Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine

J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):148-53. doi: 10.1097/QAI.0b013e31802b920e.

Abstract

Background: Single-dose nevirapine (sd-NVP) is the mainstay of prevention of mother-to-child transmission programs in developing countries. Exposure to sd-NVP selects for resistance mutations, however. We longitudinally assessed these mutations in HIV-1-infected infants from Soweto and Durban, South Africa.

Methods: We prospectively followed 465 infants who received sd-NVP after enrolling their mothers when pregnant. If HIV infected, their virus was genotyped, using the ViroSeq HIV-1 Genotyping System, to detect resistant mutations. Those with resistance were genotyped at 6 months and then every 6 months out to 18 months if resistance was detected at the previous visit.

Results: Of 53 HIV-infected infants, 24 (45.3%) had detectable resistance at their first visit, when the most frequent mutations were Y181C (75%), K103N (25%), and Y188C (12%). Of those whose visit was before 12 weeks of age, 2 of 42 infants shared identical resistance mutations with their mothers. By 18 months of age, 11 of 24 infants with resistance had died and 1 still had the Y181C mutation.

Conclusions: Resistant mutations were selected in half of the infants exposed to sd-NVP, but fewer were detected over time and, unlike the case in their mothers, Y181C dominated initially and persists. Transient resistance mutations may have a negative impact on highly active antiretroviral therapy in infants and children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Female
  • HIV / classification
  • HIV / drug effects*
  • HIV / genetics
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / prevention & control
  • HIV Infections / transmission
  • HIV Infections / virology*
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical / prevention & control
  • Longitudinal Studies
  • Mutation
  • Nevirapine / administration & dosage
  • Nevirapine / therapeutic use*
  • Phylogeny
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / virology
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Sequence Homology
  • South Africa

Substances

  • Anti-HIV Agents
  • Nevirapine