HIV, Depression, and Cardiovascular Risk

 描述(申请人提供)：尽管抗逆转录病毒疗法(ART)提高了存活率，但艾滋病毒感染患者患慢性合并症的风险仍然较高，包括心血管疾病(HIV-CVD)。循环中白细胞介素6(IL-6)、超敏C反应蛋白和D-二聚体水平升高与HIV-CVD风险增加相关。此外，血管内皮细胞功能障碍似乎在接受抗逆转录病毒治疗的HIV感染患者中也很常见。然而，ART仅部分降低了这些炎症和凝血生物标志物，并仅部分改善了血管内皮细胞的功能，这是通过测量肱动脉的血流介导的扩张(FMD)来衡量的。尽管迄今为止被完全忽视的抗逆转录病毒疗法，但艾滋病毒-心血管疾病风险持续上升的一个潜在解释是抑郁。由于在接受抗逆转录病毒治疗的艾滋病毒感染患者中有20%-40%存在抑郁障碍，因此这种常见的共病可能是艾滋病毒心血管疾病风险持续上升的原因之一。这项应用的中心目标是确定艾滋病毒感染者的抑郁障碍及其治疗与全身炎症/凝血和内皮功能之间的关系。我们将通过以下具体目标来解决这一目标：具体目标1：确定抑郁症和暴露于抑郁症的治疗与全身炎症和艾滋病毒凝血改变的相关性。我们将对大型(N=1525)退伍军人老龄化队列研究(VAS)生物标记物队列进行观察性分析，其中还包括患者健康问卷(PHQ)-9分数、广泛的药物处方数据以及抑郁症和心理治疗的诊断代码；具体目标2：确定认知行为治疗对HIV感染的成年抑郁症患者全身炎症、凝血功能改变和内皮功能障碍的影响。我们将通过对印第安纳大学110名HIV-1RNA水平被抑制、PHQ-9定义为严重抑郁症的ART治疗患者进行为期24周的随机试验，对这些患者进行为期24周的试点试验，该试验使用Beat the Blues认知行为治疗计划。我们的多学科研究团队拥有成功实现这些目标所需的专业知识和资源。这些研究的结果将通过利用现有的HIV-CVD队列和进行一项新的介入性先导性试验来确定HIV感染患者的抑郁、抑郁治疗、炎症/凝血和内皮功能之间的关系。因此，这项申请符合RFA HL-14-023规定的目标，并将为未来通过治疗抑郁症来减少艾滋病毒-心血管事件的介入试验提供理论基础。这一系列研究可能为艾滋病毒临床医生提供新的、易于实施的工具，以预防患者的心血管疾病发病率和死亡率，并将推动艾滋病毒-心血管疾病研究领域的发展。

 DESCRIPTION (provided by applicant): Despite the improved survival with antiretroviral therapy (ART), HIV-infected patients still remain at higher risk for chronic comorbidities, including cardiovascular disease (HIV-CVD). Elevated circulating levels of interleukin-6 (IL-6), hsCRP, and D-dimer are associated with increased risks of HIV-CVD. In addition, endothelial dysfunction also appears to be common in ART-treated, HIV-infected patients. However, ART only partially lowers these inflammatory and coagulation biomarkers and only partially improves endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery. One potential explanation for the continued heightened risk of HIV-CVD despite ART that has thus far been completely ignored is depression. Because depressive disorders are found in 20-40% of HIV-infected patients receiving ART, it stands to reason that this common comorbidity may contribute to the persistently elevated risk of CVD in HIV. The central objective of this application is to determine the relationships between depressive disorders and its treatments with systemic inflammation/coagulation and endothelial function in HIV-infected persons. We will address this objective with the following Specific Aims: Specific Aim #1: To determine the associations of depression and exposure to depression treatment with systemic inflammation and altered coagulation in HIV. We will conduct an observational analysis of the large (N=1525) Veterans Aging Cohort Study (VACS) Biomarker Cohort which also includes Patient Health Questionnaire (PHQ)-9 scores, extensive pharmaceutical prescription data, and diagnostic codes for depression and psychotherapy; Specific Aim #2: To determine the effects of cognitive behavioral treatment on systemic inflammation, altered coagulation, and endothelial dysfunction in HIV-infected adults with depression. We will address this aim by conducting a pilot, randomized, 24-week trial using the Beating the Blues cognitive behavioral treatment program in 110 ART-treated patients at Indiana University with suppressed HIV-1 RNA levels and with PHQ-9 defined major depression. Our multidisciplinary research team has the required expertise and resources to successfully address these Aims. The results of these studies will determine the relationships between depression, depression treatment, inflammation/coagulation, and endothelial function in HIV-infected patients by leveraging an existing HIV-CVD cohort and by performing a novel, interventional, pilot trial. As such, this application meets the stated objectives of RFA HL-14-023 and will provide the rationale for future interventional trials to reduce HIV-CVD events by treating depression. This line of research may provide HIV clinicians with novel and easily implementable tools to prevent CVD morbidity and mortality in their patients and will advance the field of HIV- CVD research.