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. 2019 Dec;25(6):837-843.
doi: 10.1007/s13365-019-00775-6. Epub 2019 Jul 11.

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

Sara Gianella  1 , Scott L Letendre  2   3   4 , Jennifer Iudicello  4 , Donald Franklin  4 , Thaidra Gaufin  2 , Yonglong Zhang  5 , Magali Porrachia  2 , Milenka Vargas-Meneses  2 , Ronald J Ellis  4   6 , Malcolm Finkelman  5 , Martin Hoenigl  2   7
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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

Sara Gianella et al. J Neurovirol. 2019 Dec.

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.

Keywords: BDG; CSF; IFABP; Microbial translocation; Neurocognitive impairment; Non-AIDS events; Plasma; Virally suppressed; sCD14; suPAR.

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Conflict of interest statement

Conflicts of interest

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

Figures

Figure 1:
Figure 1:
Scatterplots of correlation of plasma beta-D-glucan levels with Global Deficit Scores.
Figure 2:
Figure 2:
Plasma and CSF beta-D-glucan levels in those with neurocognitive impairment (i.e., Global Deficit Scores>0.5) versus those without neurocognitive impairment.
See this image and copyright information in PMC

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