title: Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study.
abstract: BACKGROUND
  Previous observational studies found highly active antiretroviral therapy (HAART) to be associated with improved survival among human immunodeficiency virus (HIV)-infected children and adolescents. However, these studies had limited follow-up of HIV-infected children undergoing HAART. Given that HIV infection is chronic and that exposure to HAART is likely to be life-long, there is a need to evaluate the long-term effect of HAART on survival in this population.
  
  
  METHODS
  The study included 1236 children and adolescents who were perinatally infected with HIV, who were on study or enrolled after January 1996 in a United States-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C), and who were not receiving HAART at baseline; subjects were observed for a maximum of 10 years through June 2006. A weighted Cox regression model was used to estimate the effect of HAART on survival, appropriately adjusted for time-varying confounding by severity.
  
  
  RESULTS
  At the end of the 10-year follow-up period (median duration of follow-up, 6.3 years; interquartile range, 4.3-9.8 years), 70% of participants had initiated HAART. Lower CD4 cell percentages, total lymphocyte counts, and albumin levels were associated with an increased probability of initiating HAART. Eighty-five deaths were observed, and the mortality hazard ratio associated with HAART, compared with non-HAART regimens, was 0.24 after adjusting for measured confounding by severity (95% confidence interval, 0.11-0.51).
  
  
  CONCLUSIONS
  The use of HAART was highly effective in reducing mortality during the period 1996-2006 among children and adolescents infected with HIV. With improved long-term survival, continued follow-up is necessary to evaluate the effects of prolonged use of HAART on potential adverse events, immune function, growth, sexual maturation, and quality of life in this population.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. kpatel@hsph.harvard.edu
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: John D
authors.initials: JD
authors.lastname: Seeger
authors.forename: Kenneth
authors.initials: K
authors.lastname: McIntosh
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018655:Lymphocyte Count; D008297:Male; D016016:Proportional Hazards Models; D012709:Serum Albumin / Q000032:analysis; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D012709:Serum Albumin