Nevirapine resistance by timing of HIV type 1 infection in infants treated with single-dose nevirapine

Clin Infect Dis. 2010 May 15;50(10):1405-14. doi: 10.1086/652151.

Abstract

Background: In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection.

Methods: We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time.

Results: Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P = .006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P = .001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P = .017, compared with established in utero infection).

Conclusions: The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals.

Publication types

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

MeSH terms

  • Chemoprevention / methods*
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / diagnosis*
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Male
  • Mozambique
  • Nevirapine / administration & dosage*
  • Prospective Studies
  • Time Factors

Substances

  • Nevirapine