title: Prospective long-term outcomes of a cohort of Ugandan children with laboratory monitoring during antiretroviral therapy.
abstract: BACKGROUND
  Treatment of HIV-1 infected Ugandan children with antiretroviral therapy (ART) is increasing, but few prospective long-term studies evaluating the treatment process have been reported. In this study, we sought to determine prospectively how consistent monitoring of HIV-1 RNA levels affects the ART treatment process.
  
  
  METHODS
  One hundred eight children initiating ART were enrolled into this study. These children had comprehensive laboratory monitoring, including HIV-1 RNA level determination and genotype analysis (where appropriate), CD4% plus absolute counts and safety laboratory measurements performed before starting therapy and at regular intervals after receiving ART. Kaplan-Meier statistics were used to examine predictors of survival and virologic failure. Viral genotype analysis was performed on samples obtained from children having virologic failure to determine the emergence of mutations.
  
  
  RESULTS
  Clinically, there was no difference in the 3-year survival between our cohort receiving consistent laboratory monitoring and a matched historical clinic cohort not routinely receiving laboratory monitoring. However, 34% of children receiving ART demonstrated virologic failure. Eleven of these children received second-line ART, and all responded with an undetectable HIV-1 RNA level and an increase in CD4 count. Children remaining on a failing antiretroviral regimen accumulated resistance mutations.
  
  
  CONCLUSIONS
  Our prospective long-term findings support the general use of monitoring HIV-1 RNA levels for the management of children on ART and the adoption of a clearer definition for virologic failure and better guidelines for managing children with unsuppressed HIV-1 RNA levels.
authors.affiliation: Baylor College of Medicine Bristol Myers Squibb Children's Clinical Centre of Excellence, Mulago Hospital Kampala, Uganda.
authors.forename: Adeodata
authors.initials: A
authors.lastname: Kekitiinwa
authors.forename: Alice R
authors.initials: AR
authors.lastname: Asiimwe
authors.forename: Philip
authors.initials: P
authors.lastname: Kasirye
authors.forename: Violet
authors.initials: V
authors.lastname: Korutaro
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kitaka
authors.forename: Albert
authors.initials: A
authors.lastname: Maganda
authors.forename: Michael
authors.initials: M
authors.lastname: Madalon
authors.forename: Frank M
authors.initials: FM
authors.lastname: Graziano
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral