Addressing Alcohol/HIV Consequences in Substance Dependence - Boston ARCH Cohort

描述(由申请人提供)：不健康的饮酒在艾滋病毒感染者中很常见，并对健康造成不利影响。注射吸毒占艾滋病毒感染病例的五分之一，因此阿片类药物依赖也很常见。超过三分之一的艾滋病毒感染者和其他吸毒者饮酒过量。研究的重点是艾滋病毒感染者的酒精或药物使用，但对酒精对受多种滥用物质影响的艾滋病毒感染者的健康影响知之甚少。这项提议是乌干达、俄罗斯、波士顿酒精研究网络艾滋病毒/艾滋病问题合作(城市ARCH)联盟的一部分，该联盟的目标是研究酒精对艾滋病毒疾病的影响并减轻其危害。这项建议的目的是准确描述受多种物质影响的艾滋病毒感染者的酒精使用和后果，并实施观察性和干预性研究，以了解和减少酒精的危害。该提案有3个具体目标：1)扩大和继续现有的队列，以建立由250名受多种物质影响的艾滋病毒感染者的波士顿拱形纵向队列--酒精使用的范围，以及所有有物质依赖或注射吸毒的人。2)同时用一种药物治疗酗酒和阿片依赖。酒精风险阿片类药物治疗(Twofer)试验将在3个月时评估大剂量丁丙诺啡(32 Mg)与标准剂量(16 Mg)相比是否减少了大量饮酒，这是一项随机、双盲、安慰剂对照试验，对象是100名有阿片类药物依赖和大量饮酒的HIV感染成年队列参与者。如果有效，丁丙诺啡，一种治疗阿片依赖的方法，可以很容易地传播为艾滋病毒感染者和阿片依赖者使用不健康酒精的治疗方法，因为只需要调整剂量。3)由于酒精、阿片类药物的使用、艾滋病毒感染和抗逆转录病毒治疗可能影响骨骼健康并增加骨折风险，对队列数据的分析将确定饮酒对所有队列参与者在12-42个月内骨密度和微结构变化的独立影响(通过高分辨率计算机断层扫描)。该队列将产生酒精对骨骼影响的数据，这是确定艾滋病毒感染者危险饮酒量和建议他们与酒精相关的风险的重要信息。因此，这些研究将为减轻受多种物质影响的艾滋病毒感染成年人的酒精后果提供实质性的新知识。 公共卫生相关性：艾滋病毒疾病是可以有效治疗的，但过量饮酒会干扰治疗，并导致骨质流失，特别是在滥用其他药物的人中。这项研究将对艾滋病毒感染者进行研究，以发现哪些量的酒精会增加骨折的风险，并看看一种用于药物成瘾的药物是否也可以减少大量饮酒。研究结果将有助于建议艾滋病毒感染者限制饮酒以防止骨折，并可能找到一种减少饮酒和改善健康的新疗法。

DESCRIPTION (provided by applicant): Unhealthy alcohol use is common among HIV-infected persons and it adversely affects health. Injection drug use accounts for 1 in 5 cases of HIV infection, thus opioid dependence is also common. More than one-third of those with HIV infection and other drug use drink too much alcohol. Research has focused on either alcohol or drug use in HIV-infected individuals, but much less is known about alcohol's health effects in HIV- infected people affected by multiple substances of abuse. This proposal is a component of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium, whose goal is to examine the consequences of alcohol on HIV disease and to mitigate its harms. The objective of this proposal is to accurately characterize alcohol use and consequences in people with HIV infection affected by multiple substances, and to implement observational and intervention studies to understand and reduce alcohol's harm. The proposal has 3 specific aims: 1) To expand and continue an existing cohort to establish the longitudinal Boston ARCH Cohort of 250 HIV-infected men and women affected by multiple substances-a spectrum of alcohol use, and all with substance dependence or Injection drug use. 2) To treat both heavy drinking and opioid dependence with one medication. The Treating With Opioids For Ethanol Risks (TWOFER) trial will assess if high-dose buprenorphine (32mg) reduces heavy drinking compared to standard-dose (16mg) at 3 months in a randomized double-blind placebo-controlled trial among 100 HIV-infected adult Cohort participants with opioid dependence and heavy drinking. If efficacious, buprenorphine, a treatment for opioid dependence, could be easily disseminated as a treatment for unhealthy alcohol use in people with HIV infection and opioid dependence as only dose adjustment is required. 3) Because alcohol, opioid use, HIV infection and antiretroviral therapy may affect bone health and increase fracture risk, analysis of cohort data will determine the independent effect of alcohol consumption on changes in bone mineral density and microarchitecture (by high-resolution computed tomography) prospectively in all Cohort participants over 12-42 months. The Cohort will yield data on alcohol effects on bone, important information for defining risky drinking amounts in people with HIV infection and for advising them on alcohol-related risks. Thus, these studies will provide substantial new knowledge for mitigating alcohol consequences among HIV-infected adults affected by multiple substances. PUBLIC HEALTH RELEVANCE: HIV disease can be treated effectively, but drinking too much interferes with treatment and causes bone loss, especially among those who abuse other drugs. This research will study people with HIV infection to discover what amounts of alcohol increase risk of fractures, and to see whether a medication used for drug addiction can also reduce heavy drinking. Findings will be useful for advising people with HIV infection about drinking limits to prevent fractures and may identify a new treatment to reduce drinking and improve health.