title: Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis.
abstract: BACKGROUND
  In the Post Exposure Prophylaxis of Infants (PEPI)-Malawi trial, infants received up to 14 weeks of extended nevirapine (NVP) or extended NVP with zidovudine (NVP + ZDV) to prevent postnatal HIV transmission. We examined emergence and persistence of NVP resistance in HIV-infected infants who received these regimens prior to HIV diagnosis.
  
  
  METHODS
  Infant plasma samples collected at 14 weeks of age were tested using the ViroSeq HIV Genotyping System and a sensitive point mutation assay, LigAmp (for K103N and Y181C). Samples collected at 6 and 12 months of age were analyzed using LigAmp.
  
  
  RESULTS
  At 14 weeks of age, NVP resistance was detected in samples from 82 (75.9%) of 108 HIV-infected infants. Although the frequency of NVP resistance detected by ViroSeq was lower in the extended NVP + ZDV arm than in the extended NVP arm, the difference was not statistically significant (38/55 = 69.1% vs. 44/53 = 83.0%, P = 0.12). Similar results were obtained using LigAmp. Using LigAmp, the proportion of infants who still had detectable NVP resistance at 6 and 12 months was similar among infants in the two study arms (at 6 months: 17/20 = 85.0% for extended NVP vs. 21/26 = 80.8% for extended NVP + ZDV, P = 1.00; at 12 months: 9/16 = 56.3% for extended NVP vs.10/13 = 76.9% for extended NVP + ZDV, P = 0.43).
  
  
  CONCLUSIONS
  Infants exposed to extended NVP or extended NVP + ZDV had high rates of NVP resistance at 14 weeks of age, and resistant variants frequently persisted for 6-12 months. Frequency and persistence of NVP resistance did not differ significantly among infants who received extended NVP only vs. extended NVP + ZDV prophylaxis.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Fogel
authors.forename: Donald R
authors.initials: DR
authors.lastname: Hoover
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Mary G
authors.initials: MG
authors.lastname: Fowler
authors.forename: Allan W
authors.initials: AW
authors.lastname: Taylor
authors.forename: Newton
authors.initials: N
authors.lastname: Kumwenda
authors.forename: Taha E
authors.initials: TE
authors.lastname: Taha
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008295:Malawi; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage*; D056990:Post-Exposure Prophylaxis; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine; D019829:Nevirapine