E-mail Abstract Author Session Search Abstracts Program

Session 35a Oral Abstract Presentations
Clinical Trials and Cohorts
Session Day and Time: Friday 8:30 - 10:30 am
Presentation Time: 09:00
Room: Auditorium


178
The Context Study: Efficacy and Safety of GW433908/RTV in PI-experienced Subjects with Virological Failure (24 Week Results)
E DeJesus*1, A LaMarca2, M Sension3, C Beltran4, P Yeni5
1Infectious Disease Clin, Altamonte Springs, FL; 2TheraFirst Med, Ft Lauderdale, FL; 3N Broward Hosp Dist, Ft Lauderdale, FL; 4Hosp Trudeau, Santiago, Chile; and 5Hosp Bichat, Paris, France

Background: GW433908 (908) is an investigational protease inhibitor (PI) with demonstrated antiviral activity, durability, and tolerability in ART-naïve subjects. This study compared the efficacy and safety of 908/ritonavir (RTV) when dosed either once (QD) or twice (BID) daily vs lopinavir (LPV)/RTV BID in PI-experienced subjects over 48 weeks (wks).

Methods: The primary objective of this randomized, open label study was to assess antiviral response by measuring time averaged change in vRNA from baseline (AAUCMB) at both 24 and 48 wks. Each of the 908/RTV regimens was assessed for non-inferiority to LPV/RTV. We enrolled 320 (315 treated) PI experienced subjects (£ 2 prior PIs) with plasma HIV-1 RNA (vRNA) ≥1000 c/ml. Subjects were randomized 1:1:1 to 908/RTV 1400 mg/200 mg QD, 908/RTV 700 mg/100 mg BID or LPV/RTV 400 mg/100 mg BID. Each regimen included 2 active RTIs selected on the basis of resistance testing. The use of NNRTIs was prohibited.

Results: Baseline vRNA and CD4 counts were similar between arms with medians of 4.14 log10 c/ml and 263 cells/mm3, respectively. After 24 wks of treatment, the mean stratum adjusted difference (97.5% CI) in AAUCMB using an ITT observed analysis was 0.178 log10 c/ml (-0.069, 0.424) and 0.164 log10 c/ml (-0.087, 0.414) for 908/RTV QD vs LPV/RTV and 908/RTV BID vs LPV/RTV, respectively. The upper limits of both CIs were below the pre-specified 0.5 non-inferiority margin.

 

 

908/RTV QD

n = 105

908/RTV BID

n = 107

LPV/RTV BID

n = 103

Mean AAUCMB (log10 c/mL)a

-1.46

-1.48

-1.63

Median CD4 cells/mm3 D from BL

72

62

63

Drug-related Clinical AEs (³ Grade 2)

19%

35%

34%

Treatment-limiting AEs

3%

3%

6%

Grade 3/4 ALT and/or AST, > 5 ULNb

6%

6%

4%

Grade 3/4 Cholesterol, > 1.6 ULNb

0%

0%

0%

Grade 3/4 Triglycerides, > 750 mg/dLb

4%

8%

4%

a ITT observed; b Treatment emergent

 

Conclusions: The preliminary 24-wk results from this study of PI-experienced subjects with previous virological failure, demonstrate the non-inferiority of the 908/RTV arms to LPV/RTV as evidenced by the comparable AAUCMBs. All study drugs were generally well tolerated.