Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study

Clin Infect Dis. 2008 Feb 15;46(4):507-15. doi: 10.1086/526524.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / mortality*
  • Humans
  • Infant
  • Infant, Newborn
  • Lymphocyte Count
  • Male
  • Proportional Hazards Models
  • Serum Albumin / analysis
  • Survival Analysis*
  • Treatment Outcome
  • United States


  • Anti-HIV Agents
  • Serum Albumin