title: Long-term outcome of children receiving antiretroviral treatment in rural South Africa: substantial virologic failure on first-line treatment.
abstract: BACKGROUND
  Long-term (>12 months follow-up) virologic data of children receiving antiretroviral therapy (ART) in Sub-Saharan Africa are limited. Data from rural areas are especially scarce. The aim of this study was to evaluate the long-term virologic outcome of a pediatric cohort in rural South Africa.
  
  
  METHODS
  We performed a retrospective, observational cohort study, including children who initiated ART at least 1 year before data-analysis. Regular monitoring, including HIV-RNA testing, was performed. Genotypic resistance testing was done for children with virologic failure (HIV-RNA >1000 copies/mL). Logistic regression analysis was used to determine predictors of virologic failure.
  
  
  RESULTS
  A total of 101 children were included. Median duration since beginning ART was 31 months. Overall patient retention-rate was 76% (77/101), with early mortality being the main cause of attrition (13/24, 54%). Initial immunologic and virologic responses were excellent. However, 38% (31/81) of children subsequently experienced virologic failure. Correlation between virologic failure and immunologic decline was nearly absent. At the time of failure, multiple non-nucleoside reverse transcription inhibitor-associated mutations were observed in 52% (12/23) of children. No definite predictors of virologic failure could be determined.
  
  
  CONCLUSIONS
  ART provides significant benefits for children in this rural African setting, but the finding that a large proportion of children had virologic failure and developed major drug-resistance mutations on first-line ART is worrying. Causes of failure need to be analyzed and effective prevention strategies are needed. Because of the lack of a correlation between immunologic and virologic failure, treatment failure generally stays unnoticed in settings where HIV-RNA testing is not available.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands. r.e.barth@umcutrecht.nl
authors.forename: Roos E
authors.initials: RE
authors.lastname: Barth
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Tempelman
authors.forename: Elbert
authors.initials: E
authors.lastname: Smelt
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: Andy I
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Sibyl P
authors.initials: SP
authors.lastname: Geelen
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008137:Longitudinal Studies; D059012:Lost to Follow-Up; D055118:Medication Adherence; D009154:Mutation; D012189:Retrospective Studies; D012424:Rural Population; D013019:South Africa; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents