Cohort Studies on HIV/AIDS and Substance Abuse in Miami

迈阿密艾滋病毒/艾滋病和药物滥用队列研究

• 批准号: 9927614
• 负责人: Marianna K Baum
• 金额: $ 107.78万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927614
• 关键词: AIDS/HIV problem; Adult; African American; Alcohols; Animal Experiments; Animals; Apoptosis; Apoptotic; Area; Behavioral; Biological Markers; Biological Specimen Banks; Cause of Death; Cessation of life; Cirrhosis; Clinical; Cocaine; Cocaine Abuse; Cocaine Users; Cohort Studies; Data; Databases; Devices; Diagnostic; Disease; Disease Outcome; Drug abuse; Etiology; FDA approved; Florida; Funding; Future; Genetic Markers; Goals; HIV; HIV Infections; HIV/HCV; Health; Health Services Accessibility; Hepatitis C; Hepatitis C Therapy; Hepatitis C co-infection; Hepatitis C virus; Heterosexuals; Hispanics; Human; Immunity; Immunosuppression; In Vitro; Intervention; Laboratories; Liver Fibrosis; Liver diseases; Magnetic Resonance Elastography; Malnutrition; Metabolic; Morbidity - disease rate; Nature; Outcome; Oxidative Stress; Participant; Pathogenesis; Pattern; Persons; Pharmaceutical Preparations; Pharmacotherapy; Population; Populations at Risk; Primary carcinoma of the liver cells; Prognostic Factor; Program Development; Program Evaluation; Quality of life; Recording of previous events; Research; Research Design; Resources; Risk Factors; Role; Signal Transduction; Stimulus; Substance abuse problem; Treatment Failure; United States; United States National Institutes of Health; Virus Diseases; Woman; antiretroviral therapy; chronic liver disease; co-infection; cocaine use; cohort; comorbidity; cytokine; data harmonization; drug of abuse; effective intervention; effective therapy; evidence base; fibrogenesis; follow-up; health care availability; health disparity; improved; insight; interest; liver development; mortality; noninvasive diagnosis; novel; prevent; programs; prospective; public health relevance; recruit; retention rate; sociodemographics; time interval; transmission process; treatment effect; uptake

DESCRIPTION (provided by applicant): Liver disease is a major cause of death in HIV infected persons in the United States. While advances in antiretroviral therapy have significantly reduced HIV-related mortality, co-infection with hepatitis C virus (HCV), is widespread and accelerates progression of liver fibrosis to cirrhosis and liver carcinoma. In addition, substance abuse accelerates HIV disease, and may facilitate progression of liver fibrosis. The primary goal of this proposal is to continue to follow the existing Miami Adult Studies on HIV (MASH) cohort, its specimen repository and database, and expand it from the current 881 to 1,500 study participants. The purpose is to generate collaborative studies to investigate the impact of cocaine, by far the most prevalent drug of abuse in South Florida, on HIV infection, HIV/HCV co-infection, and on long-term morbidity with a focus on liver disease in this population with disparities in access to care. HIV and HCV un-infected cocaine users and non-users will also be recruited to allow determination of the impact of cocaine use alone, as well as the interaction of cocaine use with HIV, HCV, and HIV/HCV co-infection. As new and more effective treatments and access to care for HIV, HCV and drug abuse become available, maintaining a well- characterized cohort, specimen repository and database will create a strong resource platform for current and future collaborative research. Observing the uptake of new HCV treatments and potential new cocaine cessation programs in this at-risk population with health disparities will provide data on barriers and facilitators to effective treatments to prevent long-term morbidity and mortality. We have followed the MASH cohort of 881 participants for up to 12 years with excellent retention rates, and have created a specimen repository and a database. The MASH cohort in Miami is unique because it will be a mostly Hispanic cohort with a large number of African Americans, women, non-injector drug users, with predominantly heterosexual HIV- transmission etiology. We propose to (1) compare the progression of liver fibrosis over four years among cocaine users and non-users in HIV+/HCV-, HIV+/HCV+, HIV-/HCV+, and HIV-/HCV-, using a novel non- invasive diagnostic device, the Magnetic Resonance Elastography (MRE). We also propose to (2) compare the pattern over four years of biomarkers and identify genetic markers associated with the mechanisms of liver fibrosis among cocaine users and non-users. Understanding the role of cocaine use in the context of HIV and HIV/HCV co-infections and lack of lasting effects of treatments for cocaine use cessation are crucial in order to gain insights into the pathogenesis and disease outcomes, and to provide the basis for identifying antifibrotic therapies such as oxidative stress, which are amenable to intervention. These studies will be critical for program development, appropriate interventions, and for improving health in this population.

描述（由申请人提供）：肝病是美国艾滋病毒感染者死亡的主要原因。虽然抗逆转录病毒治疗的进步显着降低了艾滋病毒相关死亡率，但丙型肝炎病毒 (HCV) 合并感染很普遍，并加速肝纤维化进展为肝硬化和肝癌。此外，药物滥用会加速艾滋病毒疾病，并可能促进肝纤维化的进展。该提案的主要目标是继续跟踪现有的迈阿密成人艾滋病毒研究 (MASH) 队列、其样本库和数据库，并将其从目前的 881 名研究参与者扩大到 1,500 名研究参与者。目的是开展合作研究，调查可卡因（迄今为止南佛罗里达州最常见的滥用药物）对 HIV 感染、HIV/HCV 混合感染以及长期发病率（重点关注肝病）的影响。这些人群在获得护理方面存在差异。还将招募未感染 HIV 和 HCV 的可卡因使用者和非使用者，以确定单独使用可卡因的影响，以及可卡因使用与 HIV、HCV 和 HIV/HCV 合并感染的相互作用。随着针对艾滋病毒、丙型肝炎和药物滥用的新的、更有效的治疗方法和护理的出现，维护一个特征明确的队列、样本库和数据库将为当前和未来的合作研究创建一个强大的资源平台。观察这一存在健康差异的高危人群对新的丙型肝炎治疗方法和潜在的新的可卡因戒断计划的采用情况，将提供有关有效治疗的障碍和促进因素的数据，以预防长期发病率和死亡率。我们对 MASH 队列的 881 名参与者进行了长达 12 年的跟踪，保持率极高，并创建了样本库和数据库。迈阿密的 MASH 队列是独一无二的，因为它将主要是西班牙裔队列，其中有大量非裔美国人、女性、非注射吸毒者，主要具有异性恋艾滋病毒传播病因。我们建议 (1) 使用一种新型非侵入性方法，比较可卡因使用者和非使用者四年内 HIV+/HCV-、HIV+/HCV+、HIV-/HCV+ 和 HIV-/HCV- 的肝纤维化进展情况。诊断设备，磁共振弹性成像（MRE）。我们还建议（2）比较四年来的生物标志物模式，并确定与可卡因使用者和非使用者肝纤维化机制相关的遗传标志物。了解可卡因使用在 HIV 和 HIV/HCV 合并感染中的作用以及可卡因戒断治疗缺乏持久效果至关重要，以便深入了解发病机制和疾病结果，并为识别可卡因提供基础抗纤维化疗法，例如氧化应激，可以进行干预。这些研究对于计划的制定、适当的干预措施以及改善该人群的健康至关重要。