Changes in Cellular Senescence Biomarkers Across Individuals at Different Stages of HIV Infection Before and After a Year on Antiretroviral Therapy.

Abstract

People with HIV (PWH) experience chronic inflammation and more age-related comorbidities despite antiretroviral therapy (ART). Classical senescence biomarkers (e.g., SA-βGal, p16INK4a, γH2AX and Bcl-2) and senescence-associated secretory phenotype (SASP) factors such as IL-6 reflect cellular senescence. This study assesses those markers in a male cohort of PWH across infection stages, pre/post-ART. We analyzed blood samples from 39 PWH at primary, chronic and advanced HIV infection, before and after one year on ART, and 13 age- and sex-matched HIV-negative controls. Classical cellular senescence biomarkers in T-cells and monocytes, along with plasma SASP factors and immune checkpoints, were assessed via flow cytometry and Luminex. PWH exhibited elevated cellular senescence, SASP and immune checkpoint markers (such as SA-βGal, p16INK4a, γH2AX, Bcl-2, CD87, IL-6, IL-10, TNF-RI/RII, CD30, IL-8, RANTES, CXCL1, PD-1, PD-L1, PD-L2, LAG-3, CTLA-4 and TIM-3) particularly in chronic and advanced stages, which generally persisted after ART, but not in PWH treated in primary HIV infection. Senescence biomarkers in T-cells and SASP components in plasma positively correlated with immunosenescence, T-cell activation, HIV p24 expression and negatively correlated with CD4 count and CD4/CD8 ratio. HIV infection promotes persistent cellular senescence despite ART in advanced and chronic infection. Thus, future senolytic or senomorphic strategies against cellular senescence may reduce chronic inflammation and aging-related complications in PWH.