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：这是为Ana-Claire Meyer博士申请K01奖的申请， 加利福尼亚大学，旧金山。迈耶博士正在建立自己的年轻调查员，专注于 在资源有限的环境中，针对神经系统传染病的临床研究。博士 迈耶将通过课程，教程和实践经验获得其他研究培训 以下领域：在热带医学中应用最先进的研究和实验室方法， 全球健康环境的神经生理学，神经心理学和神经病毒学；设计和实施 临床试验；以及实施科学和全球健康方面的其他培训。有了这个奖项，她将 获得教学培训并修补她所需的临床研究经验 独立研究人员并成功竞争R01资金。该K01奖将使Meyer博士能够 采取下一步实现她的长期职业目标：成为发展的主要研究人员， 评估并实施创新和具有成本效益的干预措施来诊断和治疗神经系统 资源有限的环境，例如撒哈拉以南非洲。 环境：为了支持她的职业目标和研究计划，迈耶博士召集了 多学科指导委员会完成了高级临床研究人员的完成 在进行临床，流行病学和翻译有关HIV相关神经认知的研究方面的专业知识 国际协作中的疾病。她的主要导师是理查德·W·普莱斯（Richard W. 是博士。格蕾琴·比贝克（Gretchen Birbeck）和克雷格·科恩（Craig Cohen）。她的发展中国家导师将是伊丽莎白·布库西（Elizabeth Bukusi）博士。 她的家庭机构，加利福尼亚大学旧金山大学（UCSF），被认为是 国家的主要健康科学，培训和研究中心，并在 生物医学研究。神经病学系是一个领先的学术中心，致力于卓越 患者护理，教育和研究。 HIV神经病学研究计划进行临床和基本 科学研究艾滋病毒对神经系统的影响，包括与临床的积极合作 艾滋病毒，病毒学和免疫学计划。她的国际合作网站，家庭艾滋病护理和教育 服务（面孔）是肯尼亚的艾滋病毒/艾滋病护理和治疗计划。面孔当前提供 Nyanza省和内罗毕的83个设施中的HIV护理。截至2010年12月31日，面孔有96,821 患者累积入学37,310名ART患者。面孔临床网站有以前的经验 研究研究。此外，面孔网站由训练有素的临床医生和辅助人员组成， 拥有必要的基础设施和监督来完成这项研究。 研究计划：我们估计与HIV相关的神经认知障碍（手）几乎可能影响 肯尼亚Nyanza省的188,000个人，撒哈拉以南非洲的550万人和825万 全世界。手与抗逆转录病毒疗法（ART）的依从性不佳有关，并且较高 死亡。联合艺术是迄今为止手工的最有效治疗方法，一些研究已 提出渗透到中枢神经系统（CNS）的较高的艺术导致神经系统的改善 结果。但是，这些研究具有重要的局限性，因此没有足够的证据 推荐的具有高CNS渗透效果（CPE）的艺术品用于治疗手。目的 该应用是为了确定治疗具有神经认知的HIV感染者是否重要 具有高CPE的艺术疾病。由于肯尼亚的艺术选择有限，我们将能够直接 比较特定艺术方案的影响，从而避免了先前研究的局限性。中央 假设是，在有手的人中，具有高CPE的艺术导致神经系统结局的改善，因为 与CPE低的艺术相比。我们将招收200个HIV感染艺术的前瞻性观察队列 NA¿VE成年人患有HIV相关的认知障碍。 目的1：确定具有不同CNS药代动力学的常见艺术方案对 肯尼亚西部的Art-na ve HIV感染的成年人的神经心理表现 在48周的随访期内，我们将确定四种ART方案对三种NP措施的影响： 使用常见诊断标准的综合评分，QNPZ-4和损害水平。 目标2：确定不同CNS药代动力学对病毒的普通艺术方案的影响 脑脊液（CSF）的复制和炎症感染了艾滋病毒的成年人 肯尼亚西部的损害 在100个个体的子样本中，我们将确定艺术方案对：（1）CSF HIV-1 RNA的影响； （2） CSF：血浆HIV-1 RNA比率； （3）CSF WBC计数； （4）CSF Neopterin。我们还将创建一个独特的存储库 样本的未来协作研究。 目标3：确定是否对神经心理测试电池有练习效果 我们将把NP电池重新限制在以前研究的100个未感染的HIV未感染的人。 这些特定目标从逻辑上建立在R01上，以确定艺术对系统合并的影响和 在随机对照试验中，认知受损的个体的神经系统结局。