title: Long-term effectiveness of combination antiretroviral therapy and prevalence of HIV drug resistance in HIV-1-infected children and adolescents in Rwanda.
abstract: OBJECTIVE
  To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy.
  
  
  METHODS
  A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed.
  
  
  RESULTS
  Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%).
  
  
  CONCLUSIONS
  Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.
authors.affiliation: From the *Department of Pediatrics, Kigali University Teaching Hospital; †Academic Medical Centre/Amsterdam Institute for Global Health and Development, Kigali, Rwanda; ‡Academic Medical Centre/Amsterdam Institute for Global Health and Development; §Royal Tropical Institute (KIT), Biomedical Research, Epidemiology Unit, Amsterdam, The Netherlands; ¶National Reference Laboratory; ‖Treatment and Research on HIV/AIDS Centre (TRAC-plus), Outpatients clinic, Kigali, Rwanda; **Department of Virology, University Medical Centre; and ††Utrecht University Children's Hospital/University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Philippe R
authors.initials: PR
authors.lastname: Mutwa
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Boer
authors.forename: John
authors.initials: J
authors.lastname: Rusine
authors.forename: Narcisse
authors.initials: N
authors.lastname: Muganga
authors.forename: Diane
authors.initials: D
authors.lastname: Tuyishimire
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Sibyl P M
authors.initials: SP
authors.lastname: Geelen
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008297:Male; D015995:Prevalence; D012432:Rwanda / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents