AIDS. 2026 May 4. doi: 10.1097/QAD.0000000000004534. Online ahead of print.
ABSTRACT
OBJECTIVE: Despite suppressive antiretroviral therapy (ART), people with HIV (PWH) frequently experience neurocognitive impairment, yet underlying mechanisms remain elusive. We hereby evaluated biomarkers of brain injury, inflammation and gut barrier dysfunction to identify factors associated with cognitive performance in PWH.
DESIGN: PWH on suppressive ART and people without HIV (PWoH) were cross-sectionally enrolled.
METHODS: PWH underwent a comprehensive neurocognitive assessment and HIV-associated neurocognitive disorder (HAND) was diagnosed. We measured plasma markers of neuroaxonal damage and astroglial activation (NF-L/GFAP by Simoa), inflammation/monocyte activation (IP-10/IL-6/sCD14 by ELISA), gut barrier disruption (I-FABP/E-cadherin/zonulin by ELISA) and microbial translocation (LBP/EndoCAb IgG by ELISA). Non-parametric tests and multivariable regression were used for analyses.
RESULTS: Forty PWH [17 HAND+ (asymptomatic neurocognitive impairment), 23 HAND-] and 10 PWoH were included. Compared to PWoH, PWH had higher levels of inflammation/monocyte activation (IP-10/sCD14), gut barrier disruption (I-FABP) and microbial translocation (LBP/EndoCAb-IgG). PWH HAND+ showed higher levels of GFAP/IL-6/sCD14 compared to PWH HAND-. At logistic regression adjusting for age, sex and CD4 T-cell nadir, HAND confirmed associated with higher GFAP/sCD14. More specifically, at linear regression adjusting for the same variables, higher GFAP levels were associated with lower global cognitive performance, worse attention and working memory, speed of information processing, motor skills, as well as learning and memory; higher IL-6 with worse abstraction and executive functions; higher IL-6 and sCD14 with worse verbal fluency.
CONCLUSIONS: In our cohort of ART-suppressed PWH, asymptomatic neurocognitive impairment was associated with markers of astrocyte/monocyte activation and inflammation rather than with markers of neuroaxonal damage, gut barrier disruption, or microbial translocation.
PMID:42084015 | DOI:10.1097/QAD.0000000000004534