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

TitlePlasma (1 → 3)-β-D-glucan and suPAR levels correlate with neurocognitive performance in people living with HIV on antiretroviral therapy: a CHARTER analysis.
Publication TypeJournal Article
Year of Publication2019
AuthorsGianella, S, Letendre, SL, Iudicello, J, Franklin, D, Gaufin, T, Zhang, Y, Porrachia, M, Vargas-Meneses, M, Ellis, RJ, Finkelman, M, Hoenigl, M
JournalJ Neurovirol
Volume25
Issue6
Pagination837-843
Date Published2019 12
ISSN1538-2443
KeywordsAdult, Anti-Retroviral Agents, beta-Glucans, Biomarkers, Cognitive Dysfunction, Cross-Sectional Studies, Female, HIV Infections, Humans, Male, Middle Aged, Receptors, Urokinase Plasminogen Activator
Abstract

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)-β-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 and suPAR were associated with NCI in PLWH. 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 and 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. 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 the presence of NCI (p = 0.027). A plasma BDG cutoff of > 30 pg/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 < 0.01). No significant associations were observed between the remaining biomarkers and the NC variables. Plasma levels of BDG and age-adjusted suPAR may be new biomarkers for the detection of NCI in PLWH on suppressive ART.

DOI10.1007/s13365-019-00775-6
Alternate JournalJ Neurovirol
PubMed ID31297727
PubMed Central IDPMC6923595
Grant ListK24 MH097673 / MH / NIMH NIH HHS / United States
P50 DA026306 / DA / NIDA NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
R25 MH081482 / MH / NIMH NIH HHS / United States
R21 HD094646 / HD / NICHD NIH HHS / United States
R21 AI134295 / AI / NIAID NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States
R21 MH113477 / MH / NIMH NIH HHS / United States
R24 AI106039 / AI / NIAID NIH HHS / United States