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

项目摘要/摘要 结束艾滋病毒流行需要在关键人群中实现艾滋病毒病毒载量(HVL)抑制。不健康 艾滋病毒携带者使用酒精是在艾滋病毒多个阶段达到人类免疫缺陷病毒抑制的障碍 关爱层出不穷。酒精使用在PWH中很常见，并导致抗逆转录病毒治疗(ART)依从性较低 和HVL抑制，减轻治疗作为预防(TasP)的有效性，这是 防止艾滋病毒传播。因此，治疗酒精使用是支持不健康的PWH的一种机制 酒精的使用伴随着艾滋病护理的级联反应。事实上，先前的研究表明，减少酒精含量的干预措施 使用会对艾滋病毒的结果产生积极影响。加巴喷丁对减少酒精消耗量有效，可能是 一种有效的治疗疼痛状况的方法，例如艾滋病毒相关的感觉神经病。然而， 加巴喷丁在这一人群中实现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)将有助于威斯康星医院从事艾滋病毒护理，坚持 ART，并实现了对HVL的抑制。我们建议加巴喷丁用于减少酒精和提高病毒载量 抑制率(GRAIL)随机、双盲、安慰剂对照临床试验 加巴喷丁与安慰剂在PWH中实现HVL抑制的比较。研究人群将是酗酒者 尽管开了抗逆转录病毒药物的处方，但在过去的一年里，艾滋病毒携带者的病毒载量可被检测到。参与者 (n=300)将以1：1的随机比例接受加巴喷丁(1800毫克/天的目标剂量)或安慰剂治疗3次 两个月；两个部门都将采取一次性的短暂干预措施，以减少酒精使用。圣杯的目标是测试 加巴喷丁与安慰剂相比，在3个月(主要结果)和6个月和6个月时实现未检测到的HVL的疗效 12个月(次要结果)；以及2)评估加巴喷丁与安慰剂在以下方面的影响：a) 酒精消费，b)疼痛严重程度，c)自我报告的抗逆转录病毒疗法坚持，以及d)参与艾滋病毒护理，#年 目的探讨加巴喷丁抑制门静脉高压血症的可能机制。这项研究将需要 在俄罗斯，在不健康的酗酒、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方面有广泛的记录，包括 威斯康星医院的药理试验(如加巴喷丁)。俄罗斯，一个艾滋病毒和大量饮酒的环境 比美国更普遍，这将使对威斯康星医院酒精使用干预的有效研究成为可能。这个 所获得的知识将适用于美国和全球艾滋病毒携带者。拟议的审判 加巴喷丁意义重大，因为它采用了一种TasP方法，通过靶向酒精来防止艾滋病毒传播 使用和实现高压线抑制。如果被证明是有效的，这种高度概括的务实方法将有助于 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。

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.