Long-term effects of highly active antiretroviral therapy on CD4+ cell evolution among children and adolescents infected with HIV: 5 years and counting

Clin Infect Dis. 2008 Jun 1;46(11):1751-60. doi: 10.1086/587900.


Background: Lower percentages of CD4(+) T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4(+) lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4(+) cell percentage are maintained and whether they lead to normal CD4(+) cell percentages in children with severe immunosuppression.

Methods: The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4(+) cell percentage, using marginal structural models to account for confounding by severity.

Results: Initiation of any type of HAART increased CD4(+) cell percentage by 2.34% (95% confidence interval, 1.35%-3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4(+) cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4(+) cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4(+) cell percentage after 5 years of HAART did not reach normal levels.

Conclusions: Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4(+) cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active* / adverse effects
  • Biological Evolution
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes
  • Child
  • Child, Preschool
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV-1 / physiology*
  • Humans
  • Infectious Disease Transmission, Vertical
  • Time


  • Anti-HIV Agents