Wohl David A, Arnoczy Gretchen, Fichtenbaum Carl J, Campbell Thomas, Taiwo Babafemi, Hicks Charles, McComsey Grace A, Koletar Susan, Sax Paul, Tebas Pablo, Ha Belinda, Massengale Kelly, Walsh Kendall, Stein James H
Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA.
Antivir Ther. 2014;19(2):141-7. doi: 10.3851/IMP2681. Epub 2013 Aug 28.
The association between abacavir (ABC) and cardiovascular disease (CVD) risk in HIV-infected individuals is unclear. Putative mechanisms for an effect of ABC on CVD risk including endothelial dysfunction have been proposed; however, a biological mechanism has not been established.
This was a cross-sectional study of HIV-infected subjects with HIV RNA levels <400 copies/ml, who were randomly assigned to ABC or tenofovir (TDF) as initial therapy during a prior clinical trial. A small cohort of subjects on zidovudine (AZT; not randomly assigned) were studied to explore long-term exposure to this agent. All underwent brachial artery ultrasound for flow-mediated dilation (FMD), and D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and fasting lipids were measured. Between-arm differences were evaluated by multivariable linear or logistic regression modelling.
There were 148 subjects (46 on ABC, 72 on TDF and 30 on AZT). Demographic characteristics were balanced across the groups except, as expected, AZT-treated participants were older, had higher CD4(+) T-cell counts, and longer antiretroviral therapy duration. After adjusting for age, brachial artery diameter, and treatment duration, FMD was similar in those on ABC (3.9%) and TDF (5.4%; P=0.181). FMD was higher in those on AZT (6.1%; P<0.005). Levels of IL-6, hsCRP and detectable D-dimer were similar between groups.
Among individuals assigned to ABC or TDF in randomized clinical trials there were no significant differences in FMD or markers of inflammation and coagulation. Whether ABC contributes to risk of CVD remains unclear, but our results suggest that endothelial dysfunction, heightened inflammation, and altered coagulation are unlikely to be mechanisms by which the drug could increase CVD risk above that seen with TDF.
在感染人类免疫缺陷病毒（HIV）的个体中，阿巴卡韦（ABC）与心血管疾病（CVD）风险之间的关联尚不清楚。已提出ABC影响CVD风险的潜在机制，包括内皮功能障碍；然而，尚未确立生物学机制。
这是一项针对HIV RNA水平<400拷贝/毫升的HIV感染受试者的横断面研究，这些受试者在先前的一项临床试验中被随机分配接受ABC或替诺福韦（TDF）作为初始治疗。对一小群接受齐多夫定（AZT；非随机分配）治疗的受试者进行了研究，以探讨长期接触该药物的情况。所有受试者均接受肱动脉超声检查以评估血流介导的血管舒张功能（FMD），并检测D-二聚体、高敏C反应蛋白（hsCRP）、白细胞介素-6（IL-6）和空腹血脂。通过多变量线性或逻辑回归模型评估组间差异。
共有148名受试者（46名接受ABC治疗，72名接受TDF治疗，30名接受AZT治疗）。除了如预期的那样，接受AZT治疗的参与者年龄较大、CD4(+)T细胞计数较高且抗逆转录病毒治疗持续时间较长外，各群体的人口统计学特征均衡。在调整年龄、肱动脉直径和治疗持续时间后，接受ABC治疗者的FMD（3.9%）与接受TDF治疗者（5.4%；P=0.181）相似。接受AZT治疗者的FMD较高（6.1%；P<0.005）。各组间IL-6、hsCRP和可检测到的D-二聚体水平相似。
在随机临床试验中，接受ABC或TDF治疗的个体在FMD或炎症及凝血标志物方面无显著差异。ABC是否会增加CVD风险仍不清楚，但我们的结果表明，内皮功能障碍、炎症加剧和凝血改变不太可能是该药物导致CVD风险高于TDF的机制。
