasting LDL-C, or fasting TG. After a switch from NFV, 24 wks of ATV treatment is associated with maintained or improved virologic suppression and results in significant decreases in TC, fasting LDL-C, and fasting TG towards pre-antiretroviral treatment levels.