In vitro selection of clinically relevant bevirimat resistance mutations revealed by "deep" sequencing of serially passaged, quasispecies-containing recombinant HIV-1.

ABSTRACT: Initial in vitro studies of bevirimat resistance failed to observe mutations in the clinically significant QVT motif in SP1 of HIV-1 gag. This study presents a novel screening method involving mixed, clinically derived gag-protease recombinant HIV-1 samples to more accurately mimic the selection of resistance seen in vivo. Bevirimat resistance was investigated via population-based sequencing performed with a large, initially antiretroviral-naïve cohort before (n = 805) and after (n = 355) standard HIV therapy (without bevirimat). The prevalence of any polymorphism in the motif comprising Q, V, and T was ∼ 6%, 29%, and 12%, respectively, and did not change appreciably over the course of therapy. From these samples, three groups of 10 samples whose bulk sequences were wild type at the QVT mo

SUBMITTER: Knapp DJ 

PROVIDER: S-EPMC3020451 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature