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

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.