title: Women exposed to single-dose nevirapine in successive pregnancies: effectiveness and nonnucleoside reverse transcriptase inhibitor resistance.
abstract: OBJECTIVE
  To assess the impact of prior exposure to single-dose nevirapine (sdNVP) on mother-to-child transmission and genotypic resistance in HIV-infected women.
  
  
  METHODS
  Prospective study of 120 women exposed to the HIVNET 012 sdNVP regimen in two successive pregnancies and 240 antiretroviral (ARV)-naïve, multiparous women who received sdNVP for the first time.
  
  
  RESULTS
  One hundred and eight of 120 and 193 of 240 women returned for a postpartum visit by 6 weeks. HIV-1 was detected in 11.1% (95% confidence interval = 5.9-18.6) of the infants of women previously exposed to sdNVP and 4.2% (95% confidence interval = 1.3-7.0) of those exposed for the first time (P = 0.028). Rates of maternal HIV-1 genotypic resistance at 6 weeks postdelivery were 37.5% and 46.4%, respectively (P = 0.119). Sensitive mutation-specific real-time PCR testing found three of 12 previously exposed women who transmitted HIV-1 to their infants had either K103N or Y181C at baseline compared with one of eight ARV-naïve, transmitting women who had Y181C. None of 40 randomly selected nontransmitting women from either group had detectable NVP resistance mutations prior to sdNVP exposure.
  
  
  CONCLUSIONS
  This study shows that effectiveness of sdNVP may be compromised by prior exposure to sdNVP, although the increase in transmission rate after prior exposure could not be explained by the detection of NVP resistance mutations prior to re-exposure as measured both by standard genotyping and highly sensitive allele-specific PCR assays. Furthermore, transmission rates of women with prior exposure were not higher than those reported elsewhere.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. neil1.martinson@gmail.com
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martinson
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Johnson
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.forename: Visva
authors.initials: V
authors.lastname: Pillay
authors.forename: Johanna
authors.initials: J
authors.lastname: Ledwaba
authors.forename: Puleng
authors.initials: P
authors.lastname: Dhlamini
authors.forename: Sarah
authors.initials: S
authors.lastname: Cohen
authors.forename: Adrian
authors.initials: A
authors.lastname: Puren
authors.forename: Jan
authors.initials: J
authors.lastname: Steyn
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
authors.forename: James A
authors.initials: JA
authors.lastname: McIntyre
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000276:immunology; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D019829:Nevirapine / Q000008:administration & dosage* / Q000276:immunology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine