Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure.

Journal Article (Clinical Trial;Journal Article)

Changes in HIV tropism from R5 to non-R5 or development of drug resistance is often associated with virologic failure in patients treated with maraviroc, a CCR5 antagonist. We sought to examine changes in HIV envelope sequences and inferred tropism in patients who did not respond to maraviroc-based regimens. We selected 181 patients who experienced early virologic failure on maraviroc-containing therapy in the MOTIVATE trials. All patients had R5 HIV by the original Trofile assay before entry. We used population-based sequencing methods and the geno2pheno algorithm to examine changes in tropism and V3 sequences at the time of failure. Using deep sequencing, we assessed whether V3 sequences observed at failure emerged from preexisting subpopulations. From population genotyping data at failure, 90 patients had R5 results, and 91 had non-R5 results. Of the latter group, the geno2pheno false-positive rate (FPR) value fell from a median of 20 at screening to 1.1 at failure. By deep sequencing, the median percentage of non-R5 variants in these patients rose from 1.4% to 99.5% after a median of 4 weeks on maraviroc. In 70% of cases, deep sequencing could detect a pretreatment CXCR4-using subpopulation, which emerged at failure. Overall, there were two distinct patterns of failure of maraviroc. Patients failing with R5 generally had few V3 substitutions and low non-R5 prevalence by deep sequencing. Patients with non-R5 HIV who were failing developed very-high-prevalence non-R5 HIV (median, 99%) and had very low geno2pheno values.

Full Text

Duke Authors

Cited Authors

  • Swenson, LC; Chui, CKS; Brumme, CJ; Chan, D; Woods, CK; Mo, T; Dong, W; Chapman, D; Lewis, M; Demarest, JF; James, I; Portsmouth, S; Goodrich, J; Heera, J; Valdez, H; Harrigan, PR

Published Date

  • December 2013

Published In

Volume / Issue

  • 57 / 12

Start / End Page

  • 6122 - 6130

PubMed ID

  • 24080655

Pubmed Central ID

  • PMC3837924

Electronic International Standard Serial Number (EISSN)

  • 1098-6596

Digital Object Identifier (DOI)

  • 10.1128/AAC.01534-13


  • eng

Conference Location

  • United States