Cardiovascular Risk Reduction in an Aging HIV-Infected Population: The Impact of HCV Co-Infection

项目摘要/摘要 这项拟议的研究将调查丙型肝炎病毒(HCV)对心血管疾病(CVD)风险的影响 在同时感染艾滋病毒和丙型肝炎病毒的人中： 具体目的1.量化丙型肝炎病毒混合感染对急性心肌梗死(AMI)风险的影响 一组艾滋病毒感染患者纵向跟踪了一组大型前瞻性临床护理队列。 艾滋病毒感染增加了心血管疾病的风险，这种风险被认为是由非传统风险因素驱动的。是否 合并感染丙型肝炎病毒的患者进一步增加了心血管疾病的风险，这种相互作用是否受到 年龄和丙型肝炎病毒的治疗状况还不清楚。重要的是，即使在接受治疗后，心血管疾病的风险也可能持续存在。 丙型肝炎病毒，这个问题以前没有得到回答。假设有两种慢性病的存在 感染将增加风险，而不仅仅是任何一种感染。 具体目的2.研究治疗丙型肝炎病毒，并减少其相关的慢性炎症， 降低发生急性心肌梗死的风险 丙型肝炎病毒护理的新时代为丙型肝炎病毒带来了极其有效的治疗，但获得治疗的机会仍然有限 在合并感染的患者中，治疗障碍依然存在。丙型肝炎病毒治疗的肝外影响--特别是 直接作用抗病毒药物(DAA)--尚不为人所知。在丙型肝炎治疗的持续障碍下，了解 丙型肝炎病毒治疗是否可以降低心血管疾病的风险将对优先考虑的公共卫生问题产生重要影响 接受根治性丙型肝炎治疗的患者。 具体目的3.评估丙型肝炎病毒混合感染对预测HIV患者心血管疾病风险的影响 已建立的心血管疾病风险预测算法是否提供了对艾滋病毒/丙型肝炎联合感染风险的准确评估 感染患者仍不清楚，特别是在合并感染的患者中。我们建议评估几个 在一大群合并感染的患者中建立了算法。通过创新分析，我们将 将丙型肝炎病毒作为一种新的心血管疾病危险因素纳入风险预测函数，试图改进模型 在艾滋病方面的表现。 为了实现拟议的目标并最大限度地增加艾滋病毒/丙型肝炎病毒混合感染者的数量，我们将利用 北美最大的艾滋病毒观察组合作--北美艾滋病组 研究与设计合作(NA-ACCORD)。这是一个独一无二的非常合适的群体，因为它的 样本大小、判定的心血管事件和严格保存的数据。我们的多学科团队包括 国际知名的流行病学和生物统计学合作者，在先进的方法方面具有专业知识 因果推断和心血管疾病风险预测建模。这项及时且具有临床意义的研究将推动 通过产生关于丙型肝炎病毒对心血管疾病风险的影响的新知识，并将直接影响长期 照顾老龄化的艾滋病毒人群。

PROJECT SUMMARY/ABSTRACT The proposed study will investigate how Hepatitis C virus (HCV) impacts cardiovascular disease (CVD) risk among individuals co-infected with HIV and HCV: Specific Aim 1. To quantify the impact of HCV co-infection on acute myocardial infarction (AMI) risk in a cohort of HIV-infected patients followed longitudinally in a large prospective clinical care cohort HIV infection increases CVD risk, and this risk is thought to be driven by non-traditional risk factors. Whether patients co-infected with HCV have further increased CVD risk and whether this interaction is influenced by age and HCV treatment status is not well understood. Importantly, CVD risk may persist even after treated HCV, and this question has not been previously answered. It is hypothesized that the presence of two chronic infections will increase risk beyond that of either infection alone. Specific Aim 2. To investigate whether treating HCV, and reducing its associated chronic inflammation, decreases risk of incident AMI The new era of HCV care has brought extremely effective treatment for HCV, yet access remains limited and barriers to treatment persist in co-infected patients. The extra-hepatic effects of HCV treatment – particularly direct-acting antivirals (DAAs) – are not known. With persistent barriers to HCV treatment, knowledge of whether HCV treatment can reduce CVD risk will have important public health implications for prioritizing patients for curative HCV treatment. Specific Aim 3. To assess the impact of HCV co-infection on CVD risk prediction in HIV Whether established CVD risk prediction algorithms provide an accurate assessment of risk in HIV/HCV co- infected patients remains unclear, particularly among co-infected patients. We propose to assess several established algorithms in a large cohort of co-infected patients. Through innovative analyses, we will incorporate HCV as a novel CVD risk factor into risk prediction functions to attempt to improve model performance in HIV. To complete the proposed aims and maximize the number of HIV/HCV co-infected individuals, we will leverage the largest collaboration of observational HIV cohorts in North America – the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). This is a uniquely well-suited cohort given its large sample size, adjudicated CVD events, and rigorously maintained data. Our multidisciplinary team includes internationally regarded epidemiology and biostatistics collaborators with expertise in methods of advanced causal inference and in CVD risk prediction modeling. This timely and clinically relevant study will advance the field by generating new knowledge on the impact of HCV on CVD risk and will directly impact the long-term care of aging HIV populations.