title: Nevirapine resistance by timing of HIV type 1 infection in infants treated with single-dose nevirapine.
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.
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Micek
authors.forename: Ana Judith
authors.initials: AJ
authors.lastname: Blanco
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Beck
authors.forename: Sandra
authors.initials: S
authors.lastname: Dross
authors.forename: Laurinda
authors.initials: L
authors.lastname: Matunha
authors.forename: Pablo
authors.initials: P
authors.lastname: Montoya
authors.forename: Kristy
authors.initials: K
authors.lastname: Seidel
authors.forename: Soren
authors.initials: S
authors.lastname: Gantt
authors.forename: Eduardo
authors.initials: E
authors.lastname: Matediane
authors.forename: Lilia
authors.initials: L
authors.lastname: Jamisse
authors.forename: Stephen
authors.initials: S
authors.lastname: Gloyd
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Frenkel
mesh_terms: D018890:Chemoprevention / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D009073:Mozambique; D019829:Nevirapine / Q000008:administration & dosage*; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D019829:Nevirapine
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