Effects of experimentally-induced reductions in alcohol consumption on brain cognitive, and clinical outcomes and motivation for changing drinking in older persons with HIV infection

这项拟议的U 01研究将建立在我们过去的发现，以确定在多大程度上显着减少， 通过应急管理（CM）在4周内饮酒可以改善认知能力，大脑 功能和病理生理学，以及艾滋病毒相关的健康结果。hiv相关神经认知 即使接受抗逆转录病毒治疗，功能障碍仍在继续，即使是轻度认知障碍也与 艾滋病毒阳性老年人的有害健康结果。饮酒可能会直接影响大脑， 间接通过肝毒性和全身炎症。我们过去的研究结果表明，目前大量饮酒 与终身消费相比，与艾滋病毒阳性成年人的认知/脑功能障碍更密切相关， 这表明这些影响可能随着饮酒量的减少而逆转。为了实现这一目标，我们建议 招募180名重度饮酒的HIV+成人，然后使用CM，并提供经济激励和可穿戴设备。 酒精生物传感器，从基线（T1）到4周后（T2）最大限度地减少酒精消耗。我们将 然后进行动机访谈，以确定减少饮酒的感知益处和障碍， 1年后（T3）进行最终评估，此时患者可能已恢复或可能未恢复重度 喝酒我们将在每个实验室进行最先进的神经成像、认知和行为评估。 时间点，然后继续跟踪我们的同伴队列（U24）的长期饮酒和艾滋病毒结果。 该提案的具体目的是：1）证明认知能力和大脑功能的改善 （fMRI）在CM诱导的HIV+成人酒精减少4周后， 如果大量饮酒恢复，1年后的影响; 2）证明脑代谢（MRS）和 神经炎症（无DTI水）标记物也将随着CM诱导的酒精减少而改善，如果 CM后饮酒恢复;以及3）确定减少饮酒的感知益处和挑战 在动机访谈（MI）中确定的预测CM后一年饮酒减少或复发。我们将 还确定脑病理生理学（MRS，DTI-FW）的变化是否与 认知、脑功能（fMRI）和血清炎症和肝脏生物标志物。此外，我们将确定 哪些神经影像学和基线临床因素与长期饮酒和临床结果相关 (e.g. HIV病毒抑制、肝脏合并症）。在这项研究的背景下，CM和MI被用作 实验操作和数据收集机会，而不是临床干预 本质上A-B-A设计将使我们能够清楚地识别酒精是否会影响认知和大脑 是可逆的，并确定最佳战略，以促进短期和长期减少艾滋病毒+酒精 成年人了该U 01项目与U24行政项目（SHARC）密切相关，后者支持佛罗里达 队列是本研究潜在参与者的来源，我们的行为科学和生物统计学 核心（U24），将有助于实施和监测CM，MI和酒精生物传感器程序。

This proposed U01 study will build on our past findings to determine the extent to which marked reductions in alcohol consumption over 4-weeks via contingency management (CM) improves cognitive performance, brain functions and pathophysiology, and HIV-associated health outcomes. HIV-associated neurocognitive dysfunction continues even with antiretroviral treatment, and even mild cognitive impairment is associated with detrimental health outcomes in older HIV+ adults. Alcohol consumption may affect the brain directly or indirectly via liver toxicity and systemic inflammation. Our past findings indicate that current heavy alcohol use is more strongly associated with cognitive/brain dysfunction among HIV+ adults than lifetime consumption, suggesting that these effects may be reversible with reductions in drinking. Towards this objective, we propose to enroll 180 HIV+ adults with heavy drinking, and then use CM with financial incentives and a wearable alcohol biosensor to maximally reduce alcohol consumption from baseline (T1) to 4-weeks later (T2). We will then conduct a motivational interview to determine perceived benefits and obstacles to drinking reduction, and conduct a final assessment 1 year later (T3), at which point persons may or may not have resumed heavy drinking. We will conduct state-of-the-art neuroimaging, cognitive, and behavioral assessments at each timepoint, and then continue to track long-term drinking and HIV outcomes in our companion Cohort (U24). The Specific Aims of this proposal are: 1) to demonstrate improved cognitive performance and brain function (fMRI) after 4-weeks of CM-induced alcohol reduction among HIV+ adults, followed by worsening of these effects 1-year later if heavy drinking resumes; 2) to demonstrate that cerebral metabolic (MRS) and neuroinflammatory (DTI-free water) markers will also improve with CM-induced alcohol reduction and worsen if drinking resumes post-CM; and 3) Determine whether perceived benefits and challenges to drinking reduction identified during motivational interviewing (MI) predict drinking reductions or relapse one-year post-CM. We will also determine whether changes in cerebral pathophysiology (MRS, DTI-FW) correspond with changes in cognition, brain function (fMRI) and serum inflammatory and liver biomarkers. In addition, we will determine which neuroimaging and baseline clinical factors are associated with long-term drinking and clinical outcomes (e.g. HIV viral suppression, liver comorbidities). In the context of this study, CM and MI are being employed as an experimental manipulation and data collection opportunity, respectively, rather than as clinical interventions per se. The A-B-A design will enable us to clearly identify whether alcohol effects on cognition and the brain are reversible, and to identify optimal strategies to promote short-term and long-term alcohol reduction in HIV+ adults. This U01 project is closely linked to the Administrative U24 (SHARC), which supports the Florida Cohort that is the source of potential participants for this study, and our Behavioral Science and Biostatistics Core (U24) that will help implement and monitor the CM, MI, and alcohol biosensor procedures.