Neuropathologic findings in a community-based autopsy cohort of older, virally suppressed, people with HIV

Combination antiretroviral therapy (cART) has reduced the incidence of HIV-related mortality, leading to a growing population of older virally suppressed people with HIV (PWH). cART has also decreased the prevalence of HIV-associated dementia; however, many virally suppressed PWH still experience milder forms of cognitive impairment. It remains unclear whether aging virally suppressed PWH demonstrate distinct risks or patterns of neurodegenerative pathology. We examined brain tissue of 13 virally suppressed PWH and 13 matched HIV-negative controls from a community-based cohort and characterized β-amyloid (Aβ), tau, α-synuclein, and TDP-43 pathology. Both groups had similar demographics, medical comorbidities, and routine histologic brain findings. PWH demonstrated trends toward an increased prevalence of both Alzheimer disease (AD) and non-AD neurodegenerative pathologies, including Aβ pathology, higher stage tau pathology, aging-related tau astrogliopathy, and α-synuclein pathology. They showed similar trends toward increased severity of Aβ and tau pathology. We also identified a negative correlation between the burden of entorhinal cortical neurofibrillary tangles and end-of-life body mass index in PWH. Thus, PWH may have a greater burden of neurodegenerative pathology, including both AD and non-AD neurodegenerative pathologies; there is a need for the assessment of neurodegenerative pathology in community-based cohort studies to understand mechanisms of HIV-associated neuropathology and cognitive impairment in aging virally suppressed PWH.