Long-term effects of highly active antiretroviral therapy on CD4+ cell evolution among children and adolescents infected with HIV: 5 years and counting.
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.
Patel
Kunjal
K
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. kpatel@hsph.harvard.edu
Hernán
Miguel A
MA
Williams
Paige L
PL
Seeger
John D
JD
McIntosh
Kenneth
K
Dyke
Russell B Van
RB
Seage
George R
GR
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D005075:Biological Evolution; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D013995:Time
D019380:Anti-HIV Agents