Gabapentin to Reduce Alcohol and Improve Viral Load Suppression - Promoting "Treatment as Prevention"

加巴喷丁减少饮酒并改善病毒载量抑制——促进“治疗即预防”

• 批准号: 10706554
• 负责人: Karsten Lunze
• 金额: $ 64.81万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706554
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Address; Adherence; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic beverage heavy drinker; Alcohols; Caring; Clinical; Clinical Trials; Controlled Clinical Trials; Country; Dose; Double-Blind Method; Drug usage; Epidemic; Europe; Goals; HIV; Heavy Drinking; Intervention; Knowledge; Naltrexone; Outcome; Pain; Participant; Patient Self-Report; Persons; Pharmaceutical Preparations; Pharmacology Study; Placebo Control; Placebos; Population; Prevention; Prevention approach; Prevention strategy; Publishing; Randomized; Regimen; Research; Role; Russia; Severities; Strategic Planning; Substance Use Disorder; Testing; Treatment Effectiveness; United States National Institutes of Health; Viral Load result; alcohol abuse therapy; alcohol misuse; antiretroviral therapy; arm; brief intervention; effective therapy; efficacy evaluation; efficacy testing; experience; gabapentin; improved; medication compliance; multidisciplinary; opioid use disorder; pharmacologic; prevent; primary outcome; randomized, clinical trials; reduced alcohol use; relapse prevention; secondary outcome; sensory neuropathy; study population; substance use; syndemic; therapy adherence; transmission process; treatment as prevention

PROJECT SUMMARY / ABSTRACT Ending the HIV epidemic requires achieving HIV viral load (HVL) suppression for key populations. Unhealthy alcohol use by people with HIV (PWH) is a barrier to reaching HVL suppression at multiple stages of the HIV care cascade. Alcohol use is common among PWH and results in lower antiretroviral therapy (ART) adherence and HVL suppression, mitigating the effectiveness of Treatment as Prevention (TasP), a key strategy for preventing HIV transmission. Treating alcohol use is therefore a mechanism to support PWH with unhealthy alcohol use along the HIV care cascade. In fact, prior studies demonstrate that interventions to reduce alcohol use positively impact HIV outcomes. Gabapentin is efficacious for decreasing alcohol consumption and may be an effective treatment for painful conditions, such as HIV-associated sensory neuropathies. However, gabapentin’s role in achieving HVL suppression in this population has not been established. Our hypothesis is that effective pharmacological alcohol treatment (i.e., gabapentin) will help PWH engage in HIV care, adhere to ART, and achieve HVL suppression. We propose the Gabapentin to Reduce Alcohol and Improve Viral Load Suppression (GRAIL) randomized, double-blinded, placebo-controlled clinical trial to evaluate the efficacy of gabapentin vs. placebo to achieve HVL suppression among PWH. The study population will be heavy drinkers with HIV who had a detectable viral load in the past year, despite having been prescribed ART. Participants (N=300) will be randomized 1:1 to receive either gabapentin (1800mg/day target dose) or placebo for 3 months; both arms will employ a one-time brief intervention to reduce alcohol use. GRAIL aims to 1) test the efficacy of gabapentin versus placebo to achieve undetectable HVL at 3 months (primary outcome) and at 6 & 12 months (secondary outcomes); and 2) to assess the impact of gabapentin compared to placebo on: a) alcohol consumption, b) pain severity, c) self-reported ART adherence, and d) engagement in HIV care, in order to explore potential mechanisms by which gabapentin may lead to HVL suppression. This study will take place in Russia, in a context of syndemic unhealthy alcohol use, drug use, and HIV. Our multi-disciplinary team has an extensive track record of successfully conducting randomized clinical trials in Russia, including pharmacological trials (e.g., gabapentin) in PWH. Russia, a setting in which HIV and heavy alcohol use are more prevalent than in the US, will enable efficient study of intervening on alcohol use among PWH. The knowledge gained will be applicable to populations living with HIV in the US and globally. The proposed trial of gabapentin is significant as it employs a TasP approach to prevent transmission of HIV by targeting alcohol use and achieving HVL suppression. If shown to be effective, this highly generalizable pragmatic approach to TasP can be implemented in a variety of clinical settings, thus making it a practical addition to the HIV prevention toolkit.

项目总结/摘要 结束艾滋病毒流行需要实现对关键人群的艾滋病毒载量（HVL）抑制。不健康 HIV感染者（PWH）饮酒是在HIV多个阶段达到HVL抑制的障碍 护理级联。酗酒在PWH中很常见，导致抗逆转录病毒治疗（ART）依从性降低 和HVL抑制，降低治疗即预防（TasP）的有效性，这是治疗的关键策略， 预防艾滋病毒传播。因此，治疗酒精使用是一种机制，以支持威尔斯亲王医院的不健康 酒精的使用沿着艾滋病的治疗。事实上，先前的研究表明， 使用积极影响艾滋病毒结果。加巴喷丁对于减少酒精消耗是有效的， 一种有效的治疗疼痛的条件，如艾滋病毒相关的感觉神经病变。但是，在这方面， 加巴喷丁在该人群中实现HVL抑制的作用尚未确定。我们的假设是 有效的药物酒精治疗（即，加巴喷丁）将有助威尔斯亲王医院参与爱滋病护理工作， ART，并实现HVL抑制。我们建议加巴喷丁减少酒精和改善病毒载量 抑制（GRAIL）随机、双盲、安慰剂对照临床试验，以评价 加巴喷丁与安慰剂在PWH中实现HVL抑制。研究人群将是重度饮酒者 在过去的一年中，尽管接受了ART治疗，但病毒载量可检测到的HIV感染者。 （N=300）将以1：1的比例随机接受加巴喷丁（1800 mg/天目标剂量）或安慰剂治疗3天 两组都将采用一次性短暂干预来减少酒精使用。GRAIL旨在1）测试 加巴喷丁与安慰剂相比在3个月（主要结局）和6个月（主要结局）时达到不可检测HVL的疗效 12个月（次要结局）;和2）评估加巴喷丁与安慰剂相比对以下方面的影响：a） 饮酒，B）疼痛严重程度，c）自我报告的ART依从性，以及d）参与HIV护理， 探讨加巴喷丁抑制HVL的可能机制。这项研究将采取 在俄罗斯，在不健康的酒精使用，药物使用和艾滋病毒的背景下。我们的多学科团队 拥有在俄罗斯成功开展随机临床试验的广泛记录，包括 药理学试验（例如，加巴喷丁）。在俄罗斯，艾滋病毒和酗酒是 比美国更普遍，将使有效的研究干预PWH中的酒精使用。的 所获得的知识将适用于美国和全球的艾滋病毒感染者。拟议的审判 加巴喷丁是重要的，因为它采用了TasP方法，以防止艾滋病毒的传播，针对酒精 使用并实现HVL抑制。如果被证明是有效的，这种高度普遍化的务实方法， TasP可以在各种临床环境中实施，从而使其成为HIV的实用补充。 预防工具包。