Flammer A J, Vo N T T, Ledergerber B, Hermann F, Gämperli A, Huttner A, Evison J, Baumgartner I, Cavassini M, Hayoz D, Quitzau K, Hersberger M, Sudano I, Ruschitzka F, Lüscher T F, Noll G, Weber R
Cardiovascular Centre, Cardiology, University Hospital Zurich, Zurich, Switzerland.
Heart. 2009 Mar;95(5):385-90. doi: 10.1136/hrt.2007.137646. Epub 2008 Jul 24.
Impaired endothelial function was demonstrated in HIV-infected persons on protease inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. This study determined whether endothelial function improves after switching from other PI to atazanavir.
Randomised, observer-blind, treatment-controlled trial.
Three university-based outpatient clinics.
39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting low-density lipoprotein (LDL)-cholesterol greater than 3 mmol/l.
Patients were randomly assigned to continue the current PI or change to unboosted atazanavir.
Endpoints at week 24 were endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery, lipid profiles and serum inflammation and oxidative stress parameters.
Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9% (SD 1.8) on atazanavir versus 4.0% (SD 1.5) in controls). After 24 weeks' treatment, FMD decreased to 3.3% (SD 1.4) and 3.4% (SD 1.7), respectively (all p = ns). Total cholesterol improved in both groups (p<0.0001 and p = 0.01, respectively) but changes were more pronounced on atazanavir (p = 0.05, changes between groups). High-density lipoprotein and triglyceride levels improved on atazanavir (p = 0.03 and p = 0.003, respectively) but not in controls. Serum inflammatory and oxidative stress parameters did not change; oxidised LDL improved significantly in the atazanavir group.
The switch from another PI to atazanavir in treatment-experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Atherogenic lipid profiles and direct effects of antiretroviral drugs on the endothelium may affect vascular function.
NCT00447070.
接受含蛋白酶抑制剂（PI）的抗逆转录病毒治疗的HIV感染者存在内皮功能受损，这可能是由于脂质代谢改变所致。阿扎那韦是一种引起致动脉粥样硬化脂蛋白变化较小的PI。本研究旨在确定从其他PI转换为阿扎那韦后内皮功能是否改善。
随机、观察者盲法、治疗对照试验。
三个大学门诊诊所。
39例接受含PI方案治疗且病毒复制得到抑制、空腹低密度脂蛋白（LDL）胆固醇大于3 mmol/l的HIV感染者。
患者被随机分配继续使用当前的PI或换用未增强的阿扎那韦。
第24周的终点指标为通过肱动脉血流介导的血管舒张（FMD）评估的内皮功能、血脂谱以及血清炎症和氧化应激参数。
两个治疗组的基线特征和平均FMD值具有可比性（阿扎那韦组为3.9%（标准差1.8），对照组为4.0%（标准差1.5））。治疗24周后，FMD分别降至3.3%（标准差1.4）和3.4%（标准差1.7）（所有p值均无统计学意义）。两组的总胆固醇均有所改善（分别为p<0.0001和p = 0.01），但阿扎那韦组的变化更明显（组间变化p = 0.05）。阿扎那韦组的高密度脂蛋白和甘油三酯水平有所改善（分别为p = 0.03和p = 0.003），而对照组则无变化。血清炎症和氧化应激参数未改变；阿扎那韦组的氧化型LDL显著改善。
在有治疗经验的患者中，从另一种PI转换为阿扎那韦尽管血清脂质显著改善，但并未导致内皮功能改善。致动脉粥样硬化的血脂谱以及抗逆转录病毒药物对内皮的直接作用可能会影响血管功能。
NCT00447070。
