T-cell activation, both pre- and post-HAART levels, correlates with carotid artery stiffness over 6.5 years among HIV-infected women in the WIHS.
T-cell activation, both pre- and post-HAART levels, correlates with carotid artery stiffness over 6.5 years among HIV-infected women in the WIHS.
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DOI：
10.1097/qai.0000000000000311
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发表时间：
2014-11-01
期刊：
影响因子：
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通讯作者：
Kovacs A
中科院分区：
文献类型：
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作者：
Karim R;Mack WJ;Kono N;Tien PC;Anastos K;Lazar J;Young M;Desai S;Golub ET;Kaplan RC;Hodis HN;Kovacs A
T细胞激活是推动HIV疾病进展的主要途径。关于T细胞激活对HIV相关动脉粥样硬化和心血管疾病的影响，人们知之甚少，这是HIV感染中常见的共同发病率。我们假设T细胞激活将预测血管僵硬，这是亚临床动脉粥样硬化的一种衡量标准。线性回归模型评估了协变量调整后的T细胞激活与血管僵硬之间的关联。采用流式细胞术检测了女性机构间HIV研究(WIHS)中59例HIV阴性和376例HIV感染者(185例丙型肝炎合并感染)患者外周血中CD4+和CD8+T细胞表面CD38和HLA-DR的表达。T细胞活化由CD8+CD38+DR+和CD4+CD38+DR+定义。平均进行了超过6.5年的多次激活评估。在140名妇女中，检测了HAART开始前后T细胞的激活情况。最后一次测量T细胞活性和颈动脉硬度(包括扩张性和弹性)后，完成颈动脉超声检查，中位数为6.5年。HIV感染者的CD4+和CD8+T细胞激活百分率明显高于HIV阴性妇女。在HIV阴性的女性中，T细胞的激活与颈动脉僵硬无关。在感染HIV的女性中，较高的CD4+T细胞活性显著预示着动脉僵硬的增加，而不依赖于CD4细胞计数和HIV RNA。与单独感染HIV的女性相比，HIV/丙型肝炎病毒混合感染的女性之间的关联性更强；然而，这种差异在统计学上并不显著(p-交互作用&>0.05)。HAART前后CD4+T细胞活化水平显著预测颈动脉僵硬。持续的T细胞激活，即使在HAART开始后，也可能导致结构和/或功能血管损伤，加速HIV感染的动脉粥样硬化形成。这些结果需要在一项纵向前瞻性研究中得到证实。
T-cell activation is a major pathway driving HIV disease progression. Little is known regarding the impact of T-cell activation on HIV-associated atherosclerosis and cardiovascular disease, a common co-morbidity in HIV infection. We hypothesized that T-cell activation will predict vascular stiffness, a measure of subclinical atherosclerosis. Linear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness. CD38 and HLA-DR expression on CD4+ and CD8+ T-cells was assessed by flow cytometry among 59 HIV-negative and 376 HIV-infected (185 hepatitis-C co-infected) women in the Women's Interagency HIV Study (WIHS). T-cell activation was defined by CD8+CD38+DR+ and CD4+CD38+DR+. Multiple activation assessments over 6.5 years were averaged. In 140 women, T-cell activation was measured before and after HAART initiation. Carotid artery ultrasounds were completed a median of 6.5 years after last measurement of T- cell activation and carotid artery stiffness including distensibility and elasticity were calculated. Percentages of CD4+ and CD8+ T-cell activation were significantly higher in HIV- infected compared to HIV-negative women. Among HIV-negative women, T-cell activation was not associated with carotid artery stiffness. Among HIV-infected women, higher CD4+ T-cell activation significantly predicted increased arterial stiffness independent of CD4 cell count and HIV RNA. The association was stronger among HIV/HCV co-infected compared to HIV-mono- infected women; however, the difference was not statistically significant (p-for interaction>0.05). Pre- and post-HAART levels of CD4+ T-cell activation significantly predicted carotid artery stiffness. Persistent T-cell activation, even after HAART initiation, can contribute to structural and/or functional vascular damage accelerating atherogenesis in HIV infection. These results need to be confirmed in a longitudinal prospective study.