Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy

Background Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them to HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and cerebrospinal fluid (CSF) analyses. Methods Participants underwent comprehensive neuropsychological (NP) testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching (CEM) was used to reduce between-group differences in age and sex, and weighted linear/logistic regression models were used to assess the effect of HIV on outcomes. Results Data were analyzed from 155 PWH on ART for at least 15 years and 100 HIV-negative controls. Compared to controls, PWH scored lower in the domains of attention/working memory (PWH Least Square Mean [LSM]=50.4 vs. controls LSM=53.1, p=0.008) and motor function (44.6 vs. 47.7, p=0.009), and a test of information processing speed (symbol search 30.3 vs. 32.2, p=0.003). They were more likely to self-report a higher number of cognitive difficulties in everyday life (p=0.011). PWH also reported more depressive symptoms, general anxiety, and use of psychiatric medications (all with p