Development of phenotypic HIV-1 drug resistance after exposure to single-dose nevirapine

Adriaan E. Basson, Matshediso Ntsala, Neil Martinson, Emily Tlale, Gary E. Corrigan, Xingwu Shao, Glenda Gray, James McIntyre, Adrian Puren, Lynn Morris

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of HIV-I results in the selection of genotypic drug resistance mutations. To assess the levels of phenotypic resistance conferred by these mutations, we examined the ability of sample-derived HIV-I reverse transcriptase to function in the presence of nevirapine (NVP). Methods: Plasma samples from HIV-I pregnant women before and after exposure to sdNVP were used to extract viral reverse transcriptase for the Cavidi ExaVir Drug susceptibility assay. The fold increases in phenotypic resistance for each sample were compared with the genotypic profiles determined by population-based sequencing. Results: None of the women sampled before sdNVP exposure had phenotypic resistance (median fold increase 0.7). Seven weeks after sdNVP, there was a 16-fold increase in phenotypic resistance among women who had NVP resistance mutations compared with only a 1.9-fold increase among NVP-exposed women with wild-type virus. Phenotypic resistance decayed with time coincident with the fading of genotypic mutations, and by 18 months, all samples were phenotypically susceptible. Conclusions: Exposure of pregnant women to sdNVP was associated with the transient appearance of viral populations that displayed phenotypic resistance to NVR Overall, there was good concordance between phenotypic resistance to NVP, as measured with this enzymatic assay, and the presence of NVP genotypic mutations.

Original languageEnglish (US)
Pages (from-to)538-543
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume49
Issue number5
DOIs
StatePublished - Dec 2008

Keywords

  • Genotypic resistance
  • HIV-1 subtype C
  • Mother-to-child transmission
  • Nevirapine
  • Phenotypic resistance

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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