HIV This Week

Weinberg A, Dickover R, Britto P, Hu C, Patterson-Bartlett J, Kraimer J, Gutzman H, Shearer WT, Rathore M, McKinney R; PACTG 1021 team. Continuous improvement in the immune system of HIV-infected children on prolonged antiretroviral therapy. AIDS. 2008;22(17):2267-77.

The goal of antiretroviral treatment is to promote reconstitution of CD4+ T cells and other immune responses. Weinberg and colleagues evaluated the extent and the kinetics of immune reconstitution in HIV-infected children over 144 weeks of successful antiretroviral treatment. Thirty-seven children receiving their first antiretroviral treatment 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. 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 antiretroviral treatment 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 antiretroviral treatment. 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 antiretroviral treatment 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. The authors concluded that HIV-infected children acquired normal distribution of CD4 T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of antiretroviral treatment.

Editors' note: This study is the first to demonstrate complete normalisation of T-cell subpopulations in children on antiretroviral treatment for 3 years, with the exception of elevated activated CD8+ percentage, which possibly may be due to low-level viral replication. CD4+ percentage was used as the main parameter in these analyses because it does not vary with the age of children whereas CD4 cell counts do. Given that both higher baseline CD4+ percentage and TREC levels indicating higher thymus function at treatment initiation predicted more robust immune reconstitution, it is clear that earlier HIV diagnosis and earlier antiretroviral treatment initiation in infants, combined with attention to adherence and monitoring of side effects, improve paediatric prognosis.