Immune Dys-regulation in HIV-infected women with heavy alcohol consumption

大量饮酒的艾滋病毒感染妇女的免疫失调

• 批准号: 8211451
• 负责人: Seema Desai
• 金额: $ 37.24万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-10 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8211451
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adherence; Affect; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Behavioral; Behavioral Mechanisms; Blood Circulation; CD28 gene; CD4 Positive T Lymphocytes; CD8B1 gene; Caring; Chronic; Clinical; Comorbidity; Databases; Discipline; Disease; Disease Progression; Environment; Environmental Risk Factor; Epidemiologist; Event; Failure; Future; HIV; HIV therapy; Harm Reduction; Health; Highly Active Antiretroviral Therapy; Immune; Immune System Diseases; Immune system; Immunologic Markers; Immunologics; Immunologist; Individual; Inflammation; Interleukin-6; Intervention; Intestines; Link; Measures; Mediating; Microbe; Modality; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Outcome; Pathway interactions; Permeability; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Probiotics; Randomized Clinical Trials; Regulation; Reporting; Research; Risk; Scientist; Specimen; Staging; T-Lymphocyte; TNF gene; Testing; Viral Load result; Woman; alcohol exposure; alcohol measurement; biobank; chronic alcohol ingestion; cohort; drinking; hazardous drinking; immune activation; improved; microbial; mortality; outcome forecast; randomized trial; repository; senescence; therapy adherence; translational study

DESCRIPTION (provided by applicant): Alcohol consumption is common in HIV infected individuals and heavy alcohol consumption has been associated with accelerated HIV disease progression and poor health outcomes. This proposal will investigate mechanism underlying CD4 T cell decline and HIV disease progression in HIV infected women who engage in heavy alcohol consumption. One mechanism by which alcohol may cause immune dysfunction is by inducing microbial translocation. We will examine whether chronic cumulative exposure (amount x duration) over 10 years of observation period is associated with more rapid CD4 T cell decline and immune dysfunctionality namely exacerbation in levels of immune activation, inflammation and immune senescence leading to early advent of AIDS and Non AIDS co-morbidities. We will test our hypothesis that heavy alcohol consumption, defined using NIAAA criteria for hazardous drinking (for women, >7drinks/week or >3 drinks per occasion), disrupts the gut barrier causing microbial translocation which enhances systemic immune activation, inflammation and senescence; all events that contribute to CD4 T-cell decline and HIV disease progression. We will conduct this study retrospectively in bioreposited specimens from the longitudinal cohort, the Women's Interagency HIV Study. As a secondary aim linked to the other UO-1 in this consortium; a randomized clinical trial on alcohol reduction medication naltrexone, we will examine in subset of HIV infected heavy drinkers, whether alcohol reduction medication, naltrexone improves alcohol related immune dysregulation. We will create a repository and database of immune markers (translocation, immune activation, inflammation, and immune senescence) in HIV infected women who engage in hazardous drinking; which can be used for future translational studies related to alcohol and HIV interaction: observational or mechanistic. This project has a cross discipline expertise, from leading clinicians in the HIV/AIDS field, behavioral scientists, epidemiologist, and immunologist for successful implementation of the aims and objectives of this study. PUBLIC HEALTH RELEVANCE: Should microbial translocation prove to be the detrimental pathway due to chronic alcohol use, this research will give leads to developing new modalities to improve gut environment. The results of this study will lay emphasis on behavioral mechanisms such as alcohol use that could be a contributing to the unresolved problem of activation/inflammation and non AIDS defining co-morbidities despite effective HAART.

描述（由申请人提供）：饮酒在艾滋病毒感染的个体中很常见，大量饮酒与加速HIV疾病进展和健康状况不佳有关。该提案将调查CD4 T细胞下降和HIV疾病进展的机制，这些艾滋病毒感染的妇女从事大量饮酒。酒精可能引起免疫功能障碍的一种机制是诱导微生物易位。我们将检查10年的慢性累积暴露（数量X持续时间）是否与更快的CD4 T细胞下降和免疫功能障碍有关，即在免疫激活，炎症和免疫衰老水平上加剧，导致艾滋病和非助剂的早期出现。我们将检验我们的假设，即使用NIAAA危险饮酒的NIAAA标准定义的大量饮酒（对于女性，每周> 7drinks或每次饮料> 3次饮料），破坏了肠道障碍，导致微生物易位，从而增强了系统性免疫激活，炎症，炎症和衰老；所有导致CD4 T细胞下降和HIV疾病进展的事件。我们将在纵向队列妇女间艾滋病毒研究的纵向同类群体中回顾性地进行这项研究。作为与该财团中的另一个UO-1相关的次要目标；一项关于降低酒精药物纳曲酮的随机临床试验，我们将在HIV感染的重型饮酒者的子集中检查，无论酒精降低药物，Naltrexone是否可以改善与酒精相关的免疫失调。我们将在艾滋病毒感染危险饮酒的艾滋病毒感染妇女中创建一个免疫标记，免疫激活，炎症和免疫衰老的存储库和数据库；可用于与酒精和HIV相互作用有关的未来翻译研究：观察性或机械性。该项目具有跨学科专业知识，从艾滋病毒/艾滋病领域的领先临床医生，行为科学家，流行病学家和免疫学家成功实施了这项研究的目标和目标。 公共卫生相关性：如果由于长期使用酒精饮酒，微生物易位应被证明是有害的途径，这项研究将导致开发新的方式以改善肠道环境。这项研究的结果将重点放在诸如饮酒之类的行为机制上，这可能是导致尚未解决的激活/炎症问题，尽管有效HAART，但仍定义了合并症的非AIDS。