在WIHS研究中，HIV感染女性在接受高效抗逆转录病毒治疗（HAART）前后的T细胞活化水平与6.5年期间的颈动脉僵硬度相关。
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.
作者信息
Karim Roksana, Mack Wendy J, Kono Naoko, Tien Phyllis C, Anastos Kathryn, Lazar Jason, Young Mary, Desai Seema, Golub Elizabeth T, Kaplan Robert C, Hodis Howard N, Kovacs Andrea
机构信息
*Maternal, Child and Adolescent Center for Infectious Disease and Virology, Department of Pediatrics, University of Southern California, Los Angeles, CA; †Department of Preventive Medicine, University of Southern California, Los Angeles, CA; ‡Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA; §Department of Medicine, University of California, San Francisco, San Francisco, CA; ‖Medical Service, Department of Veterans Affairs, University of California, San Francisco, San Francisco, CA; ¶Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY; #Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, Brooklyn, NY; **Georgetown University Medical Center, Georgetown University, Washington, DC; ††Departments of Medicine, Stroger Hospital and Rush University, Chicago, IL; ‡‡Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and §§Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
出版信息
J Acquir Immune Defic Syndr. 2014 Nov 1;67(3):349-56. doi: 10.1097/QAI.0000000000000311.
OBJECTIVE
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 comorbidity in HIV infection. We hypothesized that T-cell activation will predict vascular stiffness, a measure of subclinical atherosclerosis.
DESIGN
Linear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness.
METHODS
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 coinfected) women in the Women's Interagency HIV Study. T-cell activation was defined by CD8⁺CD38⁺DR+ and CD4⁺CD3⁺8DR+. Multiple activation assessments over 6.5 years were averaged. In 140 women, T-cell activation was measured before and after highly active antiretroviral therapy (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.
RESULTS
Percentages of CD4⁺ and CD8⁺ T-cell activation were significantly higher in HIV- infected compared with 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 levels significantly predicted increased arterial stiffness independent of CD4⁺ cell count and HIV RNA. The association was stronger among HIV/hepatitis C-coinfected women compared with HIV-monoinfected 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.
CONCLUSIONS
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.
目的
T细胞活化是推动HIV疾病进展的主要途径。关于T细胞活化对HIV相关动脉粥样硬化和心血管疾病（HIV感染中常见的合并症）的影响，我们所知甚少。我们假设T细胞活化将预示血管硬度，这是亚临床动脉粥样硬化的一项指标。
设计
线性回归模型评估了T细胞活化与血管硬度的协变量调整关联。
方法
在女性机构间HIV研究中，通过流式细胞术评估了59名HIV阴性和376名HIV感染（185名合并丙型肝炎感染）女性的CD4⁺和CD8⁺T细胞上CD38和HLA - DR的表达。T细胞活化由CD8⁺CD38⁺DR⁺和CD4⁺CD3⁺8DR⁺定义。对6.5年期间的多次活化评估进行平均。在140名女性中，在开始高效抗逆转录病毒治疗（HAART）之前和之后测量T细胞活化。在最后一次测量T细胞活化后中位数6.5年完成颈动脉超声检查，并计算包括扩张性和弹性在内的颈动脉硬度。
结果
与HIV阴性女性相比，HIV感染女性中CD4⁺和CD8⁺T细胞活化百分比显著更高。在HIV阴性女性中，T细胞活化与颈动脉硬度无关。在HIV感染女性中，较高的CD4⁺T细胞活化水平显著预示动脉硬度增加，独立于CD4⁺细胞计数和HIV RNA。与单纯HIV感染女性相比，HIV/丙型肝炎合并感染女性中的关联更强；然而，差异无统计学意义（交互作用P>0.05）。HAART治疗前后的CD4⁺T细胞活化水平显著预示颈动脉硬度。
结论
即使在开始HAART治疗后，持续的T细胞活化也可能导致血管结构和/或功能损害，加速HIV感染中的动脉粥样硬化形成。这些结果需要在纵向前瞻性研究中得到证实。
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