title: Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital.
abstract: OBJECTIVE
  To assess long-term virological efficacy and the emergence of drug resistance in children who receive antiretroviral treatment (ART) in rural Tanzania.
  
  
  METHODS
  Haydom Lutheran Hospital has provided ART to HIV-infected individuals since 2003. From February through May 2009, a cross-sectional virological efficacy survey was conducted among children (<15 years) who had completed >or=6 months of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Genotypic resistance was determined in those with a viral load of >200 copies/mL.
  
  
  RESULTS
  Virological response was measured in 19 of 23 eligible children; 8 of 19 were girls and median age at ART initiation was 5 years (range 2-14 years). Median duration of ART at the time of the survey was 40 months (range 11-61 months). Only 8 children were virologically suppressed (<or=40 copies/mL), whereas 11 children had clinically relevant resistance mutations in the reverse transcriptase gene. The most frequent mutations were M184V (n = 11), conferring resistance to lamivudine and emtricitabine, and Y181C (n = 4), G190A/S (n = 4) and K103N (n = 4), conferring resistance to NNRTIs. Of concern, three children had thymidine analogue mutations, associated with cross-resistance to all nucleoside reverse transcriptase inhibitors. Despite widespread resistance, however, only one child experienced a new WHO stage 4 event and none had a CD4 cell count of <200 cells/mm(3).
  
  
  CONCLUSIONS
  Among children on long-term ART in rural Tanzania, >50% harboured drug resistance. Results for children were markedly poorer than for adults attending the same programme, underscoring the need for improved treatment strategies for children in resource-limited settings.
authors.affiliation: Department of Infectious Diseases, Oslo University Hospital, Ulleval, Oslo, Norway.
authors.forename: Clara
authors.initials: C
authors.lastname: Bratholm
authors.forename: Asgeir
authors.initials: A
authors.lastname: Johannessen
authors.forename: Ezra
authors.initials: E
authors.lastname: Naman
authors.forename: Svein G
authors.initials: SG
authors.lastname: Gundersen
authors.forename: Sokoine L
authors.initials: SL
authors.lastname: Kivuyo
authors.forename: Mona
authors.initials: M
authors.lastname: Holberg-Petersen
authors.forename: Vidar
authors.initials: V
authors.lastname: Ormaasen
authors.forename: Johan N
authors.initials: JN
authors.lastname: Bruun
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D015658:HIV Infections / Q000188:drug therapy*; D006761:Hospitals; D006801:Humans; D008297:Male; D015995:Prevalence; D012424:Rural Population; D013636:Tanzania; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents