Translational Research on Alcohol, Immunodeficiency, and Aging In COMpAAAS

描述(申请人提供)：联合抗逆转录病毒疗法(CART)已经将艾滋病毒转变为一种复杂的慢性病，但并不能完全恢复健康。尽管这一事实的原因尚不清楚，但可能的原因包括慢性免疫激活、酗酒和多发病。即使艾滋病毒感染被抑制，它也与免疫系统的慢性激活有关。酗酒和多发病在老年艾滋病毒感染者(HIV+)中很常见，它们会导致免疫激活。慢性免疫激活与免疫功能障碍、器官系统损伤和死亡有关。艾滋病毒、酗酒、多种疾病以及由艾滋病毒和多种疾病引起的多种药物可导致直接的器官系统损伤。为了更好地了解这一过程，我们建议从退伍军人老龄化队列研究中招募200名感染艾滋病毒的CART(和抗逆转录病毒)天真的人和100名未感染艾滋病毒的人(HIV-)。我们的具体目标是(1)收集和储存启动CART的HIV+个体以及人口和行为相似的未感染对照人群的连续生物样本，并开始使用这些样本来表征(2)酒精使用和多发病对免疫功能的纵向关联；(3)酒精使用和多药对器官系统损伤的VAS指数及其组成部分的衡量。在HIV+人群中，我们将在CART开始之前和之后收集样本。我们假设酒精、多种疾病、多种药物和免疫功能障碍将出现在两组的所有年龄组中，酒精、多种疾病和多种药物将与增加的免疫功能障碍和终末器官损害相关。酒精使用情况将通过自我报告和磷脂酰乙醇进行评估。如果我们想要了解在未感染的相似对照中，老龄化和饮酒与老龄化和饮酒有何不同，这些目标是至关重要的。这项工作将有助于确定饮酒老年人的免疫功能障碍和器官系统损伤的特征。最后，这些纵向标本可以与艾滋病毒阳性和在人口统计学和行为上相似的未感染人群中判定的临床结果和亚临床疾病措施联系起来，为真空吸毒者社区内外的研究人员提供独特和宝贵的资源。

DESCRIPTION (provided by applicant): Combination antiretroviral therapy (cART) has transformed HIV into a complex chronic disease but does not fully restore health. Although the reasons for this fact are not clear, likely causes include chronic immune activation, alcohol use, and multimorbidity. Even when HIV infection is suppressed, it is associated with chronic activation of the immune system. Alcohol use and multimorbidity are common among those aging with HIV infection (HIV+) and they lead to immune activation. Chronic immune activation is associated with immune dysfunction, organ system injury, and death. HIV, alcohol use, multimorbidity and polypharmacy resulting from HIV and multimorbidity can cause direct organ system injury. To better understand this process we propose to enroll 200 HIV infected cART (and antiretroviral) naive individuals and 100 uninfected individuals (HIV-) from the Veterans Aging Cohort Study. Our specific aims are to (1) collect and bank serial biospecimen samples among HIV+ individuals initiating cART and demographically and behaviorally similar uninfected comparators and to begin to use these samples to characterize (2) the longitudinal associations of alcohol use and multimorbidity on immune function and (3) alcohol use and polypharmacy on organ system injury as measured by the VACS index and its components. Among HIV+ we will collect specimens before and after cART initiation. We hypothesize that alcohol, multimorbidity, polypharmacy and immune dysfunction will be present in all age groups of both groups and that alcohol, multimorbidity, and polypharmacy will be associated with increasing immune dysfunction and end organ damage. Alcohol use will be assessed by self-report and phosphatidyl ethanol. These aims are critical if we are to understand how aging and alcohol use with HIV differs from aging and alcohol use among uninfected similar comparators. This work will help characterize immune dysfunction and organ system injury among aging individuals who drink alcohol. Lastly, these longitudinal specimens can be linked with adjudicated clinical outcomes and subclinical disease measures among HIV+ and demographically and behaviorally similar uninfected people to provide a unique and valuable resource for investigators within and outside the VACS community.