Antiretroviral drug susceptibility among HIV-infected adults failing antiretroviral therapy in Rakai, Uganda

AIDS Res Hum Retroviruses. 2012 Dec;28(12):1739-44. doi: 10.1089/aid.2011.0352. Epub 2012 Apr 26.

Abstract

We analyzed antiretroviral drug susceptibility in HIV-infected adults failing first- and second-line antiretroviral treatment (ART) in Rakai, Uganda. Samples obtained from participants at baseline (pretreatment) and at the time of failure on first-line ART and second-line ART were analyzed using genotypic and phenotypic assays for antiretroviral drug resistance. Test results were obtained from 73 samples from 38 individuals (31 baseline samples, 36 first-line failure samples, and six second-line failure samples). Four (13%) of the 31 baseline samples had mutations associated with resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively). Among the 36 first-line failure samples, 31 (86%) had NNRTI resistance mutations and 29 (81%) had lamivudine resistance mutations; only eight (22%) had other NRTI resistance mutations. None of the six individuals failing a second-line protease inhibitor (PI)-based regimen had PI resistance mutations. Six (16%) of the participants had discordant genotypic and phenotypic test results. Genotypic resistance to drugs included in first-line ART regimens was detected prior to treatment and among participants failing first-line ART. PI resistance was not detected in individuals failing second-line ART. Surveillance for transmitted and acquired drug resistance remains a priority for scale-up of ART.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • Antiretroviral Therapy, Highly Active / methods*
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV / drug effects*
  • HIV / genetics*
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Protease / genetics
  • HIV Reverse Transcriptase / genetics
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation, Missense
  • Sequence Analysis, DNA
  • Treatment Failure
  • Uganda
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • HIV Reverse Transcriptase
  • HIV Protease

Associated data

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