Plasma (1 → 3)-β-d-glucan and suPAR levels correlate with neurocognitive performance in people living with HIV on antiretroviral therapy: a CHARTER analysis

BACKGROUND: Despite antiretroviral therapy (ART), people living with HIV (PLWH) have higher rates of non-AIDS disorders, such as neurocognitive (NC) impairment (NCI) than the general population. (1–3)-b-D-glucan (BDG) is a fungal cell wall component which serves as a biomarker for gut barrier integrity failure and microbial and fungal translocation. The primary objective of this study was to determine whether higher plasma and cerebrospinal fluid (CSF) levels of BDG were associated with NCI in PLWH. METHODS: Paired blood and CSF samples were collected cross-sectionally from 61 male adult PLWH on ART (95% virally suppressed) who underwent a detailed NC assessment as part of the prospective CHARTER study between 2005–2015. BDG and soluble urokinase plasminogen activator receptor (suPAR) were measured in frozen blood and CSF samples while soluble CD14 (sCD14), intestinal fatty acid binding protein (IFABP) and CD4/CD8 ratio were measured in blood only. Spearman’s rho correlation analysis assessed associations between BDG, other biomarkers and NC performance. RESULTS: Median BDG levels were 18 pg/mL in plasma (range: 2–60 pg/mL) and 20 pg/mL in CSF (range: 0–830 pg/mL). Higher levels of plasma BDG were associated with worse NC performance (Spearman’s rho=−0.32; p=0.013) and with presence of NCI (p=0.027). A plasma BDG cut-off of >30pg/mL was 30% sensitive and 100% specific for NCI. After adjusting for age, higher plasma SuPAR levels were also associated with worse NC performance (p