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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

Chronic neuroinflammation is associated with comorbidities in people with HIV (PWH) on antiretroviral therapy (ART). While cannabis use is associated with reduced neuroinflammation and neurocognitive impairment (NCI) in PWH, the underlying mechanisms are unknown. To address this gap in knowledge, we analyzed monocyte-derived macrophages (MDMs) from a cohort of 50 PWH and 33 people without HIV (mean age: 61.9 years), categorized by frequency of cannabis use (naïve/low, moderate, daily). We performed immunocytochemistry, RNA sequencing, and qPCR on MDMs and quantified related biomarkers in donor plasma. In this cohort study, daily cannabis use in PWH was associated with less global neurocognitive deficits, and with an anti-inflammatory immunometabolic-phenotype in MDMs characterized by (1) a metabolic shift from glycolysis to oxidative phosphorylation, (2) higher mitochondrial numbers, (3) altered cytokine profiles (pro-inflammatory downregulation, anti-inflammatory upregulation), and (4) higher brain-derived neurotrophic factor (BDNF) expression. These cellular changes were corroborated by a plasma biomarker profile in PWH including (1) lower levels of growth differentiation factor 15 and soluble triggering receptor expressed on myeloid cells 2, and (2) higher mature BDNF/precursor BDNF ratios that correlated with better cognition. Thus, cannabis use may mitigate NCI in PWH by immunometabolically reprogramming MDM function towards an anti-inflammatory and neuroprotective state. Show less

Human Immunodeficiency Virus (HIV) remains a global epidemic and is frequently associated with neurocognitive impairment, known as HIV-Associated Neurocognitive Disorder (HAND). Brain-Derived Neurotrophic Factor (BDNF), which regulates neuroplasticity, learning, and memory, may play a key role in this process. This study aimed to investigate the correlation between BDNF, CD4 levels, and cognitive function in patients with HIV. We conducted a cross-sectional study at Adam Malik General Hospital, Medan, Indonesia, from July 2024 to January 2025. Fifty-eight HIV-positive patients aged 18-60 years with CD4 ≥200 cells/mm³ and on antiretroviral therapy for at least 4 months were included. Blood samples were analyzed for serum BDNF (ELISA) and CD4 counts. Cognitive function was assessed using the Stroop Test, and correlations were examined with Spearman's test Result: Participants had a mean age of 38.77 ± 9.28 years; 79.3% were male. The mean BDNF level was 1.08 ± 0.59 ng/mL, the mean CD4 count was 512.60 ± 331.08 cells/mm³, and the mean Stroop Test score was 68.75 ± 24.60 seconds. A significant negative correlation was observed between BDNF and Stroop performance (r = -0.288, p = 0.028), indicating that higher BDNF was associated with better cognitive function. No significant correlation was found between CD4 and cognitive function (p = 0.336) Discussion: These findings suggest that reduced BDNF may contribute to cognitive impairment in HIV, whereas CD4 levels may not directly reflect neurocognitive status, particularly in patients with CD4 ≥200. BDNF levels are significantly correlated with cognitive function in HIV-positive patients, underscoring its potential role as a biomarker for HAND. 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 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