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

描述(申请人提供)：本申请是对PA-07-089 HIV感染中枢神经系统和部分响应：PA-07-338 HIV治疗依从性研究。人类免疫缺陷病毒(HIV)和丙型肝炎病毒(丙型肝炎病毒)的混合感染是一个新兴的医疗保健问题，因为美国大约三分之一的艾滋病毒感染患者是丙型肝炎病毒混合感染。感染艾滋病毒和丙型肝炎病毒可导致一系列认知、精神和中枢神经系统异常。越来越多的人有理由相信，即使在没有艾滋病毒或其他病态的情况下，丙型肝炎病毒本身也是神经致病的。丙型肝炎病毒的主要治疗方法是聚乙二醇化干扰素α和利巴韦林(聚乙二醇化干扰素/RBV)。治疗的成功与患者是否能耐受处方剂量和疗程有关。研究尚未集中在患者是否会错过或跳过剂量，这种情况类似于已经在艾滋病毒单一感染中进行了充分研究的情况。鉴于维持丙型肝炎病毒缓解率相对较低(约40%-50%)，并考虑到在持续的一段时间内服用有效的联合药物(大多数将接受48周的治疗)的困难，我们有理由认为，次佳的依从性可能会对治疗失败负有一定责任。这项为期五年的纵向研究试图确定：(1)使用聚乙二醇-干扰素/RBV治疗对神经认知、神经精神和神经成像参数的影响，以及共患艾滋病毒感染改变这种反应的程度；(2)与基线表现相比，获得SVR的参与者是否在统计和临床上表现出显著的神经功能改善；(3)坚持参与者的抗丙型肝炎病毒药物治疗方案对神经功能以及获得持续病毒学反应的可能性的影响程度。我们特别感兴趣的是确定共病艾滋病毒感染如何(或是否)改变与治疗相关的神经变化的表达。我们将招募330名参与者，其中165名是艾滋病毒/丙型肝炎病毒混合感染者，165名是丙型肝炎病毒单一感染者，以获得完成治疗的200名参与者的最终样本。研究参与者将在治疗开始前、治疗开始后12周以及治疗结束后12周接受一系列神经心理和精神测量的评估。嵌套队列将在每个研究时间点接受质子磁共振波谱(MRS)和扩散张量成像(DTI)。我们将使用增长建模和多组路径分析作为主要分析技术。项目简介：人类免疫缺陷病毒(HIV)和丙型肝炎病毒(丙型肝炎病毒)的混合感染越来越被认为是一个紧迫的公共卫生问题，因为在美国，死于丙型肝炎病毒的人数很快将超过死于艾滋病毒的人数。虽然有一些治疗丙型肝炎的药物经常有效，但这些药物也是有毒的，可能会对大脑功能产生不利影响，并导致服药依从性问题。这项研究将确定艾滋病毒和丙型肝炎病毒混合感染如何影响大脑，丙型肝炎病毒治疗如何影响大脑功能，以及坚持服用丙型肝炎病毒药物如何影响治疗反应和神经功能。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。

DESCRIPTION (provided by applicant): 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.