UC San Diego

The advent of effective antiretroviral medications (ARVs) has led to an aging of the HIV population with approximately 50% of people with HIV (PWH) being over the age of 50 years. Neurocognitive complications, typically known as HIV-associated neurocognitive disorders (HAND), persist in the era of ARVs and, in addition to risk of HAND, older PWH are also at risk for age-associated, neurodegenerative disorders including Alzheimer's disease (AD). It has been postulated that risk for AD may be greater among PWH due to potential compounding effects of HIV and aging on mechanisms of neural insult. We are now faced with the challenge of disentangling AD from HAND, which has important prognostic and treatment implications given the more rapidly debilitating trajectory of AD. Herein, we review the evidence to date demonstrating both parallels and differences in the profiles of HAND and AD. We specifically address similarities and difference of AD and HAND as it relates to (1) neuropsychological profiles (cross-sectional/longitudinal), (2) AD-associated neuropathological features as evidenced from neuropathological, cerebrospinal fluid and neuroimaging assessments, (3) biological mechanisms underlying cortical amyloid deposition, (4) parallels in mechanisms of neural insult, and (5) common risk factors. Our current understanding of the similarities and dissimilarities of AD and HAND should be further delineated and leveraged in the development of differential diagnostic methods that will allow for the early identification of AD and more suitable and effective treatment interventions among graying PWH.