The Impact of HIV on Early Brain Aging-A Pathophysiological (Re)View

Background/Objectives: This review aims to provide a comprehensive understanding of how HIV alters normal aging trajectories in the brain, presenting the HIV-related molecular mechanisms and pathophysiological pathways involved in brain aging. The review explores the roles of inflammation, oxidative stress, and viral persistence in the brain, highlighting how these factors contribute to neuronal damage and cognitive impairment and accelerate normal brain aging. Additionally, it also addresses the impact of antiretroviral therapy on brain aging and the biological markers associated with its occurrence. Methods: We extensively searched PubMed for English-language articles published from 2000 to 2024. The following keywords were used in the search: "HIV", "brain", "brain aging", "neuroinflammation", "HAART", and "HAND". This strategy yielded 250 articles for inclusion in our review. Results: A combination of blood-brain barrier dysfunction, with the direct effects of HIV on the central nervous system, chronic neuroinflammation, telomere shortening, neurogenesis impairments, and neurotoxicity associated with antiretroviral treatment (ART), alters and amplifies the mechanisms of normal brain aging. Conclusions: Current evidence suggests that HIV infection accelerates neurodegenerative processes of normal brain aging, leading to cognitive decline and structural brain changes at an earlier age than typically observed in the general population.