接受抑制性抗逆转录病毒治疗的老年HIV阳性成年人的凝血失衡与神经认知功能
Coagulation imbalance and neurocognitive functioning in older HIV-positive adults on suppressive antiretroviral therapy.
作者信息
Montoya Jessica L, Iudicello Jennifer, Oppenheim Hannah A, Fazeli Pariya L, Potter Michael, Ma Qing, Mills Paul J, Ellis Ronald J, Grant Igor, Letendre Scott L, Moore David J
机构信息
aSDSU/UCSD Joint Doctoral Program in Clinical Psychology bDepartment of Psychiatry cDepartment of Family Medicine and Public Health dDepartment of Neurosciences eDepartment of Medicine, University of California, San Diego, La Jolla, California fDepartment of Pharmacy Practice, University of Buffalo, Buffalo, New York, USA.
出版信息
AIDS. 2017 Mar 27;31(6):787-795. doi: 10.1097/QAD.0000000000001404.
OBJECTIVES
The aim of this study was to compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV.
DESIGN
A cross-sectional study of 66 antiretroviral therapy treated, virally suppressed, HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults.
METHODS
Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor and von Willebrand factor), anticoagulation (antithrombin, protein C and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1 and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning.
RESULTS
Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4 cell count was 654 cells/μl. Levels of soluble biomarkers of procoagulation, anticoagulation and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers.
CONCLUSIONS
Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the cause of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy, thereby improving neurocognitive outcomes.
目的
本研究旨在比较HIV感染者与未感染HIV的对照者之间的血浆凝血生物标志物，并评估凝血紊乱对HIV患者神经认知功能的影响。
设计
一项横断面研究，纳入66例接受抗逆转录病毒治疗、病毒得到抑制的HIV感染者和34例未感染HIV的老年（≥50岁）成年人。
方法
参与者完成标准化的神经行为和神经医学评估。使用经过充分验证的综合神经心理测试组评估神经认知功能。收集与促凝（纤维蛋白原、p-选择素、组织因子和血管性血友病因子）、抗凝（抗凝血酶、蛋白C和血栓调节蛋白）、纤维蛋白溶解（D-二聚体、纤溶酶原激活物抑制剂-1和纤溶酶原）相关的血浆生物标志物。采用多变量线性回归来检验HIV与凝血在神经认知功能方面的相互作用。
结果
大多数参与者为男性（78.0%）且是非西班牙裔白人（73.0%），平均年龄为57.8岁。在HIV感染者中，HIV感染的平均估计持续时间为19.4年，当前CD4细胞计数中位数为654个/μl。促凝、抗凝和纤维蛋白溶解的可溶性生物标志物水平在HIV血清学状态组之间具有可比性。凝血与HIV对神经认知功能有相互作用，即凝血失衡越严重，HIV感染者的神经认知功能越差。凝血对神经认知的调节作用由促凝生物标志物而非抗凝或纤维蛋白溶解生物标志物驱动。
结论
促凝剂水平升高可能对老年HIV感染者的神经认知功能产生特别有害的影响。更好地理解凝血在HIV相关神经认知障碍病因中的具体作用，可能会带来旨在减少凝血病的治疗方法，从而改善神经认知结果。
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