title: Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda.
abstract: BACKGROUND
  Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start.
  
  
  METHODS
  Cross-sectional assessment of all children treated with ART for 12 (M12) and 24 (M24) months was performed. CD4 counts, HIV RNA levels, antiretroviral resistance patterns, and non-nucleoside reverse transcriptase inhibitor (NNRTI) plasma concentrations were determined. Patient adherence and antiretroviral-related toxicity were assessed.
  
  
  RESULTS
  Cohort probabilities of retention in care were 0.86 at both M12 and M24. At survey, 71 (83%, M12) and 32 (78%, M24) children remained on therapy, and 84% participated in the survey. At ART start, 39 (45%) were female; median age was 5 years. Median initial CD4 percent was 11% [IQR 9-15] in children < 5 years old (n = 12); CD4 count was 151 cells/mm(3) [IQR 38-188] in those ≥ 5 years old (n = 26). At M12, median CD4 gains were 11% [IQR 10-14] in patients < 5 years old, and 206 cells/mm(3) [IQR 98-348] in ≥ 5 years old. At M24, median CD4 gains were 11% [IQR 5-17] and 132 cells/mm(3) [IQR 87-443], respectively. Viral suppression (< 400 copies/mL) was achieved in 59% (M12) and 33% (M24) of children. Antiretroviral resistance was found in 25% (M12) and 62% (M24) of children. Overall, 29% of patients had subtherapeutic NNRTI plasma concentrations.
  
  
  CONCLUSIONS
  After one year of therapy, satisfactory survival and immunological responses were observed, but nearly 1 in 4 children developed viral resistance and/or subtherapeutic plasma antiretroviral drug levels. Regular weight-adjustment dosing and strategies to reinforce and maintain ART adherence are essential to maximize duration of first-line therapy in children in resource-limited countries.
authors.affiliation: Clinical Research Department, Epicentre, Paris, France. laurence_ahoua@yahoo.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Ahoua
authors.forename: Gunar
authors.initials: G
authors.lastname: Guenther
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Loretxu
authors.initials: L
authors.lastname: Pinoges
authors.forename: Paul
authors.initials: P
authors.lastname: Anguzu
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.forename: Suna
authors.initials: S
authors.lastname: Balkan
authors.forename: David M
authors.initials: DM
authors.lastname: Olson
authors.forename: Charles
authors.initials: C
authors.lastname: Olaro
authors.forename: Mar
authors.initials: M
authors.lastname: Pujades-Rodríguez
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000097:blood; D012424:Rural Population; D014454:Uganda
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors