title: HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine.
abstract: OBJECTIVE
  To describe the prevalence of HIV-1 drug resistance mutations at the time of treatment initiation in a large cohort of HIV-infected children previously exposed to single-dose nevirapine (sdNVP) for prevention of transmission.
  
  
  METHODS
  Drug resistance mutations were measured pretreatment in 255 infants and young children under 2 years of age in South Africa exposed to sdNVP and initiating ritonavir-boosted lopinavir-based therapy. Those who achieved viral suppression were randomized to either continue the primary regimen or to switch to a nevirapine-based regimen. Pretreatment samples were tested using population sequencing and real time allele-specific PCR (AS-PCR) to detect Y181C and K103N minority variants. Those with confirmed viremia more than 1000 copies/ml by 52 weeks postrandomization in the switch group were defined as having viral failure.
  
  
  RESULTS
  Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, predominantly Y181C, were detected by either method in 62% of infants less than 6 months of age, in 39% of children 6-12 months of age, 22% 12-18 months, and 16% 18-24 months (P = <0.0001). NNRTI mutations detected by genotyping, but not K103N or Y181C mutations detected only by AS-PCR, were associated with viral failure in the switch group.
  
  
  CONCLUSIONS
  The prevalence of mutations known to compromise primary NNRTI-based therapy is high in sdNVP-exposed children, supporting current guidelines recommending use of protease inhibitor-based regimens for young children. Standard genotyping is adequate to identify children who could benefit from switching to NNRTI-based therapy.
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa. gillianh@nicd.ac.za
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Hunt
authors.forename: Ashraf
authors.initials: A
authors.lastname: Coovadia
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Gayle
authors.initials: G
authors.lastname: Sherman
authors.forename: Tammy
authors.initials: T
authors.lastname: Meyers
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
mesh_terms: D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000276:immunology*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012367:RNA, Viral; D013019:South Africa; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D019829:Nevirapine