Neurocognitive Effects of Buprenorphine Among HIV+ Opioid Users

丁丙诺啡对 HIV 阿片类药物使用者的神经认知影响

• 批准号: 7617365
• 负责人: JULIA H. ARNSTEN
• 金额: $ 18.56万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617365
• 关键词: AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Agonist; American; Attenuated; Biological Markers; Blood Platelets; Blood specimen; Buprenorphine; Cells; Child; Cognitive; Decision Making; Deglutition; Drug Addiction; Drug abuse; Drug user; Epidemic; HIV; HIV Infections; Heroin; Improve Access; Injectable; Injecting drug user; Maintenance; Measures; Methadone; Nervous System Physiology; Neurocognitive; Opiate Addiction; Opioid; Outcome; Performance; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Plasma; Play; Process; Proteomics; Receptor Activation; Recruitment Activity; Smoke; Testing; United States Food and Drug Administration; cohort; design; follow-up; improved; kappa opioid receptors; methadone maintenance; mu opioid receptors; neurocognitive test; opioid abuse

Opioid abuse has undergone a resurgence in the last decade. Although many opioids can be swallowed, snorted, or smoked, injectable opioids (especially heroin) have figured most prominently in the HIV epidemic. Injection drug users and their partners and children currently account for 36% of cumulative AIDS cases in the U.S. To improve access to pharmacotherapy for opioid dependence, the federal Drug Addiction Treatment Act (2000) and the Food and Drug Administration (2002) approved buprenrophine for opioid addiction treatment. Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at the kappa opioid receptor. Because mu receptor activation has been shown to stimulate HIV expression in monocytic cells, while kappa receptor activation inhibits HIV expression in these cells, buprenorphine's activity at the kappa receptor may be attenuate HIV expression. This may in turn be important for disrupting the synergistic processes that HIV infection and opioid dependence play in advancing neurocognitive decline. In this proposal, we will test the overarching hypothesis that pharmacological antagonism of kappa opioid receptors, such as that obtained with buprenorphine, may improve neurocognitive function in opioiddependent drug users with HIV infection. We will examine the impact of buprenorphine on changes in neurocognitive (NC) function among opioid-dependent persons with and without HIV-infection, and create a plasma bank to identify biomarkers of neurocognitive changes associated with buprenorphine initiation and maintenance. A cohort of 40 HIV-infected opioid-dependent persons and 40 HIV-seronegative opioiddependent perons newly initiated on buprenorphine will be recruited and serial NC testing will be adminstered and serial blood samples obtained. We will conduct a proteomic analysis to identify biomarkers in platelet poor plasma of buprenorphine administration and neurocognitive outcome in fifteen HIV-infected opioid-dependent persons, using a pre/post design.

阿片类药物滥用在过去十年中死灰复燃。尽管许多阿片类药物可以被吞下， 吸食或吸食注射类阿片类药物(特别是海洛因)在艾滋病毒流行中占主导地位。 注射吸毒者及其伴侣和儿童目前占#年累计艾滋病病例的36%。 美国为了改善阿片类药物依赖的药物治疗，联邦药物成瘾 《治疗法》(2000)和食品和药物管理局(2002)批准丁丙诺芬用于阿片类药物 上瘾治疗。丁丙诺啡是Mu阿片受体的部分激动剂和阿片受体的拮抗剂。 Kappa阿片受体。因为Mu受体的激活已经被证明能刺激HIV在 单核细胞，而kappa受体激活抑制这些细胞中HIV的表达，丁丙诺啡 Kappa受体的活性可能是减弱HIV的表达。这反过来可能对扰乱 HIV感染和阿片类药物依赖在促进神经认知中的协同作用 拒绝。在这项提案中，我们将检验kappa的药理拮抗作用这一重要假设。 阿片受体，如丁丙诺啡获得的受体，可能改善阿片依赖患者的神经认知功能 感染艾滋病毒的吸毒者。我们将研究丁丙诺啡对 感染和不感染艾滋病毒的阿片依赖者的神经认知(NC)功能，并创造 血浆库用于识别与丁丙诺啡启动和治疗相关的神经认知改变的生物标记物 维修。40名感染艾滋病毒的阿片依赖者和40名HIV血清阴性的阿片依赖者组成的队列 将招募新开始服用丁丙诺啡的贝隆，并将进行系列NC测试 获得经管理的和连续的血液样本。我们将进行蛋白质组学分析以确定生物标记物 丁丙诺啡治疗15例HIV感染者的血小板贫乏与神经认知结局 阿片依赖者，采用前/后设计。