Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen

Antivir Ther. 2008;13(1):135-9.

Abstract

Introduction: Emergence of nevirapine (NVP) resistance may be a consequence of its use in monotherapy to prevent HIV mother-to-child transmission (MTCT). The aim of this study was to evaluate the emergence of strains resistant to NVP and lamivudine (3TC) after discontinuation of antiretroviral therapy (ART) with 3TC/zidovudine (ZDV)/NVP.

Methods: Twenty pregnant women (ART-naive or preexposed only to ZDV), to whom 3TC/ZDV/NVP was prescribed as MTCT prophylaxis, were studied. They received ART for a median of 4 months with median viral load (VL) at labour <50 copies/ml. Samples were collected between 1 and 15 months (median: 3 months) after ART interruption. Sequence-selective real-time PCR (SPCR), which quantifies minority viral populations containing K103N, Y181C and M184V mutations, and standard genotypic sequencing were assayed.

Results: No mutations associated with resistance to 3TC or NVP were found by standard population sequencing. Analysis of K103N by SPCR showed that 35% of the patients contained < or =0.1% of viruses carrying either the AAC or AAT mutations. For Y181C mutation, 10% of the patients contained <0.5% of viruses with TGT codon change. For M184V mutation, one patient contained 6.2% of virus with GTG mutation and 13 patients (65%) contained <0.9% of mutated viruses. Four women were re-exposed to 3TC/ZDV/NVP and achieved HIV VL <50 copies/ml. No perinatal transmission occurred in any of the 22 births.

Conclusions: NVP associated with ZDV/3TC as a regimen to prevent MTCT may involve a low risk for the selection of antiretroviral-resistant strains and may not jeopardize the use of these same drugs for future treatment.

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • DNA, Viral / genetics
  • Drug Administration Schedule
  • Drug Resistance, Multiple, Viral / drug effects*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Lamivudine / administration & dosage*
  • Lamivudine / pharmacology*
  • Lamivudine / therapeutic use
  • Mutation
  • Nevirapine / administration & dosage*
  • Nevirapine / pharmacology*
  • Nevirapine / therapeutic use
  • Postpartum Period
  • Pregnancy

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Lamivudine
  • Nevirapine