Alcohol's impact on immunological and virological profiles in HIV patients

酒精对艾滋病毒患者免疫学和病毒学特征的影响

基本信息

批准号：
9408187
负责人：
Qigui Q Yu
金额：
$ 15.28万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9408187
关键词：
Adherence Alcohol abuse Alcoholic Hepatitis Alcoholic Liver Diseases Alcoholic beverage heavy drinker Alcohols Bacterial Translocation Basic Science Blood Blood specimen Cell physiology Cells Characteristics Chronic Clinical Clinical Research Collection Comorbidity Controlled Study Cross-Sectional Studies DNA DNA Integration Data Development Disease Outcome Disease Progression Drug resistance Enrollment Gastrointestinal tract structure General Population HIV HIV Infections HIV therapy Health Immune Immune Cell Activation Immunologic Markers Immunologics Individual Inflammation Inflammatory International Investigation Lipopolysaccharides Liver Longitudinal Studies Observational Study Outcome Participant Pathogenesis Patients Peripheral Blood Mononuclear Cell Phase Phenotype Plasma Public Domains Public Health RNA Recombinant DNA Recruitment Activity Research Research Infrastructure Research Project Grants Resources Scientist T-Lymphocyte Target Populations Translational Research Viral Load result Virus Integration Virus Replication alcohol abstinence alcohol effect antiretroviral therapy chemokine cytokine design follow-up immune activation innovation longitudinal analysis microbial novel marker novel therapeutics prospective repository treatment response virology

项目摘要

Abstract Alcohol overconsumption and HIV infection are both major health issues worldwide. Alcohol abuse is more prevalent among HIV-infected people than the general population and strongly associated with poor adherence to antiretroviral therapy (ART) and poor treatment response, leading to HIV progression and ART drug resistance. More drastically, alcohol overconsumption and HIV infection independently damage the gastrointestinal (GI) tract mucosal barrier, leading to a leaky gut that allows microbial translocation (MT) and accumulation of microbial components such as lipopolysaccharide (LPS) in the blood. In HIV patients, MT is a cause of chronic immune activation and inflammation, which is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load. We hypothesize that alcohol overconsumption and HIV infection exacerbate MT, immune activation, inflammation, and viral replication, thereby accelerating disease progression of HIV infection and alcoholic liver disease such as alcoholic hepatitis (AH). We also hypothesize that alcohol abstinence slows or reverses immunological and virological impacts in HIV-infected heavy drinkers. We have formed a research team consisting of six scientists with complementary expertise in basic, translational, and clinical research of AH and HIV immunopathogenesis to undertake paradigm-changing investigations in the field of alcohol abuse in HIV patients (Aim 1, UH2 phase). We will enroll HIV-infected heavy drinkers and controls for studying alcohol's impact on HIV-associated comorbidities (Aim 2, UH2 phase). Participants recruited in the UH2 phase will be followed up every 6-month for a year for UH3 phase longitudinal analysis (Aim 3). The UH3 phase will also recruit and follow up new participants to perform a longitudinal analysis of alcohol's impact on MT, immune cell activation, inflammation, and viral replication and integration in HIV-infected heavy drinkers with or without AH (UH3 Phase). Our proposal is highly innovative and will greatly aid in developing novel biomarkers and therapies of HIV-infected heavy drinkers. The biosample repository, upon its placement in the public domain, will become a significant resource for facilitating national and international investigations of alcohol and HIV interactions.

抽象的酗酒和艾滋病毒感染都是世界范围内的主要健康问题。艾滋病毒感染者中酗酒的现象比一般人群更为普遍，与抗逆转录病毒治疗 (ART) 依从性差和治疗效果不佳密切相关反应，导致 HIV 进展和 ART 耐药性。更严重的是，酒精过度消费和 HIV 感染会独立损害胃肠道 (GI) 粘膜屏障，导致肠道渗漏，导致微生物移位 (MT) 和血液中脂多糖（LPS）等微生物成分的积累。在艾滋病毒中对于患者来说，MT 是慢性免疫激活和炎症的一个原因，这是慢性免疫激活和炎症的一个标志进行性 HIV 感染，比血浆病毒载量更好地预测疾病结果。我们假设过量饮酒和 HIV 感染会加剧 MT、免疫激活、炎症和病毒复制，从而加速 HIV 疾病进展感染和酒精性肝病，例如酒精性肝炎（AH）。我们还假设戒酒可减缓或逆转艾滋病毒感染者的免疫学和病毒学影响酗酒者。我们组建了一个由六位科学家组成的研究团队 AH 和 HIV 基础、转化和临床研究方面的互补专业知识免疫发病机制在酒精领域进行范式改变的研究 HIV 患者中的滥用（目标 1，UH2 阶段）。我们将招募感染艾滋病毒的重度饮酒者用于研究酒精对 HIV 相关合并症影响的对照（目标 2，UH2 阶段）。 UH2 阶段招募的参与者将在 UH3 阶段每 6 个月进行一次随访，为期一年相纵向分析（目标 3）。 UH3阶段还将招募并跟进新人参与者对酒精对 MT、免疫细胞激活的影响进行纵向分析，感染艾滋病毒的重度饮酒者的炎症、病毒复制和整合有或没有 AH（UH3 阶段）。我们的建议具有高度创新性，将极大地帮助开发新颖的感染艾滋病毒的重度饮酒者的生物标志物和治疗。生物样本库，根据其置于公共领域，将成为促进国家和地区的重要资源关于酒精和艾滋病毒相互作用的国际调查。