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

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.

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Funding

This work was supported by funds from the following: HNRP developmental grant PST-HN68 (from parent NIMH grant MH062512), and grants from the National Institutes of Health: AI036214, DA026306, AI064086, MH081482, MH113477, K24 MH097673 and AI106039. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript N01MH022005, HHSN271201000036C, R01MH107345 K23DA037793 R01 DA 034362.

Author information

Correspondence to Sara Gianella or Martin Hoenigl.

Ethics declarations

The UCSD Human Research Protections Program approved the study protocol, consent, and all study-related procedures. All study participants provided voluntary, written informed consent before any study procedures were undertaken.

Conflict of interest

MH received grant funding from Gilead. YZ and MF are employees of Associates of Cape Cod. All other authors declare no conflict of interest.

Off-label use

Fungitell®, the FDA-cleared IVD kit used for the measurement of (1 → 3)-β-glucan in serum, does not have an indication for the diagnostic use of BG titers in CSF. The data presented here represents the research use only.

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Gianella, S., Letendre, S.L., Iudicello, J. et al. Plasma (1 → 3)-β-d-glucan and suPAR levels correlate with neurocognitive performance in people living with HIV on antiretroviral therapy: a CHARTER analysis. J. Neurovirol. 25, 837–843 (2019). https://doi.org/10.1007/s13365-019-00775-6

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Keywords

  • CSF
  • Plasma
  • Neurocognitive impairment
  • Microbial translocation
  • Virally suppressed
  • Non-AIDS events
  • suPAR
  • sCD14
  • IFABP
  • BDG