Homeostatic role of IL‐7 in HIV‐1 infected children on HAART: Association with immunological and virological parameters

Abstract

To investigate the role of IL-7 in HIV-infected children on highly active antiretroviral therapy (HAART) and its association with laboratory parameters related to disease progression. A cross-sectional study in 31 vertically HIV-infected children (median age 8.4 y) treated with HAART, and a longitudinal study in four of those same children was carried out. In both studies, viral load, CD4+ T-cell counts, thymic production of T cells by TCR rearrangement excision circles (TRECs), IL-7 plasma levels and viral phenotype were determined. IL-7 levels were higher in HIV-infected children than in age-matched, uninfected controls. In addition, HIV children with CD4+ T cells between 200 and 500 T cells/mm3 had higher IL-7 levels and lower TREC values than HIV-infected children with CD4+ T cells >500 T cells/mm3. IL-7 levels were higher in children with syncytium-inducing (SI) phenotype than in those with non-syncytium-inducing (NSI) variants. During the follow-up of four HIV children, the decrease in viral load after HAART was always associated with a recovery of CD4+ T cells and TRECs, which was followed by a decrease in IL-7 returning to the levels present prior to the drop in CD4+ T cells. The four HIV-infected children had SI/X4 isolates in PBMC before HAART, and the viral phenotype switched to NSI/R5 after HAART. Our data suggest that IL-7 plays a key role in the maintenance of T-cell homeostasis in HIV-infected children on HAART, both through peripheral expansion and through a thymus-dependent mechanism.