Isnard Stéphane, Fombuena Brandon, Sadouni Manel, Lin John, Richard Corentin, Routy Bertrand, Ouyang Jing, Ramendra Rayoun, Peng Xiaorong, Zhang Yonglong, Finkelman Malcolm, Tremblay-Sher Daniel, Tremblay Cecile, Chartrand-Lefebvre Carl, Durand Madeleine, Routy Jean-Pierre
Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada.
Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.
Open Forum Infect Dis. 2021 Mar 7;8(6):ofab109. doi: 10.1093/ofid/ofab109. eCollection 2021 Jun.
Despite antiretroviral therapy (ART), people with human immunodeficiency virus (PWH) have increased risk of inflammatory comorbidities, including cardiovascular diseases. Gut epithelial damage, and translocation of bacterial lipopolysaccharide (LPS) or fungal β-d-glucan (BDG) drive inflammation in ART-treated PWH. In this study, we investigated whether markers of gut damage and microbial translocation were associated with cardiovascular risk in asymptomatic ART-treated PWH.
We cross-sectionally analyzed plasma from 93 ART-treated PWH and 52 uninfected controls older than 40 years of age from the Canadian HIV and Aging Cohort. Participants were cardiovascular disease free and underwent a cardiac computed tomography (CT) to measure total coronary atherosclerotic plaque volume (TPV). Levels of bacterial LPS and gut damage markers REG3α and I-FABP were measured by enzyme-linked immunosorbent assay. Fungal BDG levels were analyzed using the Fungitell assay.
β-d-glucan levels but not LPS were significantly elevated in ART-treated PWH with coronary artery plaque (.0007). Moreover, BDG but not LPS levels correlated with TPV (r = 0.26, .01). Intestinal fatty acid binding protein (I-FABP) but not REG3α levels correlated with TPV (r = 0.23, = .03). However, BDG and LPS levels were not elevated in uninfected controls with plaque. In multivariable models, elevated BDG levels were independently associated with the presence of coronary atherosclerosis in PWH but not in uninfected controls.
Translocation of fungal BDG was associated with coronary atherosclerosis assessed by CT-scan imaging in ART-treated PWH, suggesting a human immunodeficiency virus-specific pathway leading to cardiovascular disease. Further investigation is needed to appraise causality of this association. Translocation of fungal products may represent a therapeutic target to prevent cardiovascular disease in ART-treated PWH.Plasma levels of the fungal product β-D-Glucan, but not the bacterial product lipopolysaccharide, are associated with the presence and the size of subclinical coronary atherosclerosis plaque in people living with HIV taking antiretroviral therapy, independently of classical cardiovascular risk factors.
尽管接受了抗逆转录病毒疗法（ART），人类免疫缺陷病毒感染者（PWH）发生炎症合并症的风险仍会增加，包括心血管疾病。肠道上皮损伤以及细菌脂多糖（LPS）或真菌β-d-葡聚糖（BDG）的易位会引发接受ART治疗的PWH体内的炎症。在本研究中，我们调查了肠道损伤和微生物易位标志物是否与无症状的接受ART治疗的PWH的心血管风险相关。
我们对来自加拿大HIV与衰老队列的93名接受ART治疗的PWH和52名40岁以上未感染对照者的血浆进行了横断面分析。参与者无心血管疾病，并接受了心脏计算机断层扫描（CT）以测量冠状动脉粥样硬化斑块总体积（TPV）。通过酶联免疫吸附测定法测量细菌LPS和肠道损伤标志物REG3α及I-FABP的水平。使用Fungitell测定法分析真菌BDG水平。
在患有冠状动脉斑块的接受ART治疗的PWH中，β-d-葡聚糖水平显著升高，而LPS水平未显著升高（P = 0.0007）。此外，BDG水平而非LPS水平与TPV相关（r = 0.26，P = 0.01）。肠道脂肪酸结合蛋白（I-FABP）水平而非REG-3α水平与TPV相关（r = 0.23，P = = 0.03）。然而，在有斑块的未感染对照者中，BDG和LPS水平并未升高。在多变量模型中，BDG水平升高与PWH中冠状动脉粥样硬化的存在独立相关，但与未感染对照者无关。
在接受ART治疗的PWH中，真菌BDG的易位与通过CT扫描成像评估的冠状动脉粥样硬化相关，提示存在一条导致心血管疾病的人类免疫缺陷病毒特异性途径。需要进一步研究以评估这种关联的因果关系。真菌产物的易位可能是预防接受ART治疗的PWH发生心血管疾病的一个治疗靶点。真菌产物β-D-葡聚糖的血浆水平而非细菌产物脂多糖的血浆水平，与接受抗逆转录病毒治疗的HIV感染者亚临床冠状动脉粥样硬化斑块的存在及大小相关，且独立于经典心血管危险因素。
