HIV disease, metabolic dysfunction and atherosclerosis: A three year prospective study

HIV infection is known to be associated with cardiometabolic abnormalities; here we investigated the progression and causes of these abnormalities. Three groups of participants were recruited: HIV-negative subjects and two groups of treatment-naïve HIV-positive subjects, one group initiating antiretroviral treatment, the other remaining untreated. Intima-media thickness (cIMT) increased in HIV-positive untreated group compared to HIV-negative group, but treatment mitigated the difference. We found no increase in diabetes-related metabolic markers or in the level of inflammation in any of the groups. Total cholesterol, low density lipoprotein cholesterol and apoB levels were lower in HIV-positive groups, while triglyceride and Lp(a) levels did not differ between the groups. We found a statistically significant negative association between viral load and plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, apoA-I and apoB. HIV-positive patients had hypoalphalipoproteinemia at baseline, and we found a redistribution of sub-populations of high density lipoprotein (HDL) particles with increased proportion of smaller HDL in HIV-positive untreated patients, which may result from increased levels of plasma cholesteryl ester transfer protein in this group. HDL functionality declined in the HIV-negative and HIV-positive untreated groups, but not in HIV-positive treated group. We also found differences between HIV-positive and negative groups in plasma abundance of several microRNAs involved in lipid metabolism. Our data support a hypothesis that cardiometabolic abnormalities in HIV infection are caused by HIV and that antiretroviral treatment itself does not influence key cardiometabolic parameters, but mitigates those affected by HIV.

人类免疫缺陷病毒（HIV）感染已知与心血管代谢异常相关；本研究旨在探究此类异常的进展及其诱因。本研究共招募三组受试者：HIV阴性者，以及两组初治HIV阳性者——其中一组启动抗反转录病毒治疗（antiretroviral treatment），另一组未接受任何治疗。与HIV阴性组相比，未接受治疗的HIV阳性组的内膜中层厚度（cIMT）显著升高，但抗反转录病毒治疗可缓解这一差异。各组的糖尿病相关代谢标志物水平及炎症水平均未出现升高。HIV阳性组的总胆固醇、低密度脂蛋白胆固醇及载脂蛋白B（apoB）水平均低于HIV阴性组，而甘油三酯与脂蛋白(a)（Lp(a)）水平在各组间无显著差异。本研究发现病毒载量与血浆总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇（HDL cholesterol）、载脂蛋白A-I（apoA-I）及载脂蛋白B（apoB）水平呈统计学显著负相关。HIV阳性患者基线时存在低α脂蛋白血症；本研究还观察到，未接受治疗的HIV阳性患者的高密度脂蛋白（HDL）颗粒亚群发生重塑，其中小型HDL颗粒的占比升高，这可能与该组患者的血浆胆固醇酯转移蛋白（cholesteryl ester transfer protein）水平升高有关。HIV阴性组与未接受治疗的HIV阳性组的高密度脂蛋白功能均出现下降，但接受抗反转录病毒治疗的HIV阳性组未出现此类变化。本研究还观察到，HIV阳性组与阴性组的血浆中多种参与脂质代谢的微小RNA（microRNAs）的丰度存在差异。本研究数据支持如下假说：HIV感染相关的心血管代谢异常由HIV本身所致，而抗反转录病毒治疗本身并不会影响关键心血管代谢参数，但可缓解HIV引发的此类异常。