We investigated the relationship between cerebrospinal fluid (CSF) and plasma biomarkers of inflammation, neurodegeneration, and neurocognitive performance in people with HIV (PWH), using longitudinal Show more
We investigated the relationship between cerebrospinal fluid (CSF) and plasma biomarkers of inflammation, neurodegeneration, and neurocognitive performance in people with HIV (PWH), using longitudinal samples from two previously published cohorts: ACTG A5090 (virally suppressed on antiretroviral therapy, ART) and A736 (ART-naïve or failing). We analyzed paired CSF and plasma samples, as well as 7-domain standardized neurocognitive test scores, at baseline and 24 weeks. Biomarkers included markers of inflammation (e.g., TNF-α, IL-6, IP-10) and neurodegeneration (e.g., NFL, p-Tau217, Aβ42), which were quantified via high-sensitivity immunoassays. Associations with cognition were tested using regression, mediation, and interaction models. Cross-sectional analyses revealed nominal associations between inflammatory markers and cognitive performance, with plasma IL-6 and IP-10 at baseline, and CSF TNFα at week 24 showing the strongest correlations (p < 0.05, uncorrected); however, none survived correction for multiple comparisons. Conversely, higher CSF Aβ42 and plasma BDNF were positively associated with memory and executive function. Longitudinally, biomarker changes did not significantly predict change in global cognition (ΔNPZ-8); the strongest trend (p-Tau217, ρ = -0.12, p = 0.38) was not statistically significant, and multivariate models failed to identify robust predictors (R These results suggest a potential role of CSF TNFα in mediating the neurocognitive effects of HIV and highlight compartment-specific inflammatory dynamics. Plasma TNFα, GFAP, and NFL may serve as peripheral indicators of CNS pathology, though with only moderate concordance. Astrocyte-tau interactions require cautious interpretation pending replication in larger cohorts. Show less
People with HIV (PWH) have a higher risk of central nervous system (CNS) diseases and a timely differential diagnosis may be essential for patient management. Cerebrospinal fluid (CSF) biomarkers have Show more
People with HIV (PWH) have a higher risk of central nervous system (CNS) diseases and a timely differential diagnosis may be essential for patient management. Cerebrospinal fluid (CSF) biomarkers have proven effective in diagnosing neuronal and astrocyte involvement in neurological disorders, but the invasiveness of this method makes it difficult to obtain results; thus, easy-to-obtain matrices (e.g., plasma) have to be analysed. Consequently, the aim of this study was to quantify biomarkers in both serum and CSF with different kits, correlating levels obtained in the two matrices and understanding their impact on blood brain barrier (BBB) permeability. CSF and serum from PWH were analysed through Single Molecule Array (Simoa SR-X, Quanterix). We measured markers of neuronal damage (NfL, tau, ptau), β-amyloid peptides (Aβ Show less