Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands; and.
J Acquir Immune Defic Syndr. 2021 May 1;87(1):711-719. doi: 10.1097/QAI.0000000000002633.
D-dimer concentrations in people living with HIV (PLHIV) on combination antiretroviral therapy (cART) are increased and have been linked to mortality. D-dimer is a biomarker of in vivo coagulation. In contrast to reports on D-dimer, data on coagulation capacity in PLHIV are conflicting. In this study, we assessed the effect of cART and inflammation on coagulation capacity.
We explored coagulation capacity using calibrated thrombin generation (TG) and linked this to persistent inflammation and cART in a cross-sectional study including PLHIV with viral suppression and uninfected controls.
We used multivariate analyses to identify independent factors influencing in vivo coagulation (D-dimer) and ex vivo coagulation capacity (TG).
Among 208 PLHIV, 94 (45%) were on an abacavir-containing regimen. D-dimer levels (219.1 vs 170.5 ng/mL, P = 0.001) and inflammatory makers (sCD14, sCD163, and high-sensitive C-reactive protein) were increased in PLHIV compared with those in controls (n = 56). PLHIV experienced lower TG (reflected by endogenous thrombin potential [ETP]) when compared with controls, after correction for age, sex, and antiretroviral therapy. Abacavir use was independently associated with increased ETP. Prothrombin concentrations were strongly associated with ETP and lower in PLHIV on a non-abacavir-containing regimen compared with those in controls, suggesting consumption as a possible mechanism for HIV-associated reduction in TG. D-dimer concentrations were associated with inflammation, but not TG.
Abacavir use was associated with increased TG and could serve as an additional factor in the reported increase in thrombotic events during abacavir use. Increased exposure to triggers that propagate coagulation, such as inflammation, likely underlie increased D-dimer concentrations found in most PLHIV.
接受联合抗逆转录病毒疗法（cART）的艾滋病毒感染者（PLHIV）的 D-二聚体浓度升高，并与死亡率相关。D-二聚体是体内凝血的生物标志物。与 D-二聚体的报告相反，PLHIV 凝血能力的数据存在矛盾。在这项研究中，我们评估了 cART 和炎症对凝血能力的影响。
我们使用校准的凝血酶生成（TG）来探索凝血能力，并在一项包括病毒抑制的 PLHIV 和未感染对照的横断面研究中，将其与持续炎症和 cART 联系起来。
我们使用多元分析来确定影响体内凝血（D-二聚体）和体外凝血能力（TG）的独立因素。
在 208 名 PLHIV 中，94 名（45%）接受了含有阿巴卡韦的方案。与对照组（n=56）相比，PLHIV 的 D-二聚体水平（219.1 与 170.5ng/mL，P=0.001）和炎症标志物（sCD14、sCD163 和高敏 C 反应蛋白）升高。在调整年龄、性别和抗逆转录病毒疗法后，PLHIV 的 TG（反映为内源性凝血酶潜能[ETP]）低于对照组。阿巴卡韦的使用与 ETP 的增加独立相关。与对照组相比，接受不含阿巴卡韦方案的 PLHIV 的凝血酶原浓度与 ETP 强烈相关，且较低，提示消耗可能是 HIV 相关 TG 降低的一种机制。D-二聚体浓度与炎症相关，但与 TG 无关。
阿巴卡韦的使用与 TG 的增加相关，可能是阿巴卡韦使用时报告的血栓事件增加的另一个因素。暴露于促凝血的触发因素（如炎症）的增加，可能是大多数 PLHIV 中发现的 D-二聚体浓度升高的基础。
