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.

在过去的十年中，阿片类药物滥用发生了复兴。尽管许多阿片类药物都可以吞咽，但 在艾滋病毒的流行中，nort弱或熏制的注射阿片类药物（尤其是海洛因）最为突出。 注射吸毒者及其伴侣和儿童目前占累积艾滋病案件的36％ 美国为改善阿片类药物依赖的药物疗法的机会，联邦药物成瘾 治疗法（2000年）和食品药品监督管理局（2002）批准阿片类药物的丁丙诺章 成瘾治疗。丁丙诺啡是MU阿片受体的部分激动剂，也是拮抗剂 Kappa阿片类药物受体。因为已显示MU受体激活刺激HIV表达 单核细胞，而Kappa受体激活抑制了这些细胞中的HIV表达，丁丙诺啡的表达 KAPPA受体的活性可能会减弱HIV表达。反过来，这可能对破坏很重要 艾滋病毒感染和阿片类药物依赖性在推动神经认知方面发挥的协同过程 衰退。在此提案中，我们将检验以下总体假设，即Kappa的药理学对抗 阿片类药物受体，例如用丁丙诺啡获得的受体，可以改善阿片类依赖性的神经认知功能 艾滋病毒感染的吸毒者。我们将研究丁丙诺啡对变化的影响 有和没有HIV感染的阿片类药物依赖性人的神经认知（NC）功能，并创建一个 等离子体库确定与丁丙诺啡启动相关的神经认知变化的生物标志物 维护。由40名HIV感染的阿片类药物依赖性人和40个HIV副反词的阿片类药物依赖性的队列 将招募在丁丙诺啡上新发起的Perons，串行NC测试将是 获得了守护和连续的血液样本。我们将进行蛋白质组学分析以识别生物标志物 在血小板中，丁丙诺啡给药和神经认知结果的血浆较差 使用前/邮政设计，取决于阿片类药物。