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.

项目概要/摘要 结束艾滋病毒流行需要对不健康人群实现艾滋病毒病毒载量（HVL）抑制。 HIV 感染者 (PWH) 的饮酒是在 HIV 多个阶段实现 HVL 抑制的障碍 酗酒在感染者中很常见，导致抗逆转录病毒治疗 (ART) 依从性较低。 和 HVL 抑制，降低了治疗即预防 (TasP) 的有效性，这是治疗作为预防的关键策略 因此，预防艾滋病毒传播是支持艾滋病毒感染者不健康的一种机制。 事实上，先前的研究表明，可以采取干预措施来减少饮酒。 使用加巴喷丁可有效减少饮酒量，并可能对艾滋病毒结果产生积极影响。 一种有效治疗疼痛病症的方法，例如与艾滋病毒相关的感觉神经病。 加巴喷丁在该人群中实现 HVL 抑制的作用尚未确定。 有效的药物酒精治疗（即加巴喷丁）将帮助感染者参与艾滋病毒护理，坚持 我们建议使用加巴喷丁来减少酒精含量并改善病毒载量。 抑制 (GRAIL) 随机、双盲、安慰剂对照临床试验，旨在评估 加巴喷丁与安慰剂对比，以实现感染者 HVL 抑制 研究人群为酗酒者。 尽管已接受抗逆转录病毒治疗，但在过去一年仍可检测到病毒载量的艾滋病毒参与者。 (N=300) 将按 1:1 随机分配接受加巴喷丁（1800 毫克/天目标剂量）或安慰剂 3 次 几个月；双臂将采用一次性短暂干预来减少饮酒，目的是 1) 测试。 加巴喷丁与安慰剂相比，在 3 个月（主要结果）和 6 个月时达到不可检测的 HVL 的效果 12 个月（次要结果）；以及 2) 评估加巴喷丁与安慰剂相比对以下方面的影响： 饮酒量，b) 疼痛严重程度，c) 自我报告的 ART 依从性，以及 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，本研究将进行。 在俄罗斯，在不健康饮酒、吸毒和艾滋病毒流行的背景下，我们的多学科团队。 拥有在俄罗斯成功进行随机临床试验的广泛记录，包括 在俄罗斯艾滋病毒和酗酒的环境中进行的药理学试验（例如加巴喷丁）。 比美国更为普遍，这将有助于有效地研究干预艾滋病毒感染者饮酒的情况。 所获得的知识将适用于美国和全球的艾滋病毒感染者。 加巴喷丁具有重要意义，因为它采用 TasP 方法通过针对酒精来预防 HIV 传播 如果被证明是有效的，那么这种高度通用的实用方法可以实现 HVL 抑制。 TasP 可以在各种临床环境中实施，从而使其成为 HIV 治疗的实用补充 预防工具包。