Continuous improvement in the immune system of HIV-infected children on prolonged antiretroviral therapy

AIDS. 2008 Nov 12;22(17):2267-77. doi: 10.1097/QAD.0b013e3283189bb3.

Abstract

Background: The goal of HAART is to promote reconstitution of CD4+ T cells and other immune responses. We evaluated the extent and the kinetics of immune reconstitution in HIV-infected children over 144 weeks of successful HAART.

Methods: Thirty-seven children receiving their first HAART regimen had plasma HIV RNA; T cells and subpopulations; T-cell rearrangement excision circles (TREC) DNA; candida, HIVCD4 and HIVCD8 enzyme-linked immunospot measured at regular intervals.

Results: Plasma HIV RNA became undetectable in 81% of patients at 24 weeks and remained undetectable in 77% at 144 weeks. In contrast, CD4+% continuously increased. Distribution of T-cell subpopulations changed rapidly during the first 48 weeks of HAART and more slowly thereafter. At 144 weeks, total, naive and activated CD4+% and naive CD8+% of HIV-infected children were not significantly different from those of healthy age-matched controls, whereas total and activated CD8+% remained elevated. CD4 and CD8 TREC content increased only during the first 48 weeks of HAART. They positively correlated with each other and with total CD4+%, naive CD4+% and naive CD8+%. Candida and HIVCD4 enzyme-linked immunospot increased over time reaching peak values at 48 weeks and 144 weeks, respectively. HIVCD8 enzyme-linked immunospot decreased in magnitude over 144 weeks of HAART but retained its breadth. Baseline CD4+% positively correlated with CD4+% and with functional immune reconstitution at week 144, whereas baseline TREC correlated with TREC at week 144.

Conclusion: HIV-infected children acquired normal distribution of CD4 T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of HAART.

Publication types

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

MeSH terms

  • Adolescent
  • Antiretroviral Therapy, Highly Active* / methods
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Female
  • Gene Rearrangement, T-Lymphocyte / physiology
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • HIV-1 / immunology*
  • Humans
  • Immune System / physiology
  • Longitudinal Studies
  • Male
  • Thymus Gland / immunology
  • Treatment Outcome
  • Viral Load
  • Virus Replication / physiology
  • Young Adult