Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012

J Infect Dis. 2005 Jul 1;192(1):24-9. doi: 10.1086/430742. Epub 2005 Jun 1.

Abstract

Background: The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP.

Methods: We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT.

Results: ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay.

Conclusions: K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology*
  • Drug Administration Schedule
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical / prevention & control
  • Mutation
  • Nevirapine / administration & dosage
  • Nevirapine / pharmacology*
  • Pregnancy
  • Time Factors
  • Viral Proteins / genetics

Substances

  • Anti-HIV Agents
  • Viral Proteins
  • Nevirapine