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Abstract
Safety and Efficacy of Maraviroc (MVC), a Novel CCR5 Antagonist, When Used in Combination with Optimized Background Therapy (OBT) for the Treatment of Antiretroviral-Experienced Subjects Infected with Dual/Mixed-Tropic HIV-1: 24-Week Results of a Phase 2b Exploratory Trial
H. Mayer1, E. van der Ryst2, M. Saag3, B. Clotet4, G. Fatkenheuer5, N. Clumeck6, K. Turner2, J.M. Goodrich1
1Pfizer Global Research and Development, New London, United States, 2Pfizer Global Research and Development, Sandwich, United Kingdom, 3University of Alabama, Birmingham, United States, 4University Hospital Germans Trias i Pujol, Barcelona, Spain, 5University of Cologne, Cologne, Germany, 6St Pierre University Hospital, Brussels, Belgium
Background: Maraviroc (MVC) is a CCR5 antagonist active against R5 but not X4 or dual-tropic (R5/X4) HIV-1 in vitro. Patients with “dual-tropic” HIV generally are infected with a mixture of virus populations comprising R5, X4, and R5/X4 variants. This study was performed to determine the safety and efficacy of MVC, added to an optimised regimen (OBT) versus OBT alone, in patients with dual/mixed-tropic (D/M) infection.
Methods: A4001029 is an ongoing, double-blind, placebo-controlled trial. Subjects on a stable antiretroviral regimen, with non-R5 virus, HIV-1 RNA 5,000 c/mL and triple class experience and/or dual class resistant virus were randomized to one of three groups: OBT +/- MVC QD or BID. The primary endpoint was the change from baseline to 24 weeks in viral load (VL) for patients with D/M virus at screening, using an intent-to-treat analysis.
Results: Of 186 subjects with non-R5 virus randomized and treated, 167 had D/M virus at screening. Median baseline CD4 count was <50 cells/L and mean baseline VL was >5log10 c/mL for each treatment group. VL change from baseline to week 24 was similar for the MVC QD (-0.91 log10) and placebo groups (-0.97 log10) but slightly greater for the MVC BID group (-1.20 log10). Mean CD4 change was greater for the MVC groups: +60 and +62 cells/L, for QD and BID, respectively compared to +35 cells/L for placebo. Grade 3/4 adverse events, discontinuations and deaths occurred with similar frequency in all three groups. There were no cases of lymphoma or adenocarcinoma.
Conclusions: MVC was safe and well tolerated in this advanced population with documented D/M HIV-1 infection. While superiority of either MVC dose added on to OBT, versus OBT alone, was not achieved, there was no evidence of virological or immunological decline. In fact, a greater CD4 increase occurred in both MVC groups versus the placebo group, which requires further investigation.
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