Translational Research on Alcohol, Immunodeficiency, and Aging In COMpAAAS

描述（由申请人提供）：联合抗逆转录病毒疗法（cART）已将艾滋病毒转化为一种复杂的慢性疾病，但并不能完全恢复健康。虽然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、饮酒和多重发病。即使HIV感染受到抑制，它也与免疫系统的慢性激活有关。酒精使用和多重发病在老年HIV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、酒精使用、由艾滋病毒和多种疾病引起的多重发病和多重用药可造成直接的器官系统损伤。为了更好地理解这一过程，我们建议从退伍军人老龄化队列研究中招募200名HIV感染的cART（和抗逆转录病毒）新手和100名未感染的个体（HIV-）。我们的具体目标是：(1)在启动cART的HIV+个体和人口统计学和行为相似的未感染比较者中收集和储存一系列生物标本样本，并开始使用这些样本来表征(2)酒精使用和免疫功能多重发病的纵向关联(3)酒精使用和多重用药对器官系统损伤的影响（通过VACS指数及其组成部分测量）。在艾滋病毒阳性者中，我们将在开始cART之前和之后收集标本。我们假设酒精、多重发病、多重用药和免疫功能障碍将存在于两组的所有年龄组中，并且酒精、多重发病和多重用药将与免疫功能障碍和终末器官损伤的增加有关。酒精使用将通过自我报告和磷脂酰乙醇来评估。如果我们要了解艾滋病毒感染者的衰老和饮酒情况与未感染的类似比较者的衰老和饮酒情况有何不同，这些目标至关重要。这项工作将有助于描述饮酒老年人的免疫功能障碍和器官系统损伤。最后，这些纵向标本可以与HIV+和人口统计学和行为相似的未感染者的临床结果和亚临床疾病测量相关联，为VACS社区内外的研究人员提供独特而有价值的资源。

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.