Neurocognitive Effects of Buprenorphine Among HIV+ Opioid Users

类阿片滥用在过去十年中有所抬头。虽然许多阿片类药物可以吞咽， 鼻吸或吸食的可注射阿片类药物（尤其是海洛因）在艾滋病毒流行中占最突出的地位。 注射毒品使用者及其伴侣和儿童目前占艾滋病累积病例的36%， 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年）和食品和药物管理局（2002年）批准丁丙诺啡用于阿片类药物 戒毒治疗丁丙诺啡是μ阿片受体的部分激动剂和μ阿片受体的拮抗剂。 κ阿片受体因为μ受体激活已被证明刺激HIV表达， 单核细胞，而κ受体激活抑制HIV在这些细胞中的表达，丁丙诺啡的 对κ受体的活性可以减弱HIV表达。这反过来可能对破坏 艾滋病毒感染和阿片类药物依赖在促进神经认知方面发挥的协同作用 下降在这个提议中，我们将测试总体假设，即kappa的药理学拮抗作用 阿片受体，如丁丙诺啡，可改善阿片依赖性神经认知功能， 感染艾滋病毒的吸毒者。我们将研究丁丙诺啡对 神经认知（NC）功能的阿片类药物依赖者与艾滋病毒感染，并创建一个 血浆库，以确定与丁丙诺啡开始相关的神经认知变化的生物标志物， 上维护40例HIV感染阿片类药物依赖者和40例HIV血清阴性阿片类药物依赖者的队列研究 将招募新开始丁丙诺啡治疗的受试者，并进行系列NC检测。 给药并采集系列血样。我们将进行蛋白质组学分析， 丁丙诺啡对15例HIV感染者血小板减少血浆中神经认知功能影响 阿片类药物依赖者，使用前/后设计。

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.