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Evolution of drug-resistant viral populations during interruption of antiretroviral therapy.

Publication ,  Journal Article
Wang, D; Hicks, CB; Goswami, ND; Tafoya, E; Ribeiro, RM; Cai, F; Perelson, AS; Gao, F
Published in: J Virol
July 2011

Analysis of a large number of HIV-1 genomes at multiple time points after antiretroviral treatment (ART) interruption allows determination of the evolution of drug-resistant viruses and viral fitness in vivo in the absence of drug selection pressure. Using a parallel allele-specific sequencing (PASS) assay, potential primary drug-resistant mutations in five individual patients were studied by analyzing over 18,000 viral genomes. A three-phase evolution of drug-resistant viruses was observed after termination of ART. In the first phase, viruses carrying various combinations of multiple-drug-resistant (MDR) mutations predominated with each mutation persisting in relatively stable proportions while the overall number of resistant viruses gradually increased. In the second phase, viruses with linked MDR mutations rapidly became undetectable and single-drug-resistant (SDR) viruses emerged as minority populations while wild-type viruses quickly predominated. In the third phase, low-frequency SDR viruses remained detectable as long as 59 weeks after treatment interruption. Mathematical modeling showed that the loss in relative fitness increased with the number of mutations in each viral genome and that viruses with MDR mutations had lower fitness than viruses with SDR mutations. No single viral genome had seven or more drug resistance mutations, suggesting that such severely mutated viruses were too unfit to be detected or that the resistance gain offered by the seventh mutation did not outweigh its contribution to the overall fitness loss of the virus. These data provide a more comprehensive understanding of evolution and fitness of drug-resistant viruses in vivo and may lead to improved treatment strategies for ART-experienced patients.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 2011

Volume

85

Issue

13

Start / End Page

6403 / 6415

Location

United States

Related Subject Headings

  • Virology
  • Viral Load
  • Time Factors
  • Sequence Analysis, DNA
  • Reverse Transcriptase Inhibitors
  • Mutation
  • Humans
  • HIV-1
  • HIV Infections
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, D., Hicks, C. B., Goswami, N. D., Tafoya, E., Ribeiro, R. M., Cai, F., … Gao, F. (2011). Evolution of drug-resistant viral populations during interruption of antiretroviral therapy. J Virol, 85(13), 6403–6415. https://doi.org/10.1128/JVI.02389-10
Wang, Dongning, Charles B. Hicks, Neela D. Goswami, Emi Tafoya, Ruy M. Ribeiro, Fangping Cai, Alan S. Perelson, and Feng Gao. “Evolution of drug-resistant viral populations during interruption of antiretroviral therapy.J Virol 85, no. 13 (July 2011): 6403–15. https://doi.org/10.1128/JVI.02389-10.
Wang D, Hicks CB, Goswami ND, Tafoya E, Ribeiro RM, Cai F, et al. Evolution of drug-resistant viral populations during interruption of antiretroviral therapy. J Virol. 2011 Jul;85(13):6403–15.
Wang, Dongning, et al. “Evolution of drug-resistant viral populations during interruption of antiretroviral therapy.J Virol, vol. 85, no. 13, July 2011, pp. 6403–15. Pubmed, doi:10.1128/JVI.02389-10.
Wang D, Hicks CB, Goswami ND, Tafoya E, Ribeiro RM, Cai F, Perelson AS, Gao F. Evolution of drug-resistant viral populations during interruption of antiretroviral therapy. J Virol. 2011 Jul;85(13):6403–6415.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 2011

Volume

85

Issue

13

Start / End Page

6403 / 6415

Location

United States

Related Subject Headings

  • Virology
  • Viral Load
  • Time Factors
  • Sequence Analysis, DNA
  • Reverse Transcriptase Inhibitors
  • Mutation
  • Humans
  • HIV-1
  • HIV Infections
  • Genotype