Characterization of Cellular Senescence and Exhaustion in Children Living with HIV under Antiretroviral Therapy

Abstract

Evidence has shown that chronic viral infections promote excessive and continuous immune activation, which can lead to a state of cellular exhaustion and senescence, usually associated with changes in telomere length. Chronic infection with human immunodeficiency virus (HIV), even in association with prolonged exposure to antiretroviral therapy (ART), can accelerate the process of immune senescence and favor the development of a premature aging condition in perinatally HIV-infected children. A previous study by our group demonstrated a high frequency of circulating CD4+ and CD8+ T cell populations expressing markers of cellular senescence and exhaustion in perinatally HIV-infected children (n=55), mainly in those who had ART initiated later. The present study aims to characterize the profile of cellular immunosenescence and telomeric alterations in T cells in retrospective and prospective samples derived from perinatally HIV-infected individuals, participants of the previous study cohort, who remained under follow-up (e 6 years) at HCFMUSP and Instituto Emílio Ribas. The expression profile of activation, senescence, and exhaustion markers in circulating CD4+ and CD8+ T cell populations will be evaluated using multiparameter flow cytometry technique in peripheral blood mononuclear cells (PBMC) samples obtained prospectively and compared to the results generated previously in retrospective samples from the same cohort (collected between 2016 and 2017). The PBMC samples collected at both time points (retrospective and prospective) will also be subjected to telomere length and telomerase enzyme activity analysis. The data related to cellular immunosenescence and activation will be evaluated in relation to demographic, clinical, and laboratory data (including ART follow-up, CD4+ and CD8+ T cell counts, and viral load) obtained from medical records. Considering that ART has provided an increase in the life expectancy of people living with HIV and that chronic viral infections can favor premature aging, studies on cellular immunosenescence are relevant in infections established in early childhood.