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

HIV/HCV 感染抗 HCV 治疗前后的神经行为缺陷

• 批准号: 8287090
• 负责人: CHARLES H HINKIN
• 金额: $ 56.42万
• 依托单位: BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8287090
• 关键词: Achievement; Adherence; Adult; Adverse effects; Affect; Aftercare; Alcohol or Other Drugs use; Antiviral Agents; Antiviral Therapy; Attenuated; Autoimmune Process; Autopsy; Basal Ganglia; Brain; Brain region; Cessation of life; Cognition; Cognitive; Combination Medication; Congenital neurologic anomalies; Corpus striatum structure; Data; Detection; Diffusion Magnetic Resonance Imaging; Disease; Disease remission; Dose; Drug Formulations; Enrollment; Exhibits; Functional disorder; Genotype; Growth; HIV; Healthcare; Hepatic Encephalopathy; Hepatitis C; Hepatitis C virus; Highly Active Antiretroviral Therapy; Impaired cognition; Impairment; Infection; Injecting drug user; Intention; Interferons; Lead; Light; Link; Liver; Liver Failure; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measures; Mediating; Mental Depression; Modeling; Mono-S; Nervous System Physiology; Neuraxis; Neurocognitive; Neurophysiology - biologic function; Outcome; Participant; Patients; Pattern; Pegylated Interferon Alfa; Performance; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Physicians; Positioning Attribute; Predisposition; Process; Protons; Public Health; Publishing; Regimen; Reporting; Research; Ribavirin; Risk; Sampling; Series; Severities; Staging; Stroke; Substance abuse problem; Symptoms; System; Techniques; Thrombosis; Time; Treatment Failure; Treatment Protocols; United States; Vasculitis; Viral; Virus; Virus Diseases; anti-hepatitis C; base; clinically significant; cohort; dosage; experience; frontal lobe; health belief; improved; interest; interferon therapy; medication compliance; neurobehavioral; neuroimaging; neuropsychiatry; neuropsychological; novel; prospective; response; success; therapy adherence; therapy duration; treatment adherence; treatment duration; treatment effect; treatment response; viral RNA

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.

此应用程序响应：PA-07-089 HIV感染中枢神经系统和 部分响应：PA-07-338艾滋病毒治疗依从性研究。与日本血吸虫病合并感染 人类免疫缺陷病毒(HIV)和丙型肝炎病毒(HCV)是一种新兴的保健 令人担忧，因为美国大约三分之一的艾滋病毒感染者是联合感染的 感染了丙型肝炎病毒。感染艾滋病毒和丙型肝炎病毒可引起一系列认知、精神和中枢 神经系统异常。越来越多的人有理由相信丙型肝炎病毒，即使在 没有艾滋病毒或其他病态，本身就是神经致病。主要的治疗方法是 丙型肝炎病毒是聚乙二醇化的干扰素α和利巴韦林(聚乙二醇化干扰素/RBV)。治疗的成功与 患者是否能耐受规定的剂量和疗程。研究尚未完成 重点关注患者是否会错过或跳过服药，这与之前的情况类似 研究艾滋病毒单一感染。鉴于维持丙型肝炎病毒缓解率相对较低 (约40%-50%)，并考虑到服用有效的药物组合治疗 持续一段时间(大多数人将接受48周的治疗)，有理由认为 次优的依从性可能会为治疗失败分担一些责任。 这项为期五年的纵向研究试图确定：(1)使用聚乙二醇治疗的影响- 干扰素/RBV对神经认知、神经精神病学和神经影像学参数的影响 哪些共病的HIV感染改变了这种反应；(2)获得SVR的参与者 在统计和临床上表现出显著的神经功能改善 基线表现和(3)参与者对抗丙型肝炎药物的坚持程度 治疗方案影响神经功能以及获得持续病毒学的可能性 回应。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。 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 艾滋病毒/丙型肝炎病毒混合感染者和165名丙型肝炎病毒单一感染者，以获得最终样本 200名完成治疗的参与者。研究参与者将接受一系列评估 开始治疗前、治疗12周后的神经心理和精神测量 治疗已经开始，然后在治疗完成后12周。一个嵌套的队列 将在以下时间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。我们将使用增长建模和多组路径分析作为 主要的分析技术。项目简介：与人类免疫缺陷病毒(艾滋病毒)和丙型肝炎混合感染 病毒(丙型肝炎病毒)日益被认为是一个紧迫的公共卫生问题，因为 在美国，死于丙型肝炎的人数很快将超过死于艾滋病毒的人数。虽然有 治疗丙型肝炎病毒的药物通常是有效的，这些药物也是有毒的，可能会对 影响大脑功能，并导致服药依从性问题。这项研究将确定如何 同时感染艾滋病毒和丙型肝炎病毒会影响大脑，丙型肝炎病毒的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。