炎症和 CD8 T 细胞活化标志物与 HIV 感染者亚临床颈动脉疾病相关，但与单核细胞活化标志物无关。
Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals.
机构信息
Harrington Heart and Vascular Institute, Cleveland, OH, USA.
出版信息
HIV Med. 2013 Jul;14(6):385-90. doi: 10.1111/hiv.12013. Epub 2013 Jan 18.
OBJECTIVES
The aim of the study was to explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1-infected patients on antiretroviral therapy (ART).
METHODS
Baseline mean common carotid artery (CCA) intima-media thickness (IMT) and carotid plaque (IMT > 1.5 cm) were evaluated in the first 60 subjects enrolled in the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial. All subjects were adults on stable ART with evidence of heightened T-cell activation (CD8(+)CD38(+)HLA-DR(+) ≥ 19%) or increased inflammation (high-sensitivity C-reactive protein ≥ 2 mg/L). All had fasting low-density lipoprotein (LDL) cholesterol ≤ 130 mg/dL.
RESULTS
Seventy-eight per cent of patients were men and 65% were African-American. Median (interquartile range) age and CD4 count were 47 (43, 52) years and 648 (511, 857) cells/μL, respectively. All had HIV-1 RNA < 400 HIV-1 RNA copies/mL. Mean CCA-IMT was correlated with log-transformed CD8(+)CD38(+)HLA-DR(+) percentage (r = 0.326; P = 0.043), and concentrations of interleukin-6 (r = 0.283; P = 0.028), soluble vascular cell adhesion molecule (sVCAM; r = 0.434; P = 0.004), tumour necrosis factor-α receptor-I (TNFR-I; r = 0.591; P < 0.0001) and fibrinogen (r = 0.257; P = 0.047). After adjustment for traditional cardiovascular disease (CVD) risk factors, the association with TNFR-I (P = 0.007) and fibrinogen (P = 0.033) remained significant. Subjects with plaque (n = 22; 37%) were older [mean (standard deviation) 51 (7.7) vs. 43 (9.4) years, respectively; P = 0.002], and had a higher CD8(+)CD38(+)HLA-DR(+) percentage [median (interquartile range) 31% (24, 41%) vs. 23% (20, 29%), respectively; P = 0.046] and a higher sVCAM concentration [mean (standard deviation) 737 (159) vs. 592 (160) ng/mL, respectively; P = 0.008] compared with those without plaque. Pro-inflammatory monocyte subsets and serum markers of monocyte activation (soluble CD163 and soluble CD14) were not associated with CCA-IMT or plaque.
CONCLUSIONS
Participants in SATURN-HIV have a high level of inflammation and immune activation that is associated with subclinical vascular disease despite low serum LDL cholesterol.
目的
本研究旨在探讨接受抗逆转录病毒治疗（ART）的 HIV-1 感染者中淋巴细胞和单核细胞激活、炎症与亚临床血管疾病之间的关系。
方法
在 Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV（SATURN-HIV）试验中，评估了前 60 名入组患者的颈总动脉内膜中层厚度（CCA-IMT）的平均基线值和颈动脉斑块（CCA-IMT > 1.5 cm）。所有受试者均为接受稳定 ART 治疗、存在 T 细胞高度激活（CD8(+)CD38(+)HLA-DR(+)≥19%）或炎症升高（高敏 C 反应蛋白≥2mg/L）证据的成年人。所有患者的空腹低密度脂蛋白（LDL）胆固醇均≤130mg/dL。
结果
78%的患者为男性，65%为非裔美国人。中位（四分位间距）年龄和 CD4 计数分别为 47（43，52）岁和 648（511，857）个/μL。所有患者的 HIV-1 RNA<400HIV-1 RNA 拷贝/mL。CCA-IMT 与对数转换的 CD8(+)CD38(+)HLA-DR(+)百分比呈正相关（r=0.326；P=0.043），与白细胞介素-6（r=0.283；P=0.028）、可溶性血管细胞黏附分子（sVCAM；r=0.434；P=0.004）、肿瘤坏死因子-α受体-I（TNFR-I；r=0.591；P<0.0001）和纤维蛋白原（r=0.257；P=0.047）浓度呈正相关。在校正传统心血管疾病（CVD）危险因素后，与 TNFR-I（P=0.007）和纤维蛋白原（P=0.033）的相关性仍然显著。存在斑块的患者（n=22；37%）年龄较大[平均（标准差）51（7.7）岁比 43（9.4）岁，P=0.002]，CD8(+)CD38(+)HLA-DR(+)百分比更高[中位数（四分位间距）31%（24，41%）比 23%（20，29%），P=0.046]，sVCAM 浓度更高[均值（标准差）737（159）ng/mL 比 592（160）ng/mL，P=0.008]。与无斑块患者相比。促炎单核细胞亚群和单核细胞激活的血清标志物（可溶性 CD163 和可溶性 CD14）与 CCA-IMT 或斑块均无相关性。
结论
尽管 SATURN-HIV 参与者的血清 LDL 胆固醇水平较低，但仍存在高水平的炎症和免疫激活，与亚临床血管疾病相关。
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