Randell Paul A, Jackson Akil G, Boffito Marta, Back David J, Tjia John F, Taylor Jessica, Mandalia Sundhiya, Moyle Graeme J
HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK.
Antivir Ther. 2010;15(8):1125-32. doi: 10.3851/IMP1675.
Antiretroviral therapy is associated with metabolic complications, including dyslipidaemia, body fat changes and insulin resistance. Healthy volunteer studies have demonstrated a decrease in glucose disposal associated with dosing with specific antiretrovirals.
HIV-type-1-positive male participants were randomized to receive tenofovir disoproxil fumarate and lamivudine, with either fosamprenavir (FPV)/ritonavir or lopinavir (LPV)/ritonavir twice daily. A hyperinsulinaemic euglycaemic clamp was performed at baseline and at 2 weeks after commencing treatment. The homeostasis model assessment index for insulin resistance (HOMA-IR) was also calculated at these time points. Changes in lipids and lipoprotein subfractions (by nuclear magnetic resonance spectroscopy) were assessed. A pharmacokinetic assessment was undertaken at week 2.
A total of 27 participants were enrolled. There was no significant change in whole-body insulin sensitivity or HOMA-IR from baseline or between groups. Total cholesterol increased significantly, by 6.6% with FPV and 10.9% with LPV. The changes in lipids and lipoprotein subfractions were similar between groups with increases in triglycerides, very low-density lipoprotein (VLDL) and chylomicrons, and low-density lipoprotein (LDL) particles. Although the total high-density lipoprotein (HDL) particles were not significantly altered, a decrease in small HDL particles was seen. Changes in VLDL and chylomicron particles in both groups and triglycerides and small HDL particles in the LPV group were statistically significant.
In HIV-type-1-positive men initiating antiretroviral therapy with FPV- or LPV-based regimens, there were no significant changes in whole-body insulin sensitivity after 2 weeks. A proatherogenic lipid profile characterized by increases in triglycerides, VLDL and chylomicron particles and LDL particles, and a decrease in small HDL particles, was observed in both groups.
抗逆转录病毒疗法与代谢并发症相关，包括血脂异常、体脂变化和胰岛素抵抗。健康志愿者研究表明，特定抗逆转录病毒药物给药会导致葡萄糖处置减少。
将HIV-1阳性男性参与者随机分为两组，分别每日两次接受替诺福韦酯富马酸盐和拉米夫定，同时联合福沙普那韦（FPV）/利托那韦或洛匹那韦（LPV）/利托那韦。在基线和开始治疗2周后进行高胰岛素正常血糖钳夹试验。在这些时间点还计算了胰岛素抵抗的稳态模型评估指数（HOMA-IR）。评估脂质和脂蛋白亚组分的变化（通过核磁共振波谱法）。在第2周进行药代动力学评估。
共招募了27名参与者。全身胰岛素敏感性或HOMA-IR与基线相比或两组之间均无显著变化。总胆固醇显著升高，FPV组升高6.6%，LPV组升高10.9%。两组之间脂质和脂蛋白亚组分的变化相似，甘油三酯、极低密度脂蛋白（VLDL）、乳糜微粒和低密度脂蛋白（LDL）颗粒均增加。虽然总高密度脂蛋白（HDL）颗粒没有显著改变，但小HDL颗粒减少。两组中VLDL和乳糜微粒颗粒的变化以及LPV组中甘油三酯和小HDL颗粒的变化具有统计学意义。
在开始使用基于FPV或LPV方案进行抗逆转录病毒治疗的HIV-1阳性男性中，2周后全身胰岛素敏感性无显著变化。两组均观察到以甘油三酯、VLDL、乳糜微粒颗粒和LDL颗粒增加以及小HDL颗粒减少为特征的促动脉粥样硬化血脂谱。
