Neurobehavioral Deficits in HIV/HCV Infection Pre/Post Anti-HCV Therapy

此应用程序响应于：PA-07-089中枢神经系统和 部分响应：PA-07-338 HIV治疗依从性研究。合并感染 人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）是一种新兴的医疗保健 在美国，大约三分之一的艾滋病毒感染者是合并感染者。 HCV。HIV和HCV感染可引起一系列认知、精神和中枢神经系统疾病， 神经系统异常越来越多的人有理由相信，即使在 没有艾滋病毒或其他cormorbid条件，本身是神经致病性。的主要治疗方法 HCV是聚乙二醇干扰素α和利巴韦林（PEG-IFN/RBV）。治疗的成功与 患者是否能够耐受处方剂量和治疗持续时间。研究还没有 重点关注患者是否可能漏服或跳过剂量，这与健康状况类似。 研究HIV单一感染。考虑到HCV持续缓解率相对较低， （大约40-50%），并考虑到服用有效的药物组合的困难， 持续一段时间（大多数将接受48周的治疗），可以合理假设， 次优的依从性可能对治疗失败负有一定责任。 这项为期五年的纵向研究旨在确定：（1）PEG治疗的影响- IFN/RBV对神经认知、神经精神和神经影像学参数的影响以及 共病HIV感染改变了这种反应;（2）是否参与者谁实现了SVR 与对照组相比， 基线表现和（3）参与者对抗HCV药物的依从性程度 方案影响神经功能以及获得持续病毒学的可能性 反应我们特别感兴趣的是确定如何（或是否）共病艾滋病毒感染改变 治疗相关神经变化的表达。我们将招募330名参与者，其中165人是 HIV/HCV合并感染者和165名HCV单一感染者，以获得最终样本， 200名参与者完成治疗。研究参与者将接受一系列评估， 开始治疗前，治疗后12周， 开始治疗，然后在治疗完成后12周。嵌套队列 将接受质子磁共振波谱（MRS）和扩散张量成像（DTI）， 每个研究时间点。我们将采用增长建模和多组路径分析作为 主要分析技术。项目叙述：人类免疫缺陷病毒（HIV）和丙型肝炎合并感染 越来越多的人认识到丙型肝炎病毒（HCV）是一个紧迫的公共卫生问题， 在美国，HCV引起的死亡将很快超过HIV引起的死亡。虽然有 虽然治疗HCV的药物通常有效，但这些药物也是有毒的， 影响大脑功能并导致药物依从性问题。这项研究将确定如何 同时感染HIV和HCV会影响大脑，HCV治疗如何影响大脑功能， 以及对HCV药物的依从性如何影响对治疗的反应和神经功能。 特别令人感兴趣的是艾滋病毒合并感染如何影响对治疗的反应。

This application is responsive to: PA-07-089 HIV Infection of the Central Nervous System and partially responsive to: PA-07-338 HIV Treatment Adherence Research. Co-infection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is a burgeoning healthcare concern, as approximately one third of all HIV-infected patients in the United States are co-infected with HCV. Infection with HIV and HCV can give rise to a host of cognitive, psychiatric and central nervous system abnormalities. Increasingly, there is reason to believe that HCV, even in the absence of HIV or other cormorbid conditions, is itself neuropathogenic. The main treatment for HCV is pegylated interferon alfa and ribavirin (PEG-IFN/RBV). Treatment success is linked to whether patients can tolerate prescribed dosages and duration of therapy. Research has yet to focus on whether patients may miss or skip doses, an analogous situation to what has been well studied in HIV mono-infection. Given the relatively low rates of sustaining HCV remission (approximately 40-50%) and given the difficulty of taking a potent combination of medications for a sustained period of time (most will be on treatment for 48 weeks), it is reasonable to assume that suboptimal adherence might share some responsibility for treatment failure. This five year longitudinal study seeks to determine: (1) The impact of treatment with PEG- IFN/RBV on neurocognitive, neuropsychiatric, and neuroimaging parameters and the degree to which comorbid HIV infection alters this response; (2) whether participants who achieve a SVR demonstrate statistically and clinically significant improvements in neuro-function compared to baseline performance and (3) the degree to which adherence to participants' anti-HCV medication regimen impacts neural function as well as the likelihood of obtaining a sustained virologic response. We are particularly interested in determining how (or if) co-morbid HIV infection alters the expression of treatment related neuro-changes. We will enroll 330 participants, 165 who are HIV/HCV co-infected and 165 who are HCV mono-infected in order to obtain an ultimate sample of 200 participants who complete therapy. Study participants will be evaluated with a series of neuropsychological and psychiatric measures prior to beginning treatment, 12 weeks after treatment has been initiated, and then 12 weeks following treatment completion. A nested cohort will undergo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) at each study timepoint. We will employ growth modeling and multiple group path analysis as the primary analytic techniques. Project Narrative: Co-infection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is increasingly recognized as a pressing public health concern as the number of deaths due to HCV will soon outpace deaths due to HIV in the United States. While there are medications for HCV that are frequently effective, these drugs are also toxic and may adversely affect brain function and cause problems with medication adherence. This study will determine how co-infection with both HIV and HCV affects the brain, how treatment for HCV affects brain function, and how adherence to HCV medications affects response to treatment and neurological functions. Of particular interest is how HIV co-infection affects response to treatment.