Treatment of HIV-Associated Cognitive Impairment

HIV 相关认知障碍的治疗

• 批准号: 8704774
• 负责人: Ana-Claire Lew Meyer
• 金额: $ 13.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2016-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704774
• 关键词: AIDS Dementia Complex; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adherence; Adult; Adverse effects; Affect; Africa South of the Sahara; Aftercare; Ambulatory Care; Anti-Retroviral Agents; Area; Award; Basic Science; Biomedical Research; Brain; California; Caring; Cerebrospinal Fluid; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical Trials; Cognition; Cohort Studies; Collaborations; Communicable Diseases; Control Groups; Data; Developing Countries; Diagnosis; Diagnostic; Disease; Drug Kinetics; Education; Effectiveness; Enrollment; Environment; Epidemiology; Familiarity; Family; Funding; Future; Goals; HIV; HIV-1; Health; Health Sciences; Home environment; Immunology; Impaired cognition; Impairment; Incidence; Individual; Infection; Inflammation; Institution; International; Kenya; Laboratory Research; Lead; Measures; Mentored Research Scientist Development Award; Mentors; Methods; Neopterin; Nervous system structure; Neuraxis; Neurocognitive; Neurologic; Neurological outcome; Neurologist; Neurology; Neuropsychological Tests; Neuropsychology; Neurovirology; Observational Study; Patient Care; Patients; Penetration; Performance; Pharmaceutical Preparations; Physicians; Plasma; Prevalence; Price; Province; Proxy; RNA; Randomized Controlled Trials; Regimen; Reporting; Research; Research Infrastructure; Research Personnel; Research Training; Resources; Risk; Sampling; San Francisco; Services; Site; Testing; Training; Translational Research; Treatment Effectiveness; Tropical Medicine; Universities; Viral; Work; abstracting; antiretroviral therapy; base; career; clinical research site; cohort; cost effective; design; effective intervention; effective therapy; experience; follow-up; functional status; global health; implementation science; improved; innovation; mortality; multidisciplinary; neurophysiology; neuropsychological; patient oriented; programs; prospective; psychologic; repository; research study; treatment program; virology

Project Summary/Abstract: The Candidate: This is an application for a K01 award for Dr. Ana-Claire Meyer, a neurologist at the University of California, San Francisco. Dr. Meyer is establishing herself as a young investigator focused on patient-oriented clinical research on infectious diseases of the nervous system in resource-limited settings. Dr. Meyer will obtain additional research training through coursework, tutorials and practical experience in the following areas: applying state-of-the-art research and laboratory methods in tropical medicine, neurophysiology, neuropsychology and neurovirology to global health settings; designing and implementing clinical trials; and additional training in implementation science and global health. With this award, she will obtain the didactic training and mentored clinical research experience she needs to establish herself as an independent researcher and successfully compete for R01 funding. This K01 award will enable Dr. Meyer to take the next steps to achieve her long-term career goal: to become a leading researcher developing, evaluating, and implementing innovative and cost-effective interventions to diagnose and treat neurologic conditions in resource limited settings such as sub-Saharan Africa. The Environment: To support her career objectives and research plan, Dr. Meyer has assembled a multidisciplinary mentoring committee comprised of senior clinical investigators who will provide added expertise in conducting clinical, epidemiological, and translational research on HIV-associated neurocognitive disorders within an international collaborative. Her primary mentor is Dr. Richard W. Price, and her co-mentors are Drs. Gretchen Birbeck and Craig Cohen. Her developing country mentor will be Dr. Elizabeth Bukusi. Her home institution, the University of California San Francisco (UCSF), is considered one of the nation's premier health sciences, training, and research centers and has a well-established reputation in biomedical research. The Department of Neurology is a leading academic center dedicated to excellence in patient care, education and research. The HIV Neurology Research Program conducts clinical and basic science research on the effects of HIV on the nervous system and includes active collaborations with clinical HIV, virology and immunology programs. Her international collaborative site, Family AIDS Care and Education Services (FACES), is an HIV/AIDS care and treatment program based in Kenya. FACES currently provides HIV care in 83 facilities in Nyanza Province and Nairobi. As of December 31, 2010, FACES had 96,821 patients cumulatively enrolled with 37,310 patients on ART. FACES clinical sites have previous experience with research studies. In addition, FACES sites are staffed by well-trained clinicians and ancillary staff and have the necessary infrastructure and oversight to complete this study. Research Plan: We estimate that HIV-associated neurocognitive disorders (HAND) may affect nearly 188,000 individuals in Nyanza Province, Kenya, 5.5 million across sub-Saharan Africa, and 8.25 million worldwide. HAND has been associated with poor adherence to antiretroviral therapy (ART) and with higher mortality. Combination ART is the most effective treatment for HAND to date and some studies have suggested that ART with higher penetration into the central nervous system (CNS) lead to improved neurologic outcomes. However, these studies have important limitations and thus there is insufficient evidence to recommend ART with high CNS penetration effectiveness (CPE) for the treatment of HAND. The objective of this application is to determine whether it is important to treat HIV-infected individuals with neurocognitive disorders with ART with high CPE. Because of limited ART choices in Kenya, we will be able to directly compare the effects of specific ART regimens thus avoiding the limitations of prior studies. The central hypothesis is that, among individuals with HAND, ART with high CPE lead to improved neurologic outcomes as compared to ART with low CPE. We will enroll a prospective observational cohort of 200 HIV-infected ART- na¿ve adults with HIV-associated cognitive impairment. Aim 1: To determine the effect of common ART regimens with different CNS pharmacokinetics on the neuro-psychological performance of ART-na¿ve HIV infected adults with cognitive impairment in western Kenya Over a follow-up period of 48 weeks, we will determine the effect of four ART regimens on three NP measures: a composite score, the QNPZ-4, and level of impairment using common diagnostic criteria. Aim 2: To determine the effect of common ART regimens with different CNS pharmacokinetics on viral replication and inflammation in the cerebrospinal fluid (CSF) of ART-na¿ve HIV infected adults with cognitive impairment in western Kenya In a sub-sample of 100 individuals, we will determine the effect of ART regimens on: (1) CSF HIV-1 RNA; (2) CSF:plasma HIV-1 RNA ratio; (3) CSF WBC count; (4) CSF neopterin. We will also create a unique repository of samples for future collaborative studies. Aim 3: To determine whether there is a practice effect on the neuropsychological test battery We will re-administer our NP battery to 100 HIV un-infected individuals who we have previously studied. These specific aims logically build toward an R01 to determine the effect of ART on combined systemic and neurologic outcomes in cognitively impaired individuals in a randomized controlled trial.

项目摘要/摘要： 候选人：这是 Ana-Claire Meyer 博士的 K01 奖项申请，她是该大学的神经科医生。 迈耶博士是加州大学旧金山分校的一名年轻研究员，专注于研究领域。 资源有限环境中以患者为导向的神经系统传染病临床研究。 迈耶将通过课程、教程和实践经验获得额外的研究培训 以下领域：在热带医学中应用最先进的研究和实验室方法， 全球卫生环境的神经生理学、神经心理学和神经病毒学的设计和实施； 凭借这一奖项，她将获得临床试验以及实施科学和全球健康方面的额外培训。 获得她所需的教学培训和指导的临床研究经验，以将自己打造成一名 独立研究员并成功竞争 R01 资助将使 Meyer 博士能够 采取接下来的步骤来实现她的长期职业目标：成为一名领先的研究人员，开发、 评估和实施创新且具有成本效益的干预措施来诊断和治疗神经系统疾病 撒哈拉以南非洲等资源有限地区的条件。 环境：为了支持她的职业目标和研究计划，迈耶博士组建了一个 由高级临床研究人员组成的多学科指导委员会将提供额外的帮助 HIV相关神经认知的临床实施、流行病学和转化研究方面的专业知识 她的主要导师是 Richard W. Price 博士，以及她的共同导师。 格雷琴·伯贝克 (Gretchen Birbeck) 博士和克雷格·科恩 (Craig Cohen) 博士是她的发展中国家导师。 她的母校加州大学旧金山分校 (UCSF) 被认为是美国最顶尖的大学之一 国家首屈一指的健康科学、培训和研究中心，并在医疗保健领域享有盛誉 神经病学系是一个致力于卓越的生物医学研究中心。 艾滋病毒神经病学研究项目开展临床和基础研究。 关于艾滋病毒对神经系统影响的科学研究，包括与临床的积极合作 她的艾滋病毒、病毒学和免疫学项目，家庭艾滋病护理和教育。 服务 (FACES) 是 FACES 目前在肯尼亚提供的一项艾滋病毒/艾滋病护理和治疗计划。 截至 2010 年 12 月 31 日，FACES 已在尼安萨省和内罗毕的 83 个机构提供艾滋病毒护理服务。 FACES 临床中心累计登记的 37,310 名患者有过相关经验。 此外，FACES 站点还配备了训练有素的超级明星和辅助人员， 拥有完成这项研究所需的基础设施和监督。 研究计划：我们估计 HIV 相关神经认知障碍 (HAND) 可能影响近 肯尼亚尼安萨省有 188,000 人，撒哈拉以南非洲地区有 550 万人，还有 825 万人 在世界范围内，HAND 与抗逆转录病毒治疗 (ART) 依从性差和较高的依从性有关。 联合 ART 是迄今为止最有效的 HAND 治疗方法，一些研究表明。 表明 ART 对中枢神经系统 (CNS) 具有更高的渗透性，可改善神经功能 然而，这些研究有很大的局限性，因此没有足够的证据。 推荐具有高中枢神经系统渗透效力（CPE）的 ART 治疗 HAND。 该应用程序旨在确定用神经认知功能治疗 HIV 感染者是否重要 由于肯尼亚的 ART 选择有限，我们将能够直接治疗患有高 CPE 的 ART 疾病。 比较特定 ART 方案的效果，从而避免先前研究的局限性。 假设是，在患有 HAND 的个体中，具有高 CPE 的 ART 可以改善神经系统结果，如下所示： 与低 CPE 的 ART 相比，我们将招募 200 名感染 HIV 的 ART 患者组成的前瞻性观察队列。 呐5 名患有 HIV 相关认知障碍的成年人。 目标 1：确定具有不同 CNS 药代动力学的常见 ART 方案对 ART-na的神经心理表现¿肯尼亚西部有 5 名艾滋病毒感染成年人患有认知障碍 在 48 周的随访期内，我们将确定四种 ART 方案对三项 NP 指标的影响： 使用通用诊断标准的综合评分、QNPZ-4 和损伤程度。 目标 2：确定具有不同 CNS 药代动力学的常见 ART 方案对病毒的影响 ART-na 脑脊液 (CSF) 中的复制和炎症患有认知功能障碍的艾滋病毒感染者 肯尼亚西部的损害 在 100 名个体的子样本中，我们将确定 ART 方案对以下方面的影响：(1) CSF HIV-1 RNA；(2) CSF：血浆 HIV-1 RNA 比率；（3）CSF WBC 计数；（4）CSF 新蝶呤。 供未来合作研究的样本。 目标3：确定神经心理学测试电池是否有练习效果 我们将对 100 名我们之前研究过的未感染 HIV 的个体重新使用我们的 NP 电池。 这些具体目标在逻辑上建立在 R01 的基础上，以确定 ART 对综合系统和疾病的影响。 随机对照试验中认知障碍患者的神经学结果。