Changes in Cellular Immune Activation and Memory T-Cell Subsets in HIV-Infected Zambian Children Receiving HAART

Abstract

Background Increased exposure to a broad array of pathogens in children residing in sub-Saharan Africa may lead to heightened immune activation and increased proportions of memory T cells. Changes in the size of these cellular subsets have implications for restoration of normal immune function after treatment with HAART and are not well-characterized in young sub-Saharan African children. Methods CD4+ and CD8+ T cell subsets were measured by flow cytometry in 157 HIV-infected Zambian children before and at 3-month intervals during HAART for up to 30 months and in 34 control children at a single study visit. Results Prior to HAART, HIV-infected children had higher levels of activated and effector memory (EM) CD4+ and CD8+ T cells, and lower levels of naïve T cells and CD8+ T cells expressing IL-7Rα, compared to control children. The median duration of follow-up was 14.9 months (IQR: 6.4, 23.2) among 120 HIV-infected children with at least one study follow-up visit. Levels of immune activation and EM CD4+ T cells declined within six months of HAART but the percentages of EM CD4+ T cells and effector CD8+ T cells remained elevated through 30 months of HAART. IL-7Rα-expressing CD8+ T cells increased with HAART, suggesting expansion of memory capacity. Conclusions HAART significantly reduced levels of immune activation and EM CD4+ T cells, and promoted reconstitution of naïve T cells and IL-7Rα-expressing CD8+ T cells. However, persistently high levels of EM CD4+ T cells in HIV-infected children may reflect chronic perturbations in T cell subset composition.

Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset

“…This subset is depleted in perinatally-infected infants with advanced disease. Here ART initiation results in a slow recovery of both CD8 + and CD4 + naïve T cells, with concomitant reduction of the effector memory T subsets and CD38+/HLA-DR+ activated T cells [ 53 ]. Early ART initiation preserves memory T and B compartment in pediatric cohorts [ 54 , 55 ].…”

Amino Acid Concentrations in HIV-Infected Youth Compared to Healthy Controls and Associations with CD4 Counts and Inflammation

“…Notably, amino acid concentrations have not been evaluated in HIV-infected children and young adults, a group whose metabolic needs are considerably different than in the adult population, 20 yet still suffer from HIV-related comorbidities and immune dysfunction despite cART. [21][22][23][24] Focusing on this younger population offers an opportunity for disease prevention and mitigation, as opposed to treatment of an established disease. Thus, the primary purpose of this observational study was to evaluate amino acid concentrations in HIV-infected children and young adults.…”

Measles and Rubella Seroprevalence Among HIV–infected and Uninfected Zambian Youth

“…While antiretroviral treatment (ART) reverses some of the immunologic damage due to HIV infection, 16,17 immunity to vaccine-preventable diseases does not appear to be restored, 18,19 as immune reconstitution in children primarily occurs with naïve CD4 + T cells 20–22 and abnormalities in B cell function persist. 23,24 Consequently, these children may remain susceptible to measles and need revaccination to restore protective immunity.…”