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

TitlePhenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsDerache A, Wallis CL, Vardhanabhuti S, Bartlett J, Kumarasamy N, Katzenstein D
JournalJ Infect Dis
Volume213
Issue2
Pagination250-6
Date Published2016 Jan 15
ISSN1537-6613
KeywordsAdult, Africa South of the Sahara, Anti-HIV Agents, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Male, Mutagenesis, Site-Directed, Phenotype, Thailand
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.

DOI10.1093/infdis/jiv383
Alternate JournalJ. Infect. Dis.
PubMed ID26175454
PubMed Central IDPMC4690149
Grant ListAI068634 / AI / NIAID NIH HHS / United States
R01 AI066922-01A2 / AI / NIAID NIH HHS / United States
U01069484 / / PHS HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI069432 / AI / NIAID NIH HHS / United States
U01AI069518 / AI / NIAID NIH HHS / United States
U01AI38858 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States