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

Neil A. Martinson, Lynn Morris, Glenda Gray, Daya Moodley, Visva Pillay, Sarah Cohen, Puleng Dhlamini, Adrian Puren, Schene Bhayroo, Jan Steyn, James A. McIntyre

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)148-153
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume44
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • HIV-1 subtype C
  • K103N
  • Mother-to-child
  • Nevirapine
  • Nonnucleoside reverse transcriptase inhibitor
  • Resistance
  • South Africa
  • Y181C

ASJC Scopus subject areas

  • Virology
  • Immunology

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