NEUROCOGNITIVE

这是希顿公司修订后的项目申请表。神经认知项目的目的是在甲基苯丙胺(冰毒)依赖的背景下检查与艾滋病毒感染相关的神经心理学(NP)结果。我们证明，在HIV感染者中，冰毒依赖史确实增加了NP损害的风险。与这两个危险因素相关的NP损害的模式与额叶-皮质下功能障碍是一致的。在我们研究的人群中，三分之一的冰毒使用者患有慢性丙型肝炎病毒(HCV)感染。越来越多的证据表明，即使在没有晚期肝病的患者中，丙型肝炎病毒本身也可能与脑功能障碍和NP损害有关。而联合使用干扰素和利巴韦林(干扰素/RBV)可使许多感染丙型肝炎病毒的患者持续清除病毒 对人来说，它还可能引起衰弱的神经精神副作用，据报道，这种副作用在有物质使用障碍病史的人中更为常见。目前尚不清楚丙型肝炎病毒的成功清除和/或治疗相关的神经精神病学副作用是否会对长期的NP和日常功能结果产生重大影响。项目1将由两项研究组成。研究1是对三个风险组及其组合中的每一个个体的横断面评估，目的是确定冰毒、艾滋病毒和丙型肝炎病毒对神经行为的独特和联合影响，并将我们的观察结果与该计划中其他项目的观察结果联系起来，努力描述神经发病机制。研究2是一项为期18个月的纵向研究 有冰毒依赖史的HIV感染者因合并丙型肝炎病毒感染而接受干扰素/RBV治疗的调查我们将确定神经行为变化的发生率和临床意义与治疗副作用和成功实现持续病毒清除的关系，并将与Biomarkers Project合作探索此类变化的病理生理机制。在这次修订中，为了回应审查者对组之间变量差异的担忧，这可能会使解释变得困难，我们扩大了丙型肝炎病毒“唯一”风险组，以包括更多的人。 并修订了我们的统计方法，以更清楚地解决混淆中的不平衡问题。

This is a revised application for Project by Heaton. The aim of the Neurocognitive Project has been to examine neuropsychological (NP) outcomes associated with HIV infection in the context of methamphetamine (METH) dependence. We demonstrated that a history of METH dependence does confer increased risk for NP impairment in people with HIV. Patterns of NP impairments associated with both risk factors have been consistent with frontal-subcortical dysfunction. One third of METH users in our study population have chronic hepatitis C virus (HCV) infection. There is increasing evidence that HCV itself can be associated with brain dysfunction and NP impairment, even in patients without advanced liver disease. While treatment with combined interferon and ribavirin (IFN/RBV) results in sustained viral clearance in many HCV infected persons, it may also cause debilitating neuropsychiatric side effects that are reportedly more common in those with histories of substance use disorders. It is unknown whether successful HCV clearance and/or treatment-related neuropsychiatric side effects substantially affect longer term NP and everyday functioning outcomes. Project 1 will be composed of two studies. Study 1 is a cross-sectional evaluation of individuals in each of the three risk groups and their combinations, with the aim to determine the unique and combined neurobehavioral effects of METH, HIV, and HCV, and to link our observations to those of other Projects in the Program in an effort to delineate mechanisms of neuropathogenesis. Study 2 is an 18-month longitudinal investigation of HIV- individuals with history of METH dependence receiving IFN/RBV treatment for comorbid HCV infection. We will determine the incidence and clinical significance of neurobehavioral changes in relation to treatment side effects and success in achieving sustained viral clearance, and will collaborate with the Biomarkers Project in exploring pathophysiologic mechanisms of such changes. In this revision, in response to reviewer concerns regarding differences in variables among groups that could make interpretation difficult, we have expanded the HCV "only" risk group to include more persons with fewer confounds, and have revised our statistical approach to address imbalances in confounds more clearly.