CD4+ T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy

Objective: The aim of this study was to analyze the association between CD4(+) depletion and immune activation in HIV-1-infected children on highly active antiretroviral therapy (HAART). Design and Setting: We carried out a cross-sectional study to determine the profile of several immunologic parameters in 143 children on HAART for more than 24 weeks. Children were stratified according to current immunologic status (CD4(+) < 15% 15%-25%, and >= 25%) and viral load (VL) levels (< 400 copies/mL, 400-10,000 copies/mL; and > 10,000 copies/mL). We also Studied 23 uninfected children as healthy controls. Methods: Viral load (HIV-RNA copies per milliliter) was quantified using reverse transcriptase polymerase chain reaction molecular assay. T-cell subsets were determined by multiparametric flow cytometry. Results: HIV-infected children with low percentage of CD4(+) had high memory (CD45RO(+)) and low naive (CD45RA(+)) CD4(+) and CD8(+) T-cell values. Furthermore, children with CD4(+) > 25% had similar memory and naive CD4(+) values as the healthy control group, whereas memory and naive CD8(+) subsets were different from the healthy control values. In these HIV-infected children, when CD4(+) was depleted, the amount of naive plus central memory CD8(+) (CD28(+)CD57(-)) cells was decreased, whereas effector CD8(+) (CD28(-)CD57(+)) cells were upregulated, and these values were always higher than healthy control values. Furthermore, children with low percentage of CD4(+) showed significant upregulation of HLA-DR(+)CD38(+) and HLA-DR+ in both CD4(+) and CD8(+) T-cells independent of VL levels. Conclusions: Our data suggest that elevated immune activation could be responsible for CD4(+) depletion rather than HIV replication because immunologic status is associated directly to immune activation and not to VL levels in HIV-infected children on HAART.