Elucidating Hepatitis C Infection as a Risk Factor for Coronary Heart Disease in HIV-Infected Patients

阐明丙型肝炎感染是 HIV 感染者患冠心病的危险因素

• 批准号: 10452333
• 负责人: Shashwatee Bagchi
• 金额: $ 4.34万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452333
• 关键词: AIDS/HIV problem; Adult; African American; Age; Angiography; Atherosclerosis; Baltimore; CD4 Positive T Lymphocytes; CD8B1 gene; CXCL10 gene; CXCL11 gene; CXCL9 gene; Cardiovascular system; Caucasians; Cessation of life; Chronic; Chronic Hepatitis C; Clinic; Clinical; Clinical Investigator; Cohort Studies; Communicable Diseases; Coronary; Coronary Arteriosclerosis; Coronary heart disease; Cross-Sectional Studies; Data; Disease; Disease Progression; Drug user; Epidemic; Extrahepatic; Feasibility Studies; General Population; Goals; HIV; HIV/HCV; HLA-DR Antigens; Heart Diseases; Heart Rate; Hepatitis C; Hepatitis C Therapy; Hepatitis C co-infection; Human; Illicit Drugs; Immune; Individual; Infection; Inflammation; Inflammatory; Institutes; Integration Host Factors; Interferon Type II; Interleukin-6; Intervention; Lead; Link; Liver Fibrosis; Manuscripts; Maryland; Measures; Morbidity - disease rate; Participant; Pathogenesis; Pathway interactions; Patients; Plasma; Population; Publishing; Recording of previous events; Retrospective cohort study; Risk; Risk Factors; Role; T memory cell; T-Cell Activation; TNF gene; Testing; Therapeutic Intervention; Time; United States; Universities; Update; Viral Proteins; Virus Diseases; Woman; Work; antiretroviral therapy; base; burden of illness; cardiovascular risk factor; cohort; coronary calcium scoring; coronary plaque; design; exhaust; exhaustion; heart disease risk; high risk; high risk population; immune activation; individual patient; inflammatory marker; inner city; male; medical schools; mortality; novel; preventive intervention; professor; programmed cell death protein 1; sex; therapeutic target; virology

PROJECT ABSTRACT The candidate is an Assistant Professor at the University of Maryland School of Medicine in Division of Infectious Disease and the Institute of Human Virology. The candidate's long-term goal is to become an independent clinical investigator and to contribute to the field of discovery in HIV/AIDS and hepatitis C (HCV). The specific focus is on identifying mechanistic pathways that confer the increased cardiovascular morbidity and mortality with hopes of developing therapeutic targets to reduce the burden of coronary heart disease (CHD) in these patients. The candidate has shown initiative by conducting a longitudinal retrospective cohort study of patients in one of the largest HIV clinics in inner-city Baltimore. Preliminary data demonstrated an association between chronic HCV infection and elevated risk scores for developing CHD in this high-risk population. This result led to the hypothesis for the proposed project as well as another pilot feasibility study evaluating coronary atherosclerosis using coronary CT angiography in these patients. Two manuscripts have been published, and four others are in review related to this work. Rates of CHD are over twice as high in HIV-infected compared to matched uninfected controls, but factors contributing to increased risk of CHD in HIV-infected patients remain to be clearly elucidated. Many studies suggest that HCV co-infection is associated with increased rates of CHD in HIV-infected patients, but results have been mixed. Preliminary data from the candidate’s work suggest that HCV found an association between HCV and CHD in an inner- city, high-risk demographic group and therefore provides strong scientific premise to design a study that will more conclusively delineate this unresolved relationship between HCV and CHD. The goal of this proposal is to establish the extent to which chronic HCV infection increases the burden of CHD in HIV-infected patients, and to elucidate host inflammatory and immune pathways that predict increased CHD burden. We hypothesize that chronic HCV infection in HIV patients increases CHD risk by inducing inflammation and T cell activation that contribute to accelerated progression of CHD. To test our hypothesis, we will use novel non-interferon based therapy to eradicate HCV infection and test whether atherosclerosis decreases, and in doing so, establish a causal link between HCV and atherosclerosis. Identifying predictors of CHD progression from overlapping pathways could inform preventive and therapeutic intervention strategies to mitigate CHD progression in HIV/HCV co-infected patients.

项目摘要 候选人是一名助理教授，在马里兰州医学院， 传染病部和人类病毒学研究所。候选人的长期 我的目标是成为一名独立的临床研究者，并为发现领域做出贡献。 艾滋病毒/艾滋病和丙型肝炎（HCV）。具体的重点是确定机制途径 这使得心血管疾病的发病率和死亡率增加， 治疗目标是减少这些患者的冠心病（CHD）负担。 候选人通过进行纵向回顾性队列研究， 在巴尔的摩市中心一家最大的艾滋病诊所接受治疗。初步数据显示， 慢性HCV感染与冠心病发生风险评分升高之间的相关性 这个高危人群。这一结果导致了拟议项目的假设， 另一项使用冠状动脉CT评价冠状动脉粥样硬化的试点可行性研究 血管造影术。两份手稿已经出版，另外四份在 审查与这项工作有关。 HIV感染者的CHD发病率是未感染者的两倍多， 但导致HIV感染患者CHD风险增加的因素仍有待明确， 阐明。许多研究表明，HCV合并感染与HCV感染率增加有关。 艾滋病毒感染者的冠心病，但结果好坏参半。的初步数据 候选人的工作表明，HCV发现HCV和CHD之间的内在联系， 城市、高危人群，因此为设计一个 这项研究将更明确地描述HCV和CHD之间尚未解决的关系。 该提案的目标是确定慢性HCV感染在多大程度上增加了 HIV感染患者CHD的负担，并阐明宿主炎症和免疫 预测CHD负担增加的途径。我们假设HIV中的慢性HCV感染 患者通过诱导炎症和T细胞活化增加CHD风险， 加速CHD的进展。为了验证我们的假设，我们将使用新的非干扰素为基础的 治疗根除HCV感染和测试是否动脉粥样硬化减少，并在这样做， 建立HCV和动脉粥样硬化之间的因果关系。冠心病的预测因素 重叠途径的进展可以为预防和治疗干预提供信息 缓解HIV/HCV合并感染患者CHD进展的策略。

项目成果

Association of Soluble Markers of Inflammation With Peri-coronary Artery Inflammation in People With and Without HIV Infection and Without Cardiovascular Disease.

• DOI: 10.1093/ofid/ofad328
• 发表时间: 2023-08
• 期刊: Open forum infectious diseases
• 影响因子: 4.2

The Role of Multimodality Imaging in HIV-Associated Cardiomyopathy.

• DOI: 10.3389/fcvm.2021.811593
• 发表时间: 2021
• 期刊: Frontiers in cardiovascular medicine
• 影响因子: 3.6
• 作者: Gambahaya ET;Rana R;Bagchi S;Sharma G;Sarkar S;Goerlich E;Cupido B;Mukherjee M;Hays AG
• 通讯作者: Hays AG