Format

Send to

Choose Destination
See comment in PubMed Commons below
J Infect Dis. 2016 Jan 15;213(2):250-6. doi: 10.1093/infdis/jiv383. Epub 2015 Jul 14.

Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection.

Author information

  • 1Division of Infectious Diseases, Stanford University, California.
  • 2Department of Molecular Pathology, Lancet Laboratories and BARC-SA, Johannesburg, South Africa.
  • 3Harvard School of Public Health, Boston, Massachusetts.
  • 4Duke University Medical Center, Durham, North Carolina.
  • 5Y. R. Gaitonde Centre for AIDS Research and Education, Chennai, India.

Abstract

BACKGROUND:

Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure.

METHODS:

AIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations.

RESULTS:

Genotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI.

CONCLUSIONS:

Although genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype.

KEYWORDS:

2nd NNRTI generation; HIV; first-line failure; genotype/phenotype comparison; subtype C

PMID:
26175454
PMCID:
PMC4690149
DOI:
10.1093/infdis/jiv383
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center