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: 7681063
• 负责人: CHARLES H HINKIN
• 金额: $ 60.17万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7681063
• 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; 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; Reporting; Research; Ribavirin; Risk; Sampling; Series; Severities; Staging; Stroke; Symptoms; System; Techniques; Thrombosis; Time; Treatment Failure; Treatment Protocols; United States; Vasculitis; Viral; Virus; Virus Diseases; anti-hepatitis C; base; clinically significant; cohort; depression; 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

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.

描述（由申请人提供）：本申请响应 PA-07-089 HIV 中枢神经系统感染，并部分响应：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 (HCV) 的双重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者同时感染了丙型肝炎病毒。 HIV 和 HCV 感染可导致一系列认知、精神和中枢神经系统异常。人们越来越有理由相信，即使没有艾滋病毒或其他疾病，丙型肝炎病毒本身也具有神经致病性。 HCV 的主要治疗方法是聚乙二醇干扰素 α 和利巴韦林 (PEG-IFN/RBV)。治疗的成功与患者是否能够耐受规定的剂量和治疗持续时间有关。研究尚未集中于患者是否可能错过或跳过剂量，这与艾滋病毒单一感染中已得到充分研究的情况类似。鉴于 HCV 持续缓解率相对较低（约 40-50%），且难以持续服用有效的药物组合（大多数将接受 48 周的治疗），因此可以合理地假设，不理想的依从性可能对治疗失败负有部分责任。这项为期五年的纵向研究旨在确定：(1) PEG-IFN/RBV 治疗对神经认知、神经精神和神经影像学参数的影响，以及共病 HIV 感染改变这种反应的程度； (2) 与基线表现相比，实现 SVR 的参与者是否表现出神经功能在统计和临床上显着改善，以及 (3) 参与者坚持抗 HCV 药物治疗方案对神经功能以及获得持续病毒学应答的可能性的影响程度。我们特别感兴趣的是确定共病 HIV 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 名 HIV/HCV 双重感染者和 165 名 HCV 单一感染者，以获得完成治疗的 200 名参与者的最终样本。研究参与者将在开始治疗前、治疗开始后 12 周以及治疗完成后 12 周接受一系列神经心理学和精神病学测量。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) 和丙型肝炎病毒 (HCV) 的双重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，丙型肝炎病毒 (HCV) 造成的死亡人数将很快超过艾滋病毒 (HIV) 造成的死亡人数。虽然有些治疗 HCV 的药物通常有效，但这些药物也有毒，可能对大脑功能产生不利影响，并导致药物依从性问题。这项研究将确定 HIV 和 HCV 共同感染如何影响大脑、HCV 治疗如何影响大脑功能，以及 HCV 药物的依从性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治疗反应。