2/3 COMpAAAS Tripartite: ART-CC, KP, and VA

项目概要/摘要 饮酒的艾滋病毒成年人由于艾滋病毒感染、合并症（包括丙型肝炎）而生理上已经很虚弱 感染）、复方用药和相关物质使用。在这种情况下，酒精的生物医学后果 适度使用可能会导致使用，并且经常不被重视或被错误归因。 “改善联盟” “艾滋病毒/艾滋病、酒精、衰老和多种物质的结果”(COMpAAAS) 得到 NIH/NIAAA 奖的支持 U24AA020794 在单个样本中研究这个问题，即退伍军人老龄化队列研究 (VACS)（约 50,000 HIV 美国退伍军人在人口统计上与约 100,000 名未感染的对照者相匹配）。 VACS 将直接聘用 酒精生物标志物（磷脂酰乙醇 [PEth] 和经过验证的生理虚弱指标（VACS 指数）。 这组三个应用程序，抗逆转录病毒治疗队列协作 (ART-CC) 和 Kaiser Permanente (KP) 团队作为 COMpAAAS 三方加入退伍军人医疗保健系统 (VA) 团队：ART-CC、 KP 和 VA。我们的长期目标是为酒精干预措施的设计和实施提供信息。我们一起 提议研究酒精和相关物质使用对艾滋病毒的生物医学影响，扩大 VACS 对北美和欧洲多个医疗保健系统的范围和普遍性 大幅增加艾滋病毒受试者的样本量和多样性。重要的是，COMpAAAS 三方还 扩大了未感染的比较者的样本，如果我们要了解酒精如何影响，这是一个至关重要的群体 对艾滋病毒的生物医学结果有不同的影响。 KP 将能够识别人口统计匹配的 来自北加州地区未感染的对照者。 1945-1965 年出生的退伍军人的新 VA 样本 （出生队列）扩大了丙型肝炎感染者 (HCV) 和女性对照者的接触范围。三方组 还将参加 HIV 亚研究 (n=2250)，HIV 研究中的药物、酒精、物质使用 （MASH），其中关于潜在不适当药物（PIMS）和酒精和酒精生物标志物的新数据 将收集物质（烟草、大麻、阿片类药物、可卡因和甲基苯丙胺）。作为主导站点 对于目标 2，KP 将研究酒精和吸烟对艾滋病毒结果、预防保健和医疗的影响 合并症。我们预计，在艾滋病毒感染者中，危险性饮酒、酒精使用障碍和 吸烟会对这些结果产生负面影响；这些影响在艾滋病毒中会被放大 个体与未感染个体的比较。最初，分析将使用电子健康记录数据 包括自我报告的酒精和药物使用情况。分析将在最后一年重复进行，以纠正 根据 MASH 结果，自我报告的酒精和药物使用存在偏差。与 RFA 一致，所有 赠款为所有目标提供数据，具有相同的目标和协议。该应用程序解决了关键 饮酒和吸烟、抗逆转录病毒药物和可能增加死亡率的药物之间的相互作用， 住院、虚弱并对预防性医疗保健产生不利影响。我们预计调查结果可能会导致 创新干预措施的发展，例如结合酒精、吸烟和预防保健干预措施。

PROJECT SUMMARY/ABSTRACT HIV+ adults who drink are already physiologically frail due to HIV infection, comorbidity (including hepatitis C infection), polypharmacy and associated substance use. In this setting, biomedical consequences of alcohol use can occur with moderate use and are often unappreciated or misattributed. The “Consortium to improve OutcoMes in HIV/Aids, Alcohol, Aging & multi-Substance” (COMpAAAS) is supported by NIH/NIAAA award U24AA020794 to study this issue in a single sample, the Veterans Aging Cohort Study (VACS) (~50,000 HIV+ US veterans demographically matched to ~100,000 uninfected comparators). VACS will employ a direct alcohol biomarker (Phosphatidyl-ethanol [PEth] and a validated measure of physiologic frailty (VACS Index). In this set of three applications, the Antiretroviral Therapy Cohort Collaboration (ART-CC) and Kaiser Permanente (KP) teams join the Veterans Healthcare System (VA) team as COMpAAAS Tripartite: ART-CC, KP, and VA. Our long term goal is to inform alcohol intervention design and implementation. Together we propose to study biomedical consequences of alcohol and associated substance use in HIV, extending the scope and generalizability of VACS to multiple healthcare systems in North America and Europe and substantially increasing sample size and diversity of HIV+ subjects. Importantly, COMpAAAS Tripartite also expands the sample of uninfected comparators, a critically important group if we are to understand how alcohol differentially affects biomedical outcomes in HIV. KP will be able to identify demographically-matched uninfected comparators from their Northern California region. A new VA sample of veterans born in 1945-1965 (Birth Cohort) expands access to Hepatitis C infected (HCV+) and women comparators. The tripartite group will also participate in an HIV+ substudy (n=2250), The Medications, Alcohol, Substance Use in HIV Study (MASH), in which new data on potentially inappropriate medications (PIMS) and biomarkers for alcohol and substances (tobacco, marijuana, opioids, cocaine, and methamphetamine) will be collected. As the lead site for Aim 2, KP will examine the impact of alcohol and smoking on HIV outcomes, preventive care, and medical comorbidities. We anticipate that among HIV+ individuals, hazardous alcohol use, alcohol use disorders and smoking will negatively impact each of these outcomes; and that these effects will be amplified in HIV+ individuals compared with uninfected individuals. Initially, analyses will use electronic health record data including self-reported alcohol and substance use. Analyses will be repeated in the final year correcting for biases in self-reported alcohol and substance use based upon MASH results. Consistent with the RFA, all grants contribute data for all aims, have identical aims and protocols. This application addresses key interactions between alcohol and tobacco use, antiretrovirals, and medications that may increase mortality, hospitalization, frailty, and adversely impact preventive health care. We anticipate findings may lead to innovative intervention development, such as combined alcohol, smoking and preventive care interventions.