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

项目概要/摘要 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) 风险 在同时感染 HIV 和 HCV 的个体中： 具体目标 1. 量化 HCV 合并感染对急性心肌梗死 (AMI) 风险的影响 在大型前瞻性临床护理队列中对一组 HIV 感染患者进行纵向跟踪 HIV 感染会增加 CVD 风险，而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 CVD 风险进一步增加，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，即使治疗后，CVD 风险也可能持续存在 HCV，这个问题以前没有得到回答。据推测，存在两种慢性病 感染会增加比单独感染任何一种感染的风险。 具体目标 2. 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 带来了极为有效的治疗方法，但获得途径仍然有限，并且 合并感染患者的治疗障碍依然存在。 HCV 治疗的肝外效应 – 特别是 直接作用抗病毒药物（DAA）——尚不清楚。由于 HCV 治疗持续存在障碍，对 HCV 治疗是否可以降低 CVD 风险将对公共卫生产生重要影响 接受 HCV 治愈性治疗的患者。 具体目标 3. 评估 HCV 合并感染对 HIV CVD 风险预测的影响 已建立的 CVD 风险预测算法是否可以准确评估 HIV/HCV 合并症的风险 感染患者的情况仍不清楚，特别是合并感染的患者。我们建议评估几个 在一大群同时感染的患者中建立了算法。通过创新分析，我们将 将 HCV 作为一种新型 CVD 风险因素纳入风险预测函数中，尝试改进模型 在艾滋病毒方面的表现。 为了完成拟议的目标并最大限度地增加 HIV/HCV 双重感染者的数量，我们将利用 北美最大的观察性艾滋病队列合作——北美艾滋病队列 研究与设计合作 (NA-ACCORD)。鉴于其规模庞大，这是一个非常适合的群体 样本量、裁定的 CVD 事件以及严格维护的数据。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，拥有先进方法的专业知识 因果推理和 CVD 风险预测模型。这项及时且与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，将直接影响长期 照顾老龄化的艾滋病毒人口。

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.