HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy

Abstract

SUMMARY The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11·8 ± 0·4 (9·9; 15·4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0·05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4+ T cell absolute counts (r = 0·558; P = 0·05) and percentages (r = 0·625; P = 0·030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4+ and CD8+ T cell subsets were increased significantly (P < 0·05). CD4+ CD45RAhi+ CD62L+, CD4+ CD45RA+ and CD4+ CD38+ percentages, and the CD8+ CD45RAhi+ CD62L+ counts reached similar values to the control group. Also, CD8+ CD45RO+ CD38+ and CD8+ CD45RO+ percentages, and CD8+ CD45RO+ CD38+ absolute counts (P < 0·05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-α and interferon (IFN)-γ production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0·001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG1 and IgG3 plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.