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: 10541347
• 负责人: Karsten Lunze
• 金额: $ 73.85万
• 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/10541347
• 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; Lead; Naltrexone; Outcome; Pain; Participant; Patient Self-Report; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; Placebo Control; Placebos; Population; Prevention; Prevention approach; Prevention strategy; Publishing; Randomized; Randomized Clinical Trials; Regimen; Relapse; Research; Role; Russia; Severities; Strategic Planning; Substance Use Disorder; Testing; Time; Treatment Effectiveness; United States National Institutes of Health; Viral Load result; alcohol abuse therapy; alcohol misuse; alcohol pharmacology; antiretroviral therapy; arm; brief intervention; effective therapy; efficacy evaluation; efficacy testing; experience; gabapentin; improved; medication compliance; multidisciplinary; opioid use disorder; prevent; primary outcome; reduced alcohol use; 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.

项目摘要 /摘要 结束HIV流行需要为关键人群实现HIV病毒载量（HVL）。不良 艾滋病毒（PWH）患者的饮酒是在艾滋病毒多个阶段达到HVL抑制的障碍 护理级联。饮酒在PWH中很常见，导致较低的抗逆转录病毒疗法（ART）依从性 和HVL抑制，减轻治疗作为预防的有效性（TASP），这是一个关键策略 防止艾滋病毒传播。因此，治疗饮酒是一种支持PWH不健康的机制 沿艾滋病毒护理级联的饮酒。实际上，先前的研究表明，减少酒精的干预措施 使用积极影响艾滋病毒的结果。加巴喷丁有效地减少饮酒，可能是 对疼痛状况的有效治疗方法，例如与HIV相关的感觉神经病。然而， 尚未确定加巴喷丁在实现该人群中实现HVL抑制的作用。我们的假设是 有效的药物治疗（即加巴喷丁）将有助于PWH参与艾滋病毒护理，遵守 艺术，并实现HVL抑制。我们提出加巴喷丁以减少酒精并改善病毒载荷 抑制（圣杯）随机，双盲，安慰剂对照临床试验，以评估 Gabapentin vs.安慰剂以实现PWH之间的HVL抑制。研究人群将是沉重的饮酒者 在过去的一年中，霍夫（HIV）有可检测的病毒载荷，佐普特（Dospite）被开了大艺术。参与者 （n = 300）将被随机分为1：1，以接收gabapentin（1800mg/天目标剂量）或安慰剂3 月份；两臂都将采用一次性简短的干预来减少酒精的使用。 Grail的目的是1）测试 加巴喷丁与安慰剂的功效在3个月（主要结果）和6＆时实现无法检测到的HVL的功效 12个月（次要结果）； 2）与安慰剂相比，评估加巴喷丁的影响：a） 饮酒，b）疼痛严重程度，c）自我报告的艺术依从性和d）参与艾滋病毒护理 为了探索加巴喷丁可能导致HVL抑制的潜在机制。这项研究将进行 位于俄罗斯的综合性饮酒，吸毒和艾滋病毒的背景下。我们的多学科团队 在俄罗斯成功进行随机临床试验的广泛记录，包括 PWH中的药理学试验（例如Gabapentin）。俄罗斯，艾滋病毒和大量饮酒的环境 比美国更普遍，将有效地研究PWH中的酒精使用。 获得的知识将适用于在美国和全球享有艾滋病毒的人群。提议的审判 加巴喷丁很重要 使用并实现HVL抑制。如果证明是有效的，则这种高度概括的务实方法 TASP可以在各种临床环境中实施，从而使其成为艾滋病毒的实际补充 预防工具包。