Evolution of CCR5 antagonist resistance in an HIV-1 subtype C clinical isolate.

ABSTRACT:

Objectives

We previously reported vicriviroc (VCV) resistance in an HIV-infected subject and used deep sequencing and clonal analyses to track the evolution of V3 sequence forms over 28 weeks of therapy. Here, we test the contribution of gp120 mutations to CCR5 antagonist resistance and investigate why certain minority V3 variants emerged as the dominant species under drug pressure.

Methods

Nineteen site-directed HIV-1 mutants were generated that contained gp120 VCV resistance mutations. Viral sensitivities to VCV, maraviroc, TAK-779, and HGS004 were determined.

Results

Three patterns of susceptibilities were observed as follows: sigmoid inhibition curves with 50% inhibitory concentration similar to pretreatment virus [07J-week 0 (W0)], single mutants with decreased 5

SUBMITTER: Henrich TJ 

PROVIDER: S-EPMC3070184 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature