Ultrasensitive detection of minor drug-resistant variants for HIV after nevirapine exposure using allele-specific PCR: clinical significance

AIDS Res Hum Retroviruses. 2010 Mar;26(3):293-300. doi: 10.1089/aid.2009.0082.

Abstract

HIV-1 drug resistance mutations have been detected at low frequencies after single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT). We investigated the relationship between these "minor variant" NVP-resistant viruses and clinical outcome with NVP-containing antiretroviral therapy (ART). An allele-specific quantitative PCR (ASPCR) assay was used to quantify the pre-ART frequency of K103N and Y181C in 26 women who had received sdNVP. The cohort was composed of 7 patients who experienced virologic failure and 19 control patients who maintained virologic suppression on NVP-containing ART; all were negative for resistance by standard genotyping. NVP resistance mutations were found in 17 of 26 (65%) patients using ASPCR. The frequency of NVP-resistant viruses ranged from 0.1% to 4.11%. Receiver operating characteristics (ROC) analysis identified a clinical threshold frequency of 0.19% for the ASPCR assay. Application of this threshold demonstrated minor variant resistance in 6 of 7 patients (86%) who failed treatment compared to 6 of 19 patients (32%) who were successful (OR = 13; 95% CI 1.27-133). ASPCR provides a means of detecting minor variant drug-resistant viruses that may impact subsequent treatment response. These data suggest a clinical role for highly sensitive assays to detect and quantify resistant viruses at low frequencies.

Publication types

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

MeSH terms

  • Botswana
  • Drug Resistance, Viral* / drug effects
  • Drug Resistance, Viral* / genetics
  • Female
  • Gene Frequency
  • Genetic Variation
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Nevirapine / therapeutic use*
  • Polymerase Chain Reaction / methods
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Complications, Infectious* / drug therapy
  • Pregnancy Complications, Infectious* / virology
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Sensitivity and Specificity
  • Time Factors
  • Treatment Outcome

Substances

  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Nevirapine