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

描述（由申请人提供）：饮酒在HIV感染者中很常见，大量饮酒与加速HIV疾病进展和不良健康结局相关。该提案将调查参与大量饮酒的HIV感染妇女的CD 4 T细胞下降和HIV疾病进展的潜在机制。酒精可能导致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年观察期内的慢性累积暴露（量x持续时间）是否与更快的CD 4 T细胞下降和免疫功能障碍（即免疫激活、炎症和免疫衰老水平的恶化，导致艾滋病和非艾滋病合并症的早期出现）相关。我们将测试我们的假设，即使用NIAAA危险饮酒标准定义的大量饮酒（对于女性，每周> 7杯或每次>3杯），破坏肠道屏障，导致微生物易位，增强全身免疫激活，炎症和衰老;所有事件都有助于CD 4 T细胞下降和HIV疾病进展。我们将回顾性地进行这项研究，在纵向队列，妇女的跨部门艾滋病毒研究的生物定位标本。作为与该联盟中其他UO-1相关的次要目的;一项关于酒精减少药物纳曲酮的随机临床试验，我们将在HIV感染的重度饮酒者中检查酒精减少药物纳曲酮是否改善酒精相关的免疫失调。我们将在从事危险饮酒的HIV感染女性中创建免疫标记物（易位，免疫激活，炎症和免疫衰老）的存储库和数据库;可用于未来与酒精和HIV相互作用相关的转化研究：观察或机制。该项目具有跨学科的专业知识，来自艾滋病毒/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，以成功实现本研究的目的和目标。

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.