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

项目摘要 丙型肝炎病毒（HCV）和艾滋病毒是两种慢性病毒病原体， 性别和社会经济少数群体。建议的研究旨在采用多管齐下的方法研究 HCV、HIV及其合并感染，包括流行病学、临床和基础科学组成部分。研究HCV 在艾滋病毒感染者的合并感染，我们已经建立了一个队列的1985名艾滋病毒感染的男子接受护理 在大都会巴尔的摩的多点社区健康中心。研究队列包括各种 代表性不足的少数群体。已建立了一个包含>85个变量的大型数据库，并进行了质量验证 基于这些患者。我们研究了这一队列中的HCV发病率， 自2010年以来，与男性发生性关系的男性（MSM）中的HCV与多种药物的使用和共同使用有关。 发生其他性传播感染（STI）。该项目的一个目的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验证的发现。我们建议分析 流行HCV的趋势和风险因素，慢性HCV级联护理和治疗的吸收，以及因素 与HIV感染者中HCV的自发清除有关。我们还将分析 HIV感染的MSM人群中HCV、其他性传播感染和多种药物的使用。一些少数民族，如非洲人 美国男男性接触者、跨性别女性和某些邮政编码的居民将分别进行研究。另 该项目的目的是采用一个独特的模型系统，长期培养（> 3个月）的初级人类 在我们的实验室开发的巨噬细胞研究艾滋病毒潜伏期和这些细胞库中的再激活。组织 巨噬细胞最近被证明是HIV在抗逆转录病毒药物存在下的主要“避难所 治疗因此，一个一致的和稳定的离体和体外模型，以研究艾滋病毒之间的长期相互作用， 巨噬细胞将在艾滋病治疗中发挥巨大作用。此外，艾滋病毒引起的慢性 在病毒血症检测不到的患者中，炎症仍然升高。因此，我们将测试假设， 持续感染HIV的巨噬细胞储库在增强和维持HIV诱导的 通过病毒复发和/或分泌病毒修饰的外来体的慢性免疫激活。的结果 该项目将对公共卫生工作产生重要影响， 病毒病原体 1

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