Grupo de Virología Clínica, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complejo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidad de A Coruña (UDC), A Coruña, Spain.
Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Complejo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain.
Sci Rep. 2019 Nov 20;9(1):17184. doi: 10.1038/s41598-019-53761-7.
Cardiovascular disease is an important cause of morbidity and mortality in people living with HIV (PLWH), who commonly experience lipid disturbances. The aim of this study was to determine whether the plasma lipidomic profile differs between PLWH receiving a darunavir-based ART and those receiving integrase inhibitor-based ART. This was a cross-sectional study of unselected patients for whom metabolomic analysis was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry. Data for the two subgroups were compared by calculating the log2 of the fold change for each metabolite and then grouping these into the main lipid families. Sixty-two PLWH aged 49.3 ± 8.6 years (82% men) were included: 12 patients (19.4%) had hypertension, 8 (12.9%) had type 2 diabetes, 25 (41.0%) had dyslipidaemia and 9 (14.5%) were taking statins, without significant differences in all these variables between the two groups. Twenty-five (40.3%) received darunavir-based ART and 37 (59.7%) integrase inhibitor-based ART. Although the differences were not statistically significant, patients treated with darunavir-based ART had higher concentrations of total cholesterol (211 mg/dL vs 194 mg/dL), LDL-cholesterol (132 mg/dL vs 117 mg/dL) and triglycerides (155 mg/dL vs 122 mg/dL), and lower HDL-cholesterol concentration (50 mg/dL vs 52 mg/dL). The main lipid families and metabolites differed slightly between groups (log2-fold change; P-value): ceramides (-0.07; 0.49), phosphatidylinositols (-0.05; 0.63), diacylglycerols (0.10; 0.64), phosphatidylethanolamines (0.03; 0.78), triacylglycerols (0.27; 0.18) and lysophosphatidylethanolamines (0.03; 0.83). In the integrase inhibitor-based group, the use of tenofovir alafenamide fumarate significantly increases the majority of lipid fractions, when compared with tenofovir disoproxil fumarate. The lipidomic profile did not differ between PLWH treated with darunavir-based or integrase inhibitor-based ART. This was especially true for ceramides, which are involved in cardiovascular disease. Further studies are needed to study the impact of ART in lipidomic profile.
心血管疾病是 HIV 感染者（PLWH）发病率和死亡率的重要原因，他们通常会出现脂质紊乱。本研究旨在确定接受达芦那韦为基础的 ART 和接受整合酶抑制剂为基础的 ART 的 PLWH 的血浆脂质组谱是否存在差异。这是一项对未选择患者进行的横断面研究，对其进行代谢组学分析时使用超高效液相色谱-质谱联用。通过计算每个代谢物的对数 2 倍变化的倍数，并将这些变化分组到主要脂质家族中，比较两组患者的数据。纳入 62 名年龄为 49.3±8.6 岁（82%为男性）的 PLWH：12 名患者（19.4%）患有高血压，8 名（12.9%）患有 2 型糖尿病，25 名（41.0%）患有血脂异常，9 名（14.5%）正在服用他汀类药物，但两组之间在所有这些变量上均无显著差异。25 名患者（40.3%）接受达芦那韦为基础的 ART，37 名患者（59.7%）接受整合酶抑制剂为基础的 ART。尽管差异无统计学意义，但接受达芦那韦为基础的 ART 治疗的患者总胆固醇（211mg/dL 比 194mg/dL）、LDL-胆固醇（132mg/dL 比 117mg/dL）和甘油三酯（155mg/dL 比 122mg/dL）浓度较高，而 HDL-胆固醇浓度较低（50mg/dL 比 52mg/dL）。两组间主要脂质家族和代谢物略有差异（对数 2 倍变化；P 值）：神经酰胺（-0.07；0.49）、磷脂酰肌醇（-0.05；0.63）、二酰基甘油（0.10；0.64）、磷脂酰乙醇胺（0.03；0.78）、三酰基甘油（0.27；0.18）和溶血磷脂酰乙醇胺（0.03；0.83）。在整合酶抑制剂为基础的组中，与富马酸替诺福韦二吡呋酯相比，使用富马酸丙酚替诺福韦艾拉酚胺显著增加了大多数脂质分数。接受达芦那韦为基础或整合酶抑制剂为基础的 ART 治疗的 PLWH 的脂质组谱没有差异。这在涉及心血管疾病的神经酰胺中尤其如此。需要进一步研究来研究 ART 在脂质组谱中的影响。
