HIV-1 low-level viremia affects T cell activation rather than T cell development in school-age children, adolescents, and young adults during antiretroviral therapy

Abstract

Objectives: Given the improvements in antiretroviral therapy (ART) in recent years, more pediatric HIV patients receiving ART are reaching adolescence and adulthood. This study investigated the influence of poor virological response (low-level viremia (LLV) and virological failure (VF)) on the immune system of these patients.

Methods: HIV-infected, ART-experienced pediatric patients (n=206) were enrolled in this cross-sectional study. The patients were subdivided into school-age children/early adolescents, middle adolescents, and late adolescents/young adults according to their age, and further classified into virological suppression (VS), LLV, and VF groups according to plasma viral load (pVL) measurement. Thymic output, T cells subsets, and immune activation were analyzed by flow cytometry.

Results: Compared with VS patients, VF patients displayed decreased CD4⁺ T cell counts, while LLV and VS patients had comparable CD4⁺ T cell counts regardless of age. Compared with VS patients, LLV and VF patients had higher percentages of CD8⁺HLA-DR⁺ and CD8⁺CD38^high T cells, and the immune activation was positively correlated with pVL in VF and LLV patients. Thymic output levels (CD31⁺) and regulatory T cell subpopulations in LLV and VF patients were comparable to those in VS patients. LLV patients showed comparable percentages of T cell subsets (T_N, T_CM, T_EMRA, and T_EM) as VS patients in all age groups.

Conclusions: LLV causes excessive immune activation although it does not impair T cell recovery or naïve-to-memory T cell conversion in pediatric patients living with HIV. Therefore, T cell immune activation should be monitored at the management of LLV during ART.

Keywords: Antiretroviral therapy; Immune activation; Low-level viremia (LLV); Pediatric HIV/AIDS; Thymic output.