title: Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study.
abstract: BACKGROUND
  With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed.
  
  
  METHODS
  HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration. Clinical success was defined as WAZ and WAZ >-2, immunological success as CD4 cells ≥500/mm3 and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration <40 copies/mL.
  
  
  RESULTS
  Between March 2008 and December 2009, 123 HIV-infected children were included. The median (interquartile (IQR) age at cART initiation was 7.4 (3.2, 11.5) years; 40% were <5 years and 54% were female. Mean (95% confidence interval (95%CI)) HAZ and WAZ at baseline were -2.01 (-2.23, -1.80) and -1.73 (-1.95, -1.50) respectively and rose to -1.75 (-1.98, -1.51) and -1.17 (-1.38, -0.96) after 12 months of cART. The median (IQR) CD4 T-cell values for children <5 and ≥5 years of age were 20% (13, 28) and 337 (236, 484) cells/mm3 respectively, and increased to 36% (28, 41) and 620 (375, 880) cells/mm3. After 12 months of cART, 24% of children had a detectable viral load, including 16% with virological failure (HIV-RNA>1000 c/mL). Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33%) of children had side effects (by self-report or clinical assessment), but only 9% experienced a severe side effect requiring a cART regimen change.
  
  
  CONCLUSIONS
  cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as possible, optimizing adherence and optimizing management of side effects.
authors.affiliation: Kigali University Teaching Hospital, Department of Pediatrics, Kigali, Rwanda; Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Philippe R
authors.initials: PR
authors.lastname: Mutwa
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands; Biomedical Research, Epidemiology Unit, Royal Tropical Institute, Amsterdam, The Netherlands.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Boer
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Brenda
authors.initials: B
authors.lastname: Asiimwe-Kateera
authors.affiliation: Outpatients Clinic, Treatment and Research on HIV/AIDS Centre, Kigali, Rwanda.
authors.forename: Diane
authors.initials: D
authors.lastname: Tuyishimire
authors.affiliation: Kigali University Teaching Hospital, Department of Pediatrics, Kigali, Rwanda.
authors.forename: Narcisse
authors.initials: N
authors.lastname: Muganga
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands; Institute of Infection and Global Health, University of Liverpool, Liverpool, United of Kingdom; Rinda Ubuzima, Kigali, Rwanda.
authors.forename: Janneke
authors.initials: J
authors.lastname: van de Wijgert
authors.affiliation: Ministry of Health of Rwanda, Kigali, Rwanda.
authors.forename: Anita
authors.initials: A
authors.lastname: Asiimwe
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands; Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Sibyl P M
authors.initials: SP
authors.lastname: Geelen
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008297:Male; D055118:Medication Adherence; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012432:Rwanda / Q000453:epidemiology
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral