Reducing Heavy Drinking to Optimize HIV/AIDS Treatment and Prevention

项目总结/摘要 很少有治疗方法被评估以减少大量饮酒、酒精滥用和依赖的影响 艾滋病感染者的研究。这些酒精消费水平与减少遵守有关， 高效抗逆转录病毒疗法（HAART），增加病毒突变的可能性，增强疾病 进展，促进肝损伤，增加性风险。纳洛酮，当与 咨询，是一种有效的治疗酗酒，酒精滥用和依赖，但没有数据 在HIV感染患者中的使用或疗效。这项拟议的研究比较了纳洛酮和安慰剂在24- 在HAART非依从性HIV感染患者中进行的一项为期一周的随机双盲安慰剂对照临床试验 在HIV诊所中重度饮酒、酒精滥用或依赖（N=154）。为了确定长期 所有患者将在9个月和12个月时接受随访。随机分配至纳洛酮组的患者 最初将接受口服每日制剂，如果耐受，将转移到每月延长 释放制剂。所有患者都将接受药物管理（MM）的咨询平台 联合用药指导（MC）（MM/MC）。MM/MC是一种复合手动治疗， 这是一种适合在艾滋病毒初级保健环境中实施的近似治疗类型。它 重点是通过一系列简短的措施来减少大量饮酒（MM）和提高药物依从性（MC）。 由受过医学培训的提供者提供的干预措施。数据分析的目的是 随机分配接受纳洛酮+ MM/MC与安慰剂+ MM/MC的患者治疗样本。的 主要研究结果是坚持HAART药物治疗。次要研究结果包括以下频率： 酗酒、HIV病毒突变（使用标准检测和超深度测序）、CD 4变化 淋巴细胞计数和HIV RNA、酒精-HAART肝毒性和性风险行为。小说 该建议的方面包括：1）综合现场酒精和艾滋病毒治疗; 2）使用扩展的 释放纳洛酮，这可能会提高这一患者人群的依从性， 依从性具有挑战性; 3）使用几种HAART依从性措施，包括药房补充 数据; 4）使用复杂的技术来检查新病毒突变的发展，包括 新的微小变异的检测;和5）收集关于治疗对肝脏影响的详细数据。的 由一个经验丰富的艾滋病毒和成瘾研究人员团队进行的拟议研究将有助于确定 纳洛酮和循证咨询在HAART非依从性受试者酒精问题。

PROJECT SUMMARY/ABSTRACT Few treatments have been evaluated to reduce the impact of heavy drinking, alcohol abuse and dependence on HIV-infected patients. These levels of alcohol consumption are associated with decreased adherence to highly active antiretroviral therapy (HAART), an increased likelihood of viral mutations, enhanced disease progression, promotion of liver injury, and increased sexual risk taking. Naltrexone, when combined with counseling, is an effective treatment for heavy drinking, alcohol abuse and dependence yet there are no data on its use or efficacy in HIV-infected patients. The proposed study compares naltrexone to placebo in a 24- week randomized double-blind placebo-controlled clinical trial in HAART-non-adherent HIV-infected patients with heavy drinking, alcohol abuse or dependence (N=154 ) in an HIV clinic. To determine the long-term impact of treatment, all patients will undergo follow-up at 9 and 12 months. Patients randomized to naltrexone will initially receive the oral daily formulation and, if tolerated, will be transferred to the monthly extended release formulation. All patients will receive the counseling platform of Medication Management (MM) combined with Medication Coaching (MC) (MM/MC). MM/MC is a compound manualized treatment intended to approximate the type of treatment that would be suitable for implementation in an HIV primary care setting. It focuses on reducing heavy drinking (MM) and improving medication adherence (MC) through a series of brief interventions delivered by a medically trained provider. Data analyses will be conducted on the intention to treat sample of patients randomly assigned to receive naltrexone + MM/MC versus placebo + MM/MC. The primary study outcome is adherence to HAART medications. Secondary study outcomes include frequency of heavy drinking, HIV viral mutations (using standard assays and ultra-deep sequencing), change in CD4 lymphocyte counts and HIV RNA, alcohol-HAART hepatotoxicity, and sexual risk behaviors. The novel aspects of this proposal include: 1) Integrated on-site alcohol and HIV treatment; 2) The use of extended release naltrexone which is likely to improve adherence in this patient population for whom medication adherence is challenging; 3) The use of several measures for HAART adherence including pharmacy refill data; 4) The use of sophisticated techniques for examining the development of new viral mutations including the detection of new minor variants; and 5) Collection of detailed data on the hepatic effects of treatment. The proposed study, conducted by an experienced team of HIV and addiction researchers, will help define the role of naltrexone and evidence-based counseling in HAART-non-adherent subjects with alcohol problems.