Serum but not cerebrospinal fluid biomarkers are associated with domain-specific cognitive performance in PWH

Blood biomarkers would be the ideal tool in routine practice in early identifying People With HIV (PWH) with low cognitive performance (LNP). We aimed to assess the diagnostic performance of neurodegeneration and brain injury biomarkers in cerebrospinal fluid (CSF) and serum to detect global and domain-specific cognitive performance in PWH. Retrospective cross-sectional study. Serum and CSF Tau, NFL, GFAP, UCH-L1, BDNF, AB40 and AB42, and CSF SNAP25 concentrations were measured by Single Molecule Assay (SiMoA) in treated PWH without neurological confounders. Global Deficit Score (GDS) was calculated assessing 6 cognitive domains; LNP defined as GDS ≥ 0.5. Correlations, AUROC, and diagnostic accuracy metrics were used to study the relationships between GDS, domain impairment, and biomarkers. 74 adult PWH on suppressive antiretroviral therapy were included (53% male, age 56 ± 9.8 years, median CD4 + T-cells 542/µL); 50% had LNP. Despite moderate-to-strong correlations between CSF and serum biomarkers, only serum GFAP was associated with LNP (AUROC 0.67, p = 0.007, sensitivity 67.6%, specificity 64.9%). Serum Tau was associated with impairment in memory (AUROC 0.66, p = 0.031, sensitivity 85.0%, specificity 42.9%), processing speed (AUROC 0.71, p = 0.002, sensitivity 46.0%, specificity 99.5%), and motor functions (AUROC 0.74, p < 0.001, sensitivity 55.6% specificity 88.5%); serum NFL with executive dysfunction (AUROC 0.66, p = 0.024, sensitivity 80.8%, specificity 50.0%). Variably combining serum GFAP, Tau, and NFL did not improve accuracy in detecting LNP. We observed very selective relationships between specific serum biomarkers and cognitive phenotypes, suggesting heterogeneity of the mechanisms underlying LNP in PWH, which may limit the diagnostic power of biomarker-based strategies.