Hospital Universitari Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
Hospital Universitari Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain; Metabolomics Platform, Department of Electronic Engineering, Universitat Rovira i Virgili, IISPV, Tarragona, Spain.
Atherosclerosis. 2018 Jun;273:28-36. doi: 10.1016/j.atherosclerosis.2018.04.008. Epub 2018 Apr 9.
Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes.
To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months. Univariate and multivariate analyses were performed to evaluate the predictive power of NMR spectroscopy.
VLDL-metabolism (including VLDL lipid concentrations, sizes, and particle numbers), total triglycerides and lactate levels resulted in good classifiers of dyslipidemia (AUC 0.903). Total particles/HDL-P ratio was significantly higher in ART-associated dyslipidemia compared to ART-normolipidemia (p = 0.001). Large VLDL-Ps were positively associated with both LDL-triglycerides (ρ 0.682, p < 0.001) and lactate concentrations (ρ 0.416, p < 0.001), the last one a marker of mitochondrial low oxidative capacity.
Our data suggest that circulating metabolites have better predictive values for HIV/ART-related dyslipidemia onset than do the biochemical markers associated with conventional lipid measurements. NMR identifies changes in VLDL-P, lactate and LDL-TG as potential clinical markers of baseline HIV-dyslipidemia predisposition. Differences in circulating metabolomics, especially differences in particle size, are indicators of important derangements of mitochondrial function that are linked to ART-related dyslipidemia.
HIV 感染者的血脂异常具有独特性，且从病理生理学角度看与宿主因素、HIV 本身以及抗逆转录病毒治疗（ART）有关。核磁共振光谱（NMR）的应用除了提供常规血脂测量的脂蛋白亚类和颗粒大小数据外，还提供了更多数据。
为了研究脂蛋白谱的能力，我们在一个 103 名初治、未使用非核苷类逆转录酶抑制剂（NNRTI）的 HIV 感染者队列中使用循环代谢组学方法进行了研究，这些患者开始接受 NNRTI 为基础的 ART，随后对这些患者进行了 36 个月的随访。采用单变量和多变量分析评估 NMR 光谱的预测能力。
VLDL 代谢（包括 VLDL 脂质浓度、大小和颗粒数量）、总甘油三酯和乳酸水平是血脂异常的良好分类器（AUC 0.903）。与 ART 正常血脂组相比，ART 相关血脂异常患者的总颗粒/HDL-P 比值明显升高（p=0.001）。大 VLDL-P 与 LDL 甘油三酯（ρ0.682，p<0.001）和乳酸浓度（ρ0.416，p<0.001）呈正相关，后者是线粒体低氧化能力的标志物。
我们的数据表明，与常规血脂测量相关的生化标志物相比，循环代谢物对 HIV/ART 相关血脂异常的发生具有更好的预测价值。NMR 可识别 VLDL-P、乳酸和 LDL-TG 的变化，这些变化可能是 HIV 血脂异常易感性的潜在临床标志物。循环代谢组学的差异，特别是颗粒大小的差异，是与 ART 相关血脂异常相关的线粒体功能重要紊乱的指标。
