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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.
Journal of Neurovirology ( IF 3.2 ) Pub Date : 2019-07-11 , DOI: 10.1007/s13365-019-00775-6
Sara Gianella 1 , Scott L Letendre 1, 2, 3 , Jennifer Iudicello 3 , Donald Franklin 3 , Thaidra Gaufin 1 , Yonglong Zhang 4 , Magali Porrachia 1 , Milenka Vargas-Meneses 1 , Ronald J Ellis 3, 5 , Malcolm Finkelman 4 , Martin Hoenigl 1, 6
Affiliation  

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.

中文翻译:

血浆 (1 → 3)-β-D-葡聚糖和 suPAR 水平与 HIV 感染者接受抗逆转录病毒治疗的神经认知表现相关:CHARTER 分析。

尽管进行了抗逆转录病毒治疗 (ART),但 HIV 感染者 (PLWH) 的非艾滋病疾病发生率高于普通人群,例如神经认知 (NC) 损害 (NCI)。(1-3)-β-D-葡聚糖 (BDG) 是一种真菌细胞壁成分,可作为肠道屏障完整性失效以及微生物和真菌易位的生物标志物。本研究的主要目的是确定较高的 BDG 和 suPAR 血浆和脑脊液 (CSF) 水平是否与 PLWH 中的 NCI 相关。作为 2005 年至 2015 年间前瞻性 CHARTER 研究的一部分,从 61 名接受 ART(95% 病毒抑制)的男性成年 PLWH 横断面收集配对血液和 CSF 样本,这些 PLWH 接受了详细的 NC 评估。BDG 和可溶性尿激酶纤溶酶原激活物受体 (suPAR) 在冷冻血液和 CSF 样本中进行测量,而可溶性 CD14 (sCD14)、肠脂肪酸结合蛋白 (IFABP) 和 CD4/CD8 比率仅在血液中进行测量。Spearman 的 rho 相关分析评估了 BDG、其他生物标志物和 NC 性能之间的关联。血浆中 BDG 水平中位数为 18 pg/mL(范围 2-60 pg/mL)和 CSF 中 20 pg/mL(范围 0-830 pg/mL)。较高水平的血浆 BDG 与较差的 NC 性能(Spearman rho = - 0.32;p = 0.013)和存在 NCI(p = 0.027)相关。> 30 pg/mL 的血浆 BDG 截止值对 NCI 的敏感性为 30%,特异性为 100%。调整年龄后,较高的血浆 suPAR 水平也与较差的 NC 表现相关(p < 0.01)。在剩余的生物标志物和 NC 变量之间没有观察到显着的关联。BDG 的血浆水平和年龄调整的 suPAR 可能是检测 PLWH 抑制性 ART 中 NCI 的新生物标志物。
更新日期:2019-11-01
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