Division of Infectious Diseases & Global Public Health, University of California San Diego, San Diego, CA, USA.
Department of Medicine, University of California San Diego, San Diego, CA, USA.
J Neurovirol. 2019 Dec;25(6):837-843. doi: 10.1007/s13365-019-00775-6. Epub 2019 Jul 11.
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.
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（如神经认知障碍（NCI））发生率仍高于普通人群。(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败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 PLWH 中更高的血浆和脑脊液（CSF）BDG 和 suPAR 水平是否与 NCI 相关。2005 年至 2015 年期间，作为前瞻性 CHARTER 研究的一部分，对接受详细神经认知评估的 61 名男性成年 PLWH 进行了横断面采集，采集了他们的配对血液和 CSF 样本。冷冻血液和 CSF 样本中测量了 BDG 和可溶性尿激酶型纤溶酶原激活物受体（suPAR），而仅在血液中测量了可溶性 CD14（sCD14）、肠脂肪酸结合蛋白（IFABP）和 CD4/CD8 比值。Spearman rho 相关分析评估了 BDG 与其他生物标志物和 NC 表现之间的关联。血浆 BDG 中位数为 18pg/mL（范围 2-60pg/mL），CSF 中位数为 20pg/mL（范围 0-830pg/mL）。更高的血浆 BDG 水平与较差的 NC 表现相关（Spearman rho=-0.32;p=0.013），并且与 NCI 的存在相关（p=0.027）。血浆 BDG 截断值>30pg/mL 对 NCI 的敏感性为 30%，特异性为 100%。调整年龄后，更高的血浆 suPAR 水平也与较差的 NC 表现相关（p<0.01）。其余生物标志物与 NC 变量之间未观察到显著关联。BDG 血浆水平和年龄调整后的 suPAR 可能是检测接受抑制性 ART 的 PLWH 中 NCI 的新生物标志物。
