HIV and Aging: Impacts on the Central Nervous System and Insights on Animal Models

Aging is an inevitable biological process in living species characterized by the continuous deterioration of physiological, molecular, cellular, biochemical, and functional changes. While people living with human immunodeficiency virus (HIV) infection (PLWH) are experiencing improved life expectancy due to advancements in the combinatorial antiretroviral therapy (cART) paradigms, they continue to face a higher burden of aging-associated comorbidities like diabetes, cancer, frailty, and pulmonary, liver, cardiovascular, and neurological disorders. Aging and HIV infection have been shown to have negative impacts on the form and function of the central nervous system (CNS). Whether HIV alone or cART alone or both HIV and cART acting synergistically contribute more to the aging-associated perturbations is not well studied because of limitations regarding longitudinal clinical sample availability and suitable human-aging mimicking animal models. With the current knowledge relying heavily on noninvasive approaches or postmortem specimens, gaps persist in understanding how latent HIV infection and chronic ART intake interact with the biological processes of aging in the CNS. In this article, we discussed the advantages and limitations of the models available to study aging and aim to focus on CNS-associated aging in a long-term human immune system carrying rodent model, which could not only advance the development of adjunctive therapies, when combined with cART but may also mitigate or slow the "accelerated" aging observed in older HIV-positive populations.