Cohort Studies on HIV/AIDS and Substance Abuse in Miami

 描述(申请人提供)：肝病是美国艾滋病毒感染者的主要死因。虽然抗逆转录病毒治疗的进展显著降低了艾滋病毒相关死亡率，但与丙型肝炎病毒(HCV)的混合感染普遍存在，并加速了肝纤维化向肝硬变和肝癌的进展。此外，药物滥用会加速HIV疾病，并可能促进肝纤维化的进展。这项提议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、其标本库和数据库，并将其从目前的881名研究参与者扩大到1500名参与者。其目的是开展合作研究，以调查可卡因对艾滋病毒感染、艾滋病毒/丙型肝炎病毒混合感染以及长期发病率的影响，重点是在获得护理的机会存在差异的这一人群中，肝脏疾病。可卡因是南佛罗里达州迄今为止最普遍的滥用药物。还将招募未感染艾滋病毒和丙型肝炎病毒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，以及可卡因使用与艾滋病毒、丙型肝炎病毒和艾滋病毒/丙型肝炎病毒共同感染的相互作用。随着针对艾滋病毒、丙型肝炎病毒和药物滥用的新的、更有效的治疗和护理的出现，维持一个特征良好的队列、标本储存库和数据库将为当前和未来的合作研究创造一个强大的资源平台。观察新的丙型肝炎病毒治疗方法和潜在的新的可卡因戒断计划在这一具有健康差异的高危人群中的接受情况，将提供有关有效治疗的障碍和促进者的数据，以防止长期发病率和死亡率。我们已经跟踪了881名参与者长达12年的MASH队列，并保持了出色的保留率，并创建了一个标本储存库和一个数据库。迈阿密的MASH队列是独一无二的，因为它将是一个以西班牙裔为主的队列，其中有大量非裔美国人、女性、非注射吸毒者，他们主要是异性恋艾滋病毒传播病因。我们建议(1)使用一种新的非侵入性诊断设备，磁共振弹性成像(MRE)，比较HIV+/丙型肝炎病毒(HIV+/丙型肝炎病毒)、HIV+/丙型肝炎病毒(HIV+/丙型肝炎病毒+)、HIV-/丙型肝炎病毒+(HIV-/丙型肝炎病毒+)可卡因吸毒者和非吸毒者四年来肝纤维化的进展情况。我们还建议(2)比较四年来生物标志物的模式，并确定与可卡因使用者和非使用者之间的肝纤维化机制相关的遗传标记。了解可卡因使用在艾滋病毒和艾滋病毒/丙型肝炎病毒混合感染中的作用以及缺乏戒除可卡因使用治疗的持久影响至关重要，以便深入了解发病机制和疾病后果，并为确定氧化应激等可干预的抗纤维化疗法提供基础。这些研究对于规划开发、适当的干预措施以及改善这一人群的健康状况至关重要。

 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.