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


CONCLUSIONS
HIV-infected children acquired normal distribution of CD4 T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of HAART.
Weinberg
Adriana
A
University of Colorado Denver School of Medicine, Denver, Colorado, USA. Adriana.Weinberg@uchsc.edu
Dickover
Ruth
R
Britto
Paula
P
Hu
Chengcheng
C
Patterson-Bartlett
Julie
J
Kraimer
Joyce
J
Gutzman
Howard
H
Shearer
William T
WT
Rathore
Mobeen
M
McKinney
Ross
R
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D013950:Thymus Gland / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology; D055815:Young Adult