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着降低了艾滋病毒相关死亡率，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跟踪现有的迈阿密艾滋病毒成人研究（MASH）队列、其标本储存库和数据库，并将其从目前的881名研究参与者扩大到1,500名。其目的是产生合作研究，调查可卡因的影响，到目前为止，最流行的药物滥用在南佛罗里达，对艾滋病毒感染，艾滋病毒/丙型肝炎病毒合并感染，并对长期发病率，重点是肝脏疾病在这一人群中的差异，获得护理。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。随着新的和更有效的治疗和获得艾滋病毒，丙型肝炎病毒和药物滥用的护理变得可用，保持一个良好的特征化的队列，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。观察新的HCV治疗和潜在的新的可卡因戒断计划在这一健康差异的高危人群的吸收将提供有效治疗的障碍和促进因素的数据，以防止长期发病率和死亡率。我们对881名参与者的MASH队列进行了长达12年的随访，保留率非常高，并创建了一个标本库和数据库。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，有大量的非裔美国人、女性、非注射器吸毒者，主要是异性恋的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），比较可卡因使用者和非使用者中HIV+/HCV-、HIV+/HCV+、HIV-/HCV+和HIV-/HCV-在4年内的肝纤维化进展。我们还建议（2）比较四年来生物标志物的模式，并确定可卡因使用者和非使用者之间与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合并感染背景下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，并为确定抗纤维化疗法（如氧化应激）提供基础，这些疗法适合干预。这些研究对于项目开发、适当的干预措施和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.