Neurocognitive Effects of Opiate Agonist Treatment in HIV Infected Drug Users

描述（由申请人提供）：尽管出现了HAART， hiv相关神经认知（NC）疾病的发生率仍然很高。感染艾滋病毒的吸毒者比没有药物使用史的艾滋病毒感染者或未感染的吸毒者表现出加速和更严重的NC功能障碍。由于阿片类药物使用者中NC损伤的风险也升高，无论艾滋病毒状况如何，因此感染艾滋病毒的阿片类药物使用者存在NC损伤的附加风险。通常用于治疗阿片类药物依赖的药物如何影响NC功能障碍的进展尚不清楚。美沙酮是阿片成瘾治疗中最常用的药物，一些研究表明，美沙酮是一种全μ阿片受体激动剂，可能与NC缺陷有关。然而，这些研究在很大程度上缺乏纵向随访来评估长期美沙酮维持是否与NC功能障碍进展相关。此外，尽管美沙酮具有治疗效果，但其利用不足，2005年只有12%依赖阿片类药物的美国人接受美沙酮治疗。为了解决这个问题，丁丙诺啡在2002年被批准用于治疗阿片类药物成瘾。丁丙诺啡是一种部分阿片受体激动剂和阿片受体拮抗剂，与美沙酮相比，可能具有良好的NC作用。然而，很少有研究检查丁丙诺啡对NC的影响，而且没有研究包括纵向随访或关注艾滋病毒感染者。为了确保治疗提供者了解丁丙诺啡的全部作用，这是至关重要的

DESCRIPTION (provided by applicant): Rates of HIV-associated neurocognitive (NC) disorders remain high, despite the emergence of HAART. HIV-infected drug users exhibit accelerated and more severe NC dysfunction than either HIV-infected persons without drug use histories, or uninfected drug users. Because the risk of NC impairment is also elevated in opioid users regardless of HIV-status, there is additive risk of NC impairment for HIV-infected opioid users. How medications commonly used to treat opioid dependence affect the progression NC dysfunction is poorly understood. Methadone is the most commonly used medication for opioid addiction treatment, and some studies suggest that methadone, a full mu opioid receptor agonist, may be associated with NC deficits. However, these studies have largely lacked longitudinal follow-up to assess whether long-term methadone maintenance is associated with progression of NC dysfunction. Further, despite its therapeutic benefits, methadone is under- utilized, with only 12% of opioid-dependent Americans receiving methadone in 2005. To remedy this, buprenrophine was approved for opioid addiction treatment in 2002. Buprenorphine, a partial mu opioid receptor agonist and kappa opioid receptor antagonist, may have favorable NC effects compared to methadone. However, few studies have examined buprenorphine's NC effects, and none have included longitudinal follow-up or focused on HIV-infected persons. To ensure that treatment providers understand the full range of buprenorphine's effects, it is crucial to evaluate the relative NC effects of buprenorphine and methadone in opioid users with and without HIV infection. In this revised application, we propose to use a randomized clinical trial (RCT) design to test the hypothesis that treatment with buprenorphine is associated with significant improvement in NC function in opioid-dependent drug users with- and with- out HIV, compared to methadone. We will also examine whether HIV-infection moderates the impact of opioid agonist therapies on NC function. We will enroll and randomize 160 subjects 1:1 to 6 months of buprenorphine or methadone treatment, both of which will be delivered in the same supervised setting by experienced substance abuse treatment physicians. We will stratify randomization by HIV-serostatus, to ensure equal numbers of HIV-infected subjects in each arm. Following randomization and a one week run-in, we will measure NC function with a state-of-the art NC battery. We will then repeat the NC battery after 3 and 6 months of opioid agonist treatment. Our specific aims are: (1) to determine, in an RCT, whether buprenorphine is associated with significant improvement in NC function compared to methadone; (2) to assess the impact of buprenorphine treatment on change in NC function over time; and (3) to assess the impact of methadone treatment on changes in NC function over time. This will be the first randomized longitudinal trial investigating the impact of methadone and buprenorphine on neurocognitive outcomes. Findings from this study have the potential to impact treatment recommendations for opioid dependence for drug users with or without HIV, to improve NC outcomes, and to deepen our understanding of brain-drug interactions.