Cohort Studies on HIV/AIDS and Substance Abuse in Miami

描述（由申请人提供）：肝病是美国HIV感染者死亡的主要原因。虽然抗逆转录病毒治疗的进展显著降低了艾滋病毒相关的死亡率，但丙型肝炎病毒（HCV）的合并感染很普遍，并加速了肝纤维化向肝硬化和肝癌的进展。此外，药物滥用加速HIV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遵循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名扩展到1500名研究参与者。其目的是开展合作研究，调查可卡因对艾滋病毒感染、艾滋病毒/丙型肝炎病毒合并感染以及长期发病率的影响，重点关注在获得护理方面存在差异的人群中的肝病。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，以便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/丙型肝炎病毒合并感染的相互作用。随着艾滋病毒、丙型肝炎病毒和药物滥用的新的和更有效的治疗方法和护理的出现，保持一个特征良好的队列、标本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。在这些存在健康差异的高危人群中观察新的丙型肝炎治疗方法和潜在的新的可卡因戒烟计划的采用情况，将为有效治疗预防长期发病率和死亡率的障碍和促进因素提供数据。我们对881名MASH参与者进行了长达12年的跟踪，保留率很高，并建立了标本库和数据库。迈阿密的MASH队列是独特的，因为它将是一个主要是西班牙裔的队列，其中有大量的非洲裔美国人，妇女，非注射吸毒者，主要是异性恋HIV传播病因。我们建议(1)使用一种新型的非侵入性诊断设备磁共振弹性成像（MRE），比较在HIV+/HCV-、HIV+/HCV+、HIV-/HCV+和HIV-/HCV-中，可卡因使用者和非使用者在四年中的肝纤维化进展。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/丙型肝炎合并感染中的作用以及可卡因使用停止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局，并为确定可干预的抗纤维化疗法（如氧化应激）提供基础。这些研究将是至关重要的项目发展，适当的干预措施，并为改善这一人群的健康。

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.