405   The Safety and Efficacy of a Ritonavir-Boosted Amprenavir-Based Regimen after Switch from Amprenavir-Based HAART.

M. Markowitz*¹, A. Hurley¹, B. Ramratnam¹, M. Louie¹, R. Kost¹, B. Captan¹, A. Pierce², M. Shaefer², L. Zhang¹, and D. D. Ho¹.
¹Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY and²Glaxo Wellcome, Res. Triangle Park, NC.

Background:RTV-boosted PI regimens afford advantages over single-PI HAART-based regimens. These include reduced pill burden, less frequent dosing intervals, and theoretically improved pharmacokinetics.

Methods:39 newly HIV-1-infected subjects were treated 33 days (range: 5—113) on average from the onset of symptoms of HIV-1 infection with an APV-based HAART regimen including ABC/3TC and IDV for the first 16 weeks.

Results:Median baseline values include log plasma HIV-1 RNA 5.31 (range: 2.7—6.8), CD4 503 cells/mm³(range: 222—1077), and CD8 1088 cells/mm³(range: 384—2833). Twenty-five of 39 subjects switched to APV 600 mg /r 100 mg every 12 h after a median of 48 weeks (range: 16—88) on study. Prior to switch, 4 subjects failed virologically (2 with MDR, 1 non-adherent, 1 with absent to low APV levels), 4 subjects discontinued therapy due to AEs and 4 were LTFU. Two continue on alternate HAART regimens. 33/39 (84.6%) subjects reached undetectable HIV-1 RNA levels 112 days on average (range: 5—279). After switch, 14 subjects reported improvement in ongoing AEs, 10 subjects reported no change and 1 subject reported a transient increase. No grade 3 or 4 laboratory AEs or significant changes in serum glucose, cholesterol, or ALT/AST have been observed post-switch. To assess antiviral activity we determined the number of "blips" per total observations once individuals reached plasma HIV-1 levels below 50 copies/ml. Of 218 observations in 25 subjects seen monthly pre-switch there were 20 episodes (9.2%) of isolated detectable plasma HIV-1 RNA measurements. Post-switch, of 94 observations in 25 subjects, there were 8 "blips" (8.5%). Preliminary PK determination of the median APV trough level post-switch in 12 subjects approximately 10.5 hours post-APV/rit dosing (range: 9— 13.5) was 1.62mg/ml (range: 0.49 to 2.68), 5-fold higher than APV levels at trough for a 1200 mg dose.

Conclusions:APV/rit-based HAART in doses of 600 mg/100 mg every 12 hours affords an improved adverse event profile, comparable antiviral activity, and superior PK when compared to APV-based HAART in a cohort of previously drug-naïve subjects.