HIV感染者动脉粥样硬化发生发展规律及其炎性标志物队列研究

Cardiovascular disease (CVD), mainly atherosclerosis and atherosclerosis-associated complications, has emerged as a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in the post-antiretroviral therapy (ART) era. Compared with the general population, higher rates as well as a high prevalence of the atherosclerotic burden have been found in the HIV-infected patients. It has been suggested that in HIV-infected patients, the atherosclerotic burden is not solely attributed to the aging and ART-associated side effects. There is emerging evidence to indicate that immune activation and chronic inflammation directly or indirectly caused by HIV infection accelerate atherogenesis. This may explain why CVD risk prediction tools developed for use in the general population are inaccurate and underestimate risk in HIV-infected population. These together highlight the importance of understanding the biomarkers of inflammation and microbial translocation associated with atherosclerosis occurrence and progression and developing the atherosclerosis risk prediction tool in HIV-infected patients. Therefore, the proposed 3-year cohort study of 400 HIV-infected patients aged 18-60 years and 400 age- and gender- matched HIV-uninfected individuals, is designed to understand occurrence and progression of atherosclerosis and associated factors in HIV-infected and HIV-uninfected individuals and determine whether differences exist between two groups; and to identify biomarkers of inflammation and microbial translocation associated with atherosclerosis occurrence and progression in HIV-infected patients; and to explore and develop atherosclerosis risk prediction tool for HIV-infected population. Our findings will provide implications for atherosclerosis and atherosclerosis-associated complications prevention and treatment in HIV-infected population.

动脉粥样硬化（AS）及相关心血管疾病已逐渐成为抗病毒治疗下艾滋病病毒（HIV）感染者的主要疾病负担和死因，且发病率和患病率高于一般人群。除了老龄化以及药物副作用外，HIV感染直接或间接引起的免疫激活和慢性炎症反应可能是其主要机制。这也使得目前常用心血管疾病风险评估工具在该人群存在准确性不高和低估风险问题。因此，开展研究确定HIV感染者AS发生发展相关炎性和微生物移位标志物，探索建立适用于该人群AS风险评估工具尤其重要。为此，本项目将以18-60周岁HIV感染者和经年龄、性别匹配的HIV阴性对照各400名为研究对象，通过基线调查和其后3年随访队列研究，阐明HIV感染者和HIV阴性对照的AS发生发展规律与影响因素及其差异性，确定HIV感染者AS发生发展相关炎性和微生物移位标志物，探索建立适用于HIV感染者AS风险评估指标体系。这项研究结果对于HIV感染者AS及相关心血管疾病防治具有指导意义。

中文摘要：.动脉粥样硬化（AS）及相关心血管疾病已逐渐成为抗病毒治疗下HIV感染者的主要疾病负担和死因，且发病风险显著高于一般人群。HIV感染直接或间接引起的免疫激活和慢性炎症反应可能是其主要机制。这使得传统心血管疾病风险评估工具在该人群存在准确性不高和低估风险问题。本研究在浙江省台州市建立了HIV感染者和经年龄、性别频数匹配的HIV阴性对照的动脉粥样硬化随访队列研究。基于基线和3年随访调查，研究发现：（1）HIV感染者的传统心血管风险评分（Framingham风险评分）显著低于HIV阴性对照，但其亚临床动脉粥样硬化指标平均水平显著高于同年龄段的HIV阴性对照，且这种差异在年轻组表现更为显著；经多因素分析，这种差异在年轻组仍具统计学意义。部分年轻的HIV感染者已出现亚临床动脉粥样硬化，而这在同年龄段的HIV阴性对照中少见。（2）基于传统变量和炎症标志物，筛选建立了HIV感染者的亚临床动脉粥样硬化综合评分风险模型，包含IL-7、IL-10、D-二聚体和高血压4个变量，可以准确预测亚临床动脉粥样硬化。综合评分加年龄可准确识别亚临床动脉粥样硬化（AUC=0.833；95%CI：0.768–0.899）。按综合评分划分为低（0）、中等（1）和高风险（2–4）组。中风险组（OR=4.8，95%CI：1.7–13.7）、高风险组（OR=11.3；95%CI：3.5–36.5）的亚临床动脉粥样硬化的发生风险显著高于低风险组。（3）基于非靶向代谢组学技术，对HIV感染者动脉粥样硬化组与对照组比较分析显示，甘油磷脂代谢通路（GPL）改变最为显著，主要表现为缩醛类磷脂水平下降和GPL下游脂质介质水平升高，侧面反映了较高的炎性状态。本研究表明经过联合抗病毒治疗，HIV感染者仍然面临更高的动脉粥样硬化风险且呈年轻化趋势，与慢性炎症状态密切相关。基于炎性标志物建立的风险预测模型可准确HIV感染者预测动脉粥样硬化。