Brain. Robert K Heaton et al.

Modern antiretroviral therapy (ART) has increased longevity of people with HIV (PWH) and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical aging due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of antiretroviral therapy (ART) and biological aging. Here we present results of comprehensive assessments over 12 years of 402 PWH in the CNS HIV ART Effects Research (CHARTER) program, who at follow-up were composed of younger (<60 years) and older (≥60 years) subgroups. Over the 12 years, ART use and viral suppression increased in both subgroups as did systemic and psychiatric comorbidities; participants in both subgroups also evidenced neurocognitive decline beyond what is expected in typical aging. Contrary to expectations, all these adverse effects were comparable in the younger and older CHARTER subgroups, and unrelated to chronological age. Neurocognitive decline was unrelated to HIV disease or treatment characteristics but was significantly predicted by the presence of comorbid conditions, specifically diabetes, hypertension, chronic pulmonary disease, frailty, neuropathic pain, depression, and lifetime history of cannabis use disorder. These results are not consistent with premature or accelerated neurocognitive aging due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among PWH than in the general population. Good medical management of HIV disease did not prevent these adverse outcomes, and increased attention to a range of comorbid conditions in PWH may be warranted in their care.