Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes after Hepatitis C Eradication (CHROME)

HIV 和丙型肝炎引起的心血管疾病：丙型肝炎根除后的风险结果 (CHROME)

• 批准号: 10244806
• 负责人: Henry Masur
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10244806
• 关键词: Acute; Age; Antiviral Agents; Baltimore; Biological Markers; C-reactive protein; Cardiac; Cardiovascular Diseases; Chronic; Development; Enrollment; Extrahepatic; Fibrosis; Funding; Gadolinium; General Population; HIV; HIV Seronegativity; HIV Seropositivity; HIV/HCV; Hepatitis C; Hepatitis C Therapy; Highly Active Antiretroviral Therapy; Immunologic Markers; Individual; Infection; Inflammation; Institutional Review Boards; Intervention; Life Expectancy; Liver; Longevity; Magnetic Resonance Imaging; Maryland; Microvascular Dysfunction; Morbidity - disease rate; Myocardial; Outcome; Patients; Pilot Projects; Population; Prospective Studies; Protocols documentation; Risk; United States National Institutes of Health; Universities; Virus Diseases; bench to bedside; cardiovascular disorder risk; cardiovascular risk factor; chronic infection; comorbidity; extracellular; immune activation; improved; mortality; myocardial injury; programs

Among people living with HIV (PLWH), there is a 50% increased risk of acute myocardial infection compared to the general population. Although the advent of highly active antiretroviral therapy (HAART) has had several benefits for PLWH,including increased life expectancy, the longer life span has also made this population apt to develop comorbidities seen in age-matched individuals without HIV, including cardiovascular disease. In addition, HAART itself is a risk factor for cardiovascular disease (CVD), and persistent inflammation and chronic immune activation caused by HIV and ART results in a proinflammatory state that also increases the risk for cardiovascular disease. Hepatitis C (HCV) is another chronic viral infection with significant morbidity and mortality. The development of directly acting antivirals (DAAs) has dramatically improved the cure rate of HCV treatment. However, besides the effects on the liver, chronic infection with HCV leads to numerous extrahepatic manifestations that are associated with morbidity and mortality, including cardiovascular disease. Therefore, patients co-infected with HCV and HIV have a magnified cardiovascular risk than that of the general population. If treatment of HCV can lower the risk of CVD among HIV and HCV co-infected patients, then this would provide an indication for early HCV treatment in this population. As such, we have initiated a pilot, intervention, non-randomized, controlled prospective study to treat HCV in mono-infected and HIV co-infected individuals and compare cardiovascular risk outcomes to HIV mono-infected controls. This pilot study will demonstrate whether functional cure of HCV reduces myocardial injury and risk of cardiovascular disease. The proposal was funded by the Bench-to-Bedside program at NIH and the IHV ID Department and Merck. The MRIs will be done at the NIH. The IRB of Record will be the University of Maryland Baltimore. The protocol has enrolled 33 patients and should complete enrollment in 2020.

在艾滋病毒感染者（PLWH）中，与普通人群相比，急性心肌感染的风险增加了50%。尽管高效抗逆转录病毒疗法（HAART）的出现对PLWH有几个好处，包括延长预期寿命，但较长的寿命也使这一人群容易患上年龄匹配的无艾滋病毒个体的合并症，包括心血管疾病。此外，HAART本身是心血管疾病（CVD）的危险因素，并且由HIV和ART引起的持续炎症和慢性免疫激活导致促炎状态， 增加患心血管疾病的风险。 丙型肝炎（HCV）是另一种慢性病毒感染，具有显著的发病率和死亡率。直接作用的抗病毒药物（DAA）的发展显着提高了HCV治疗的治愈率。然而，除了对肝脏的影响外，HCV慢性感染还导致许多与发病率和死亡率相关的肝外表现，包括心血管疾病。因此，合并感染HCV和HIV的患者比一般人群具有更大的心血管风险。如果HCV治疗可以降低HIV和HCV合并感染患者的CVD风险，那么这将为该人群的早期HCV治疗提供指示。 因此，我们已经启动了一项试点，干预，非随机，对照前瞻性研究，以治疗HCV单感染和HIV合并感染的个体，并比较心血管风险结果与HIV单感染对照。这项初步研究将证明HCV的功能性治愈是否会降低心肌损伤和心血管疾病的风险。 该提案由NIH的Bench-to-Bedside计划、IHV ID部门和默克公司资助。MRI将在NIH进行。IRB记录为马里兰州巴尔的摩大学。 该方案已入组33例患者，应于2020年完成入组。