Transcriptomics age acceleration in prolonged treated HIV infection

Abstract

Biological aging in people with HIV (PWH) with prolonged successful antiretroviral therapy (ART) is convoluted and poorly defined. Here, we aimed to investigate the transcriptomics age estimator (TAE) in a cohort of 178 PWH on prolonged successful ART with immune reconstitution and viral suppression from the Copenhagen Comorbidity (COCOMO) cohort. We also used 143 clinical, demographical, and lifestyle factors to identify the confounders potentially responsible or associated with age acceleration. Among the PWH, 43% had an accelerated aging process (AAP), and 21% had decelerated aging process (DAP). DAP is linked with older age, European ancestry, and higher use of tenofovir disoproxil/alafenamide fumarate. A directionally class‐based gene set enrichment analysis identified the upregulation of inflammatory pathways (e.g., cytokine and Retinoic acid‐inducible gene I (RIG‐I)‐like receptor signaling pathways) and immune response like T‐cell receptor signaling, antigen processing, and presentation in AAP and the downregulation of metabolic processes like oxidative phosphorylation, pyruvate metabolism.

Oxidative phosphorylation in HIV-1 infection: impacts on cellular metabolism and immune function

“…People with HIV (PWH) face systemic metabolic challenges due to both HIV-1 and antiretroviral therapy (ART), increasing metabolic disease risks ( 37 , 38 ). Studies have shown that HIV-1 influences metabolic aging, with oxidative phosphorylation and pyruvate metabolism downregulation noted in PWH ( 39 ). Furthermore, HIV-1 affects the expression of electron transport chain (ETC) components and causes mitochondrial damage, as seen in the upregulation of Complex-IV subunit, contributing to oxidative stress ( 40 , 41 ).…”