Conclusion
Increased CSF extracellular vesicles correlate with neuronal injury biomarker NFL in cART-treated HIV-positive individuals with neurocognitive impairment, suggesting potential applications as novel biomarkers of CNS injury.
Methods
NFL, S100B and neopterin were measured by ELISA in 190 CSF samples from 112 individuals (67 HIV-positive and 45 HIV-negative). CSF extracellular vesicles were isolated and characterized by electron microscopy, nanoparticle tracking analysis, immunoblotting for exosome markers (CD9, CD63, CD81, FLOT-1) and ELISA for HLA-DR.
Objective
The relationship of cerebrospinal fluid (CSF) extracellular vesicles to neurocognitive impairment (NCI) in HIV-infected individuals is unclear. Here, we characterize CSF extracellular vesicles and their association with central nervous system (CNS) injury related biomarkers [neurofilament light (NFL), S100B, neopterin] and NCI in HIV-positive individuals on combination antiretroviral therapy (cART). Design: A cross-sectional and longitudinal study of CSF samples from HIV-positive individuals on cART.
Results
HIV-positive individuals had median age 52 years, 67% with suppressed plasma viral load (< 50 copies/ml), median CD4 nadir 66 cells/μl and CD4 cell count 313 cells/μl. CSF NFL, S100B and neopterin levels were higher in HIV-positive vs. HIV-negative individuals, and nonsuppressed vs. suppressed HIV-positive individuals. Although CSF NFL and S100B levels were higher in NCI vs. unimpaired HIV-positive individuals (P < 0.05), only NFL was associated with NCI in adjusted models (P < 0.05). CSF extracellular vesicles were increased in HIV-positive vs. HIV-negative individuals, and NCI vs. unimpaired HIV-positive individuals (P < 0.05), and correlated positively with NFL (P < 0.001). HLA-DR was enriched in CSF extracellular vesicles from HIV-positive individuals with NCI (P < 0.05), suggesting that myeloid cells are a potential source of CSF extracellular vesicles during HIV infection.