Epigenetic aging is a hallmark of HIV pathogenesis and phenotypic outcomes

First-generation epigenetic clocks indicate an average of 5–7 years of age acceleration in people with HIV compared to those without.

• Epigenetic aging is associated with cellular aging processes, including cellular senescence and changes in metabolism.
• Human endogenous retroviruses and transposable elements are linked to aging mechanisms in people with HIV.
• Second-generation epigenetic clocks predict increased morbidity and mortality related to accelerated aging in this population.
• Third-generation epigenetic clocks reveal insights into aging mechanisms like DNA damage and adaptations across different organ systems.
• Sex-based differences in aging patterns are observed among people with HIV.

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