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Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

Publication ,  Journal Article
Le, T; Chiarella, J; Simen, BB; Hanczaruk, B; Egholm, M; Landry, ML; Dieckhaus, K; Rosen, MI; Kozal, MJ
Published in: PLoS One
June 29, 2009

BACKGROUND: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). CONCLUSIONS/SIGNIFICANCE: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

June 29, 2009

Volume

4

Issue

6

Start / End Page

e6079

Location

United States

Related Subject Headings

  • Virus Replication
  • RNA, Viral
  • Prevalence
  • Odds Ratio
  • Mutation
  • Humans
  • HIV Infections
  • Genotype
  • General Science & Technology
  • Drug Resistance, Viral
 

Citation

APA
Chicago
ICMJE
MLA
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Le, T., Chiarella, J., Simen, B. B., Hanczaruk, B., Egholm, M., Landry, M. L., … Kozal, M. J. (2009). Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use. PLoS One, 4(6), e6079. https://doi.org/10.1371/journal.pone.0006079
Le, Thuy, Jennifer Chiarella, Birgitte B. Simen, Bozena Hanczaruk, Michael Egholm, Marie L. Landry, Kevin Dieckhaus, Marc I. Rosen, and Michael J. Kozal. “Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.PLoS One 4, no. 6 (June 29, 2009): e6079. https://doi.org/10.1371/journal.pone.0006079.
Le T, Chiarella J, Simen BB, Hanczaruk B, Egholm M, Landry ML, et al. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use. PLoS One. 2009 Jun 29;4(6):e6079.
Le, Thuy, et al. “Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.PLoS One, vol. 4, no. 6, June 2009, p. e6079. Pubmed, doi:10.1371/journal.pone.0006079.
Le T, Chiarella J, Simen BB, Hanczaruk B, Egholm M, Landry ML, Dieckhaus K, Rosen MI, Kozal MJ. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use. PLoS One. 2009 Jun 29;4(6):e6079.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

June 29, 2009

Volume

4

Issue

6

Start / End Page

e6079

Location

United States

Related Subject Headings

  • Virus Replication
  • RNA, Viral
  • Prevalence
  • Odds Ratio
  • Mutation
  • Humans
  • HIV Infections
  • Genotype
  • General Science & Technology
  • Drug Resistance, Viral