Plasma suPAR and domain-specific cognitive performance in virologically suppressed women with HIV

Cognitive impairment remains common among people living with HIV despite effective antiretroviral therapy, with women disproportionately affected. Identifying stable and scalable inflammatory biomarkers that reflect domain-specific vulnerability is important for improving risk assessment in this population. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation with established analytical stability and prognostic value across multiple inflammatory conditions, including HIV. However, its relationship to cognitive performance in virologically suppressed women living with HIV (WLWH) is not well characterized. We conducted a cross-sectional study of 200 virologically suppressed WLWH enrolled at the Chicago-Cook County site of the MWCCS. Plasma suPAR was measured using the suPARnostic® AUTO Flex ELISA. Cognitive performance was assessed using demographically adjusted T-scores across executive function, psychomotor speed, motor function, memory, attention/working memory, verbal fluency, and learning. Multivariable linear regression models examined associations between log-transformed suPAR and continuous cognitive scores, adjusting for menopause status and suPAR storage duration. Relationships between log-suPAR and odds of impairment (T-score ≤ 40) were examined in adjusted logistic regression models. A same-visit subset was analyzed to account for timing differences between blood collection and cognitive testing. Higher log-suPAR was associated with lower psychomotor speed, lower motor function, and lower global average cognition. Odds of impairment in psychomotor speed, and motor function were higher with increasing log-suPAR. Sensitivity analyses showed consistent effect directions and magnitudes. These findings suggest that elevated suPAR reflects inflammation-related, domain-specific cognitive vulnerability in virologically suppressed WLWH and warrants further evaluation in longitudinal studies; clinical translation will require validation in larger, more demographically diverse cohorts, with concurrent assessment of menopausal and vascular risk profiles.