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

Publication ,  Journal Article
Swenson, LC; Chui, CKS; Brumme, CJ; Chan, D; Woods, CK; Mo, T; Dong, W; Chapman, D; Lewis, M; Demarest, JF; James, I; Portsmouth, S; Heera, J ...
Published in: Antimicrob Agents Chemother
December 2013

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.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

December 2013

Volume

57

Issue

12

Start / End Page

6122 / 6130

Location

United States

Related Subject Headings

  • Viral Tropism
  • Triazoles
  • Treatment Failure
  • Receptors, CXCR4
  • Receptors, CCR5
  • Peptide Fragments
  • Middle Aged
  • Microbiology
  • Maraviroc
  • Male
 

Citation

APA
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MLA
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Swenson, L. C., Chui, C. K. S., Brumme, C. J., Chan, D., Woods, C. K., Mo, T., … Harrigan, P. R. (2013). Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure. Antimicrob Agents Chemother, 57(12), 6122–6130. https://doi.org/10.1128/AAC.01534-13
Swenson, Luke C., Celia K. S. Chui, Chanson J. Brumme, Dennison Chan, Conan K. Woods, Theresa Mo, Winnie Dong, et al. “Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure.Antimicrob Agents Chemother 57, no. 12 (December 2013): 6122–30. https://doi.org/10.1128/AAC.01534-13.
Swenson LC, Chui CKS, Brumme CJ, Chan D, Woods CK, Mo T, et al. Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure. Antimicrob Agents Chemother. 2013 Dec;57(12):6122–30.
Swenson, Luke C., et al. “Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure.Antimicrob Agents Chemother, vol. 57, no. 12, Dec. 2013, pp. 6122–30. Pubmed, doi:10.1128/AAC.01534-13.
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. Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure. Antimicrob Agents Chemother. 2013 Dec;57(12):6122–6130.

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

December 2013

Volume

57

Issue

12

Start / End Page

6122 / 6130

Location

United States

Related Subject Headings

  • Viral Tropism
  • Triazoles
  • Treatment Failure
  • Receptors, CXCR4
  • Receptors, CCR5
  • Peptide Fragments
  • Middle Aged
  • Microbiology
  • Maraviroc
  • Male