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

项目总结/摘要 这项拟议的研究将调查丙型肝炎病毒（HCV）如何影响心血管疾病（CVD）的风险 在同时感染HIV和HCV的个体中： 具体目标1。为了量化HCV合并感染对急性心肌梗死（AMI）风险的影响， 在一个大型前瞻性临床护理队列中纵向随访的HIV感染患者队列 HIV感染会增加CVD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HCV的患者进一步增加了CVD风险，这种相互作用是否受到以下因素的影响： 年龄和HCV治疗状况尚不清楚。重要的是，即使在治疗后，CVD风险也可能持续存在。 HCV，这个问题以前没有回答过。据推测，存在两种慢性 感染将增加风险，超出单独感染的风险。 具体目标2。为了研究是否治疗HCV，并减少其相关的慢性炎症， 降低发生AMI的风险 HCV护理的新时代为HCV带来了极其有效的治疗，但获得仍然有限， 合并感染患者的治疗障碍持续存在。HCV治疗的肝外效应-特别是 直接作用的抗病毒药物（DAA）-未知。随着HCV治疗的持续障碍， HCV治疗是否可以降低CVD风险将对优先考虑 患者进行HCV治疗。 具体目标3。评估HCV合并感染对HIV患者CVD风险预测的影响 已建立的CVD风险预测算法是否能准确评估HIV/HCV共感染的风险， 受感染的患者仍不清楚，特别是在合并感染的患者中。我们建议评估几个 在一个大的合并感染患者队列中建立算法。通过创新分析，我们将 将HCV作为一种新的CVD危险因素纳入风险预测函数，以尝试改进模型 艾滋病的表现。 为了实现拟议的目标，并最大限度地增加HIV/HCV合并感染者的数量，我们将利用 北美最大的观察性艾滋病毒队列合作--北美艾滋病队列 研究与设计合作（NA-ACCORD）。这是一个非常适合的群体， 样本量、裁定的CVD事件和严格维护的数据。我们的多学科团队包括 国际公认的流行病学和生物统计学合作者，具有先进的 因果推理和CVD风险预测模型。这项及时和临床相关的研究将推动 通过产生关于HCV对CVD风险影响的新知识， 艾滋病病毒感染者的护理。

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.