抗逆转录病毒疗法的启动对HIV-1感染中单核细胞、内皮细胞和血小板功能的影响。

The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection.

作者信息

O'Halloran J A, Dunne E, Gurwith Mmp, Lambert J S, Sheehan G J, Feeney E R, Pozniak A, Reiss P, Kenny D, Mallon Pwg

机构信息

HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.

Cardiovascular Biology Group, Royal College of Surgeons in Ireland, Dublin, Ireland.

出版信息

HIV Med. 2015 Nov;16(10):608-19. doi: 10.1111/hiv.12270. Epub 2015 Jun 25.

DOI:10.1111/hiv.12270

PMID:26111187

Abstract

OBJECTIVES

Monocyte activation, endothelial dysfunction and platelet activation all potentially contribute to the increased risk of cardiovascular disease (CVD) reported in those with HIV-1 infection. To date, no study has examined how initiation of antiretroviral therapy (ART) affects markers of all three processes. We aimed to compare markers of monocyte, endothelial and platelet function between untreated HIV-positive subjects and HIV-negative controls and to examine the early effects of ART initiation on these markers.

METHODS

We measured monocyte [soluble CD14 (sCD14) and sCD163], endothelial [von Willebrand factor (vWF), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1)] and platelet [soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L) and soluble glycoprotein VI (sGPVI)] biomarkers before and at weeks 4 and 12 post ART initiation in HIV-positive and well-matched HIV-negative controls.

RESULTS

We examined 40 subjects, 25 HIV-positive subjects and 15 controls, with a median age of 34 years [interquartile range (IQR) 31, 40 years], of whom 60% were male and 47.5% Caucasian. Pre-ART, all biomarkers (monocyte, endothelial and platelet) were significantly higher in HIV-positive patients versus controls (all P < 0.05) and decreased with ART initiation, except for sCD14, which remained unchanged [median 1680 (IQR 1489, 1946) ng/mL at week 12 versus 1570 (IQR 1287, 2102) ng/mL at week 0; P = 0.7]. Although platelet activation markers reduced to levels comparable to those in controls, endothelial dysfunction markers remained elevated, as did sCD163 [at week 12, median 1005 (IQR 791, 1577) ng/mL in HIV-positive patients versus 621 (IQR 406, 700) ng/mL in controls; P < 0.0001].

CONCLUSIONS

ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.

摘要

目的

单核细胞活化、内皮功能障碍和血小板活化都可能导致人类免疫缺陷病毒1型（HIV-1）感染者心血管疾病（CVD）风险增加。迄今为止，尚无研究探讨抗逆转录病毒疗法（ART）的启动如何影响这三个过程的标志物。我们旨在比较未接受治疗的HIV阳性受试者和HIV阴性对照者之间单核细胞、内皮细胞和血小板功能的标志物，并研究ART启动对这些标志物的早期影响。

方法

我们在HIV阳性且匹配良好的HIV阴性对照者开始ART治疗前、治疗后4周和12周测量了单核细胞[可溶性CD14（sCD14）和sCD163]、内皮细胞[血管性血友病因子（vWF）、细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）]以及血小板[可溶性P-选择素（sP-选择素）、可溶性CD40配体（sCD40L）和可溶性糖蛋白VI（sGPVI）]生物标志物。

结果

我们研究了40名受试者，其中25名HIV阳性受试者和15名对照者，中位年龄为34岁[四分位间距（IQR）31，40岁]，其中60%为男性，47.5%为白种人。在开始ART治疗前，HIV阳性患者的所有生物标志物（单核细胞、内皮细胞和血小板）均显著高于对照者（所有P<0.05），且随着ART治疗的启动而降低，但sCD14除外，其保持不变[第12周时中位数为1680（IQR 1489，1946）ng/mL，而第0周时为1570（IQR 1287，2102）ng/mL；P=0.7]。尽管血小板活化标志物降至与对照者相当的水平，但内皮功能障碍标志物仍升高，sCD163也是如此[第12周时，HIV阳性患者中位数为1005（IQR 791，1577）ng/mL，而对照者为621（IQR 406，700）ng/mL；P<0.0001]。