HIV/HCV-related health disparities in Baltimore: from community to lab bench

巴尔的摩与艾滋病毒/丙型肝炎相关的健康差异：从社区到实验室工作台

• 批准号: 10372120
• 负责人: Yun-Chi Chen
• 金额: $ 24.8万
• 依托单位: MORGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-31 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372120
• 关键词: Address; Affect; African American population; Baltimore; Basic Science; Biological Models; Biological Response Modifiers; CD4 Positive T Lymphocytes; Caring; Cell Surface Receptors; Characteristics; Chronic; Chronic Hepatitis C; Cities; Clinical Sciences; Code; Cohort Studies; Communities; Data; Databases; Epidemic; Epidemiology; Gender; HIV; HIV Infections; HIV Seropositivity; HIV/HCV; Health Disparities Research; Hepatitis C; Hepatitis C Acquisition; Hepatitis C Incidence; Hepatitis C co-infection; Hepatitis C virus; Human; In Vitro; Individual; Infection; Inflammation; Longitudinal Studies; Minority; Minority Groups; Modeling; Molecular; Morbidity - disease rate; Neighborhood Health Center; Patients; Persons; Play; Prevalence; Primary Health Care; Public Health; Publishing; Recreational Drugs; Relapse; Research; Retrospective cohort; Risk Factors; Role; Route; Sexually Transmitted Diseases; Source; Testing; Tissues; Underrepresented Minority; Universities; Viral; Viremia; Virus; antiretroviral therapy; base; black men who have sex with men; chemokine; co-infection; cohort; comorbidity; cytokine; disparities in morbidity; exosome; health disparity; high risk population; immune activation; in vitro Model; innovation; macrophage; men; men who have sex with men; metropolitan; monocyte; mortality; mortality disparity; multiple drug use; pathogenic virus; socioeconomics; study population; syndemic; transgender women; transmission process; trend; uptake; urban health disparities

PROJECT SUMMARY Hepatitis C virus (HCV) and HIV are two chronic viral pathogens that disproportionately affect people of racial, gender, and socioeconomic minorities. The proposed studies aim to use a multi-pronged approach to study HCV, HIV and their co-infection, with epidemiologic, clinical, and basic science components. To study HCV coinfection in HIV-infected individuals, we have established a cohort of 1985 HIV-infected men receiving care at a multisite community health center in Metropolitan Baltimore. The study cohort encompasses various underrepresented minority groups. A large database with >85 variables has been built and quality-verified based on these patients. We have studied HCV incidence in this cohort and found a resurgence of incident HCV among men who have sex with men (MSM) since 2010, which was associated with polydrug use and co- occurrence of other sexually transmitted infections (STIs). One aim of this project is to perform further analyses using the existing database to achieve more discoveries and publishable findings. We propose to analyze the trends and risk factors of prevalent HCV, chronic HCV cascade of care and treatment uptake, and factors associated with spontaneous HCV clearance among the HIV-infected men. We will also analyze the syndemic of HCV, other STIs, and polydrug use among the HIV-infected MSM. Some minorities, such as African American MSM, transgender women, and residents of certain zip codes will be studied separately. The other aim of the project is to employ a unique model system of long-term culture (> 3 months) of primary human macrophages developed in our lab to study HIV latency and reactivation in these cellular reservoirs. Tissue macrophages have recently been shown to be the major “sanctuary” for HIV in the presence of antiretroviral treatment. Thus, a consistent and stable ex vivo and in vitro model to study long-term interactions between HIV and macrophages will be of great utility in the effort toward an HIV cure. In addition, HIV-induced chronic inflammation remains elevated in patients with undetectable viremia. Thus, we will test the hypothesis that macrophage reservoirs persistently infected with HIV play a role in enhancing and sustaining HIV-induced chronic immune activation through viral relapse and/or secreting virally modified exosomes. The results from this project will have important impact on the public health effort toward the eradication of these two important viral pathogens. 1

项目总结 丙型肝炎病毒和艾滋病毒是两种慢性病毒病原体，对不同种族的人影响不成比例， 性别和社会经济上的少数群体。建议的研究旨在多管齐下地研究 丙型肝炎病毒、艾滋病毒及其混合感染，包括流行病学、临床和基础科学组成部分。研究丙型肝炎病毒 在艾滋病毒感染者中合并感染，我们已经建立了1985名艾滋病毒感染者接受护理的队列 在巴尔的摩大都会的一家多地点社区卫生中心。这项研究队列涵盖了不同的 少数群体的代表性不足。建立了一个包含85个变量的大型数据库，并进行了质量验证 根据这些病人。我们研究了这个队列中丙型肝炎病毒的发病率，发现事件的死灰复燃 自2010年以来，男男性行为者(MSM)中的丙型肝炎病毒感染情况，这与多药使用和性接触有关 其他性传播感染(STI)的发生。该项目的一个目标是进行进一步的分析 利用现有的数据库实现更多的发现和可发布的发现。我们建议分析 丙型肝炎病毒流行的趋势和危险因素，慢性丙型肝炎病毒的护理和治疗吸收的级联，以及因素 与HIV感染男性中自发的丙型肝炎病毒清除有关。我们还将分析SYDEMIC 感染艾滋病毒的男男性接触者中的丙型肝炎病毒感染、其他性传播感染和多药使用情况。一些少数民族，如非洲人 美国MSM、跨性别女性和某些邮政编码地区的居民将被单独研究。另一个 该项目的目标是采用一种独特的原始人长期培养(&gt；3个月)的模型系统 我们实验室开发的巨噬细胞是为了研究HIV在这些细胞储存库中的潜伏和重新激活。组织 巨噬细胞最近被证明是艾滋病毒的主要“庇护所”，因为存在抗逆转录病毒药物。 治疗。因此，一个一致和稳定的体外和体外模型来研究艾滋病毒之间的长期相互作用 巨噬细胞将在治愈艾滋病毒的努力中发挥巨大作用。此外，艾滋病毒引发的慢性 在无法检测到的病毒血症患者中，炎症反应仍然很高。因此，我们将检验这一假设 持续感染HIV的巨噬细胞储存库在增强和维持HIV诱导的作用中发挥作用 通过病毒复发和/或分泌病毒修饰的外切体的慢性免疫激活。结果来自于 该项目将对公共卫生努力消除这两个重要因素产生重要影响 病毒病原体。 1