Persistent subclinical immune defects in HIV-1-infected children treated with antiretroviral therapy

Objectives: With the introduction of combined antiretroviral therapy (cART), HIV-infected children can reach adulthood with minimal clinical complications. However, long-term HIV and cART in adults are associated with immunosenescence and endorgan damage. Long-term consequences of HIV and cART in children are currently unknown. Design and method: We studied 69 HIV-infected children and adolescents under cART (0-23 years) for the occurrence of subclinical immunological aberrations in blood B and T cells, using detailed flow cytometric immunophenotyping and molecular analyses. Results: Children with undetectable plasma HIV viral loads for more than 1 year showed near-normal to normal CD4+ T-cell numbers and near-normal numbers of most class-switched memory B cells. Furthermore, expansions of aberrant CD21low B cells contracted in patients with virus suppression. In contrast, CD8+ effector T cells were increased, and CD4+ memory T cells, Vγ9+Vδ2+ T cells and CD27-IgA+ memory B cells were decreased and did not normalize under ART. Moreover, Vγ9+Vδ2+ T cells showed defects in their T-cell receptor repertoire selection. Conclusion: Our results show the effectiveness of current cART to enable the build-up of phenotypically diverse B-cell and T-cell memoryin HIV-infected children. However, several subclinical immune abnormalities were detected, which were partially caused by defective immune maturation. These persistent abnormalities were most severe in adolescents and therefore warrant long-term follow-up of HIV-infected children. Early identification of such immune defects might provide targets for monitoring future treatment optimization.