Longitudinal Neuroimaging and Cognitive Study of HIV-Infected Children

HIV 感染儿童的纵向神经影像和认知研究

• 批准号: 8256461
• 负责人: Barbara Laughton
• 金额: $ 54.99万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8256461
• 关键词: 5 year old; 9 year old; AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Addendum; Affect; Africa South of the Sahara; African; Age; Algorithms; Allegra; Anesthesia procedures; Anisotropy; Anti-Retroviral Agents; Aventyl; Basal Ganglia; Birth; Boston; Brain; Brain imaging; CD4 Lymphocyte Count; Cessation of life; Child; Childhood; Choline; Chronic; Clinical; Clinical Research; Cognitive; Collaborations; Communicable Diseases; Control Groups; Creatine; Data; Data Analyses; Developing Countries; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Early treatment; Environment; Funding; General Hospitals; HIV; HIV Infections; HIV diagnosis; High Performance Computing; Home environment; Housing; Image; Image Analysis; Imaging Techniques; Imaging technology; Improve Access; Infant Mortality; Inositol; International; Laboratories; Life; Magnetic Resonance Imaging; Massachusetts; Methods; Motion; N-acetylaspartate; National Institute of Allergy and Infectious Disease; Neuraxis; Neuropsychological Tests; Participant; Penetration; Plasma; Population; Protocols documentation; Recruitment Activity; Research; Research Infrastructure; Residual state; Resolution; Resources; Risk; Science; Sedation procedure; South Africa; Spectrum Analysis; Structure; Students; Techniques; Technology; Testing; Thick; Time; Tissues; Training; Universities; Vaccines; Validation; Viral Load result; Virus; Visit; antiretroviral therapy; arm; bioimaging; brain metabolism; clinical practice; cohort; computing resources; fetal; gray matter; improved; insight; longitudinal analysis; meetings; mental development; morphometry; neurodevelopment; neuroimaging; neuropsychological; programs; relating to nervous system; sound; standard care; treatment strategy; visual-motor integration; white matter

DESCRIPTION (provided by applicant): While sub-Saharan Africa is home to 10% of the world's population, 90% of the world's HIV-infected children live in the region. The majority of these (16% or 280,000) live in South Africa, where HIV/AIDS accounts for 57% of deaths in children below 5 years of age. With improving access to antiretroviral treatment (ART), the disease is changing from fatal to chronic. However, central nervous system penetration by ART is limited and the brain is a reservoir for the virus, with dramatic consequences to the developing fetal/child brain. The "Children with HIV early antiretroviral therapy" (CHER) project is supported by the Comprehensive International Program for Research on AIDS in South Africa (CIPRA-SA), and has been following a cohort of children born with HIV. Controls were recruited by an interlinking vaccine trial supported by CIPRA-SA. This is a unique and extremely well characterized cohort of children in three treatment arms in which ART (1) was delayed until immunological/clinical criteria were met, (2) commenced before 12 weeks and was interrupted after 40 weeks and (3) commenced before 12 weeks and was interrupted after 96 weeks. After two years, results showed that early HIV diagnosis and ART reduced early infant mortality by 76% and HIV progression by 75%. In an addendum to the study, Dr. Barbara Laughton performed comprehensive neuropsychological testing on the Cape Town participants. The study will end after all children reach 5 years of age in June 2011. Studies of neurodevelopment in children with HIV in developing countries are rare and brain imaging studies of young children with HIV anywhere in the world are also scarce. Longitudinal brain imaging studies in children with HIV are non-existent. We have completed cognitive testing and MR imaging in a subset of the 210 children in the Cape Town branch of the CHER cohort at the age of 5 years. Imaging was done at the Cape Universities Brain Imaging Center (CUBIC), using motion-corrected brain morphometry, spectroscopy and diffusion tensor imaging protocols that were developed jointly by our groups. This facility houses a state- of-the-art research-dedicated Siemens 3 T Allegra MRI scanner optimized for brain imaging and is unique in sub-Saharan Africa. In this project, we will follow the children further with comprehensive neuropsychological testing and brain imaging at the ages of 7 and 9 years. The multi-time point longitudinal data will give us greater power to assess how cognitive and anatomical development proceeds in healthy children between 5 and 9 years and how this is affected by HIV infection and treatment with ART. We hope that our findings will help to guide treatment even in resource-poor environments where imaging may be unavailable. This project builds on a successful collaboration between Dr. Barbara Laughton (Stellenbosch University), Dr. Ernesta Meintjes (University of Cape Town) and Dr. Andri van der Kouwe (Massachusetts General Hospital). The project will build capacity including analysis methods for longitudinal data and advanced image acquisition techniques in young children, without the risk of sedation or anesthesia. PUBLIC HEALTH RELEVANCE: The study builds on an existing collaboration between the Universities of Stellenbosch and Cape Town and the MGH to develop a data analysis infrastructure, collect, analyze and interpret pediatric data using MRI. We aim to establish the effects of HIV and ART in children and guide treatment strategies in resource-limited settings.

描述（由申请人提供）：虽然撒哈拉以南非洲地区人口占世界人口的 10%，但世界上 90% 的艾滋病毒感染儿童生活在该地区。其中大多数（16% 或 280,000 人）生活在南非，该国 5 岁以下儿童死亡人数中 57% 是由艾滋病毒/艾滋病造成的。随着抗逆转录病毒治疗（ART）的普及，这种疾病正在从致命转变为慢性。然而，抗逆转录病毒疗法对中枢神经系统的渗透有限，而且大脑是病毒的储存库，对发育中的胎儿/儿童大脑造成严重后果。 “感染艾滋病毒的儿童早期抗逆转录病毒治疗”（CHER）项目得到了南非艾滋病综合国际研究计划（CIPRA-SA）的支持，并一直在跟踪一群出生时感染艾滋病毒的儿童。对照是通过 CIPRA-SA 支持的一项互连疫苗试验招募的。这是三个治疗组中独特且特征极其明确的儿童队列，其中 ART (1) 延迟直至满足免疫学/临床标准，(2) 在 12 周前开始，并在 40 周后中断，(3) 在12周，96周后中断。两年后，结果显示，早期艾滋病毒诊断和抗逆转录病毒治疗将早期婴儿死亡率降低了 76%，艾滋病毒进展降低了 75%。在该研究的附录中，芭芭拉·劳顿博士对开普敦的参与者进行了全面的神经心理学测试。该研究将于 2011 年 6 月所有儿童年满 5 岁后结束。对发展中国家艾滋病毒感染儿童神经发育的研究很少，对世界各地艾滋病毒感染幼儿的脑成像研究也很少。对艾滋病毒儿童的纵向脑成像研究尚不存在。我们已经对 CHER 队列开普敦分支的 210 名 5 岁儿童中的一部分完成了认知测试和 MR 成像。成像是在开普大学脑成像中心（CUBIC）进行的，使用了我们小组共同开发的运动校正脑形态测量、光谱学和扩散张量成像协议。该设施拥有最先进的研究专用西门子 3 T Allegra MRI 扫描仪，该扫描仪针对脑成像进行了优化，在撒哈拉以南非洲地区是独一无二的。在这个项目中，我们将进一步跟踪7岁和9岁儿童的全面神经心理学测试和脑成像。多时间点纵向数据将使我们更有能力评估 5 至 9 岁健康儿童的认知和解剖学发育如何进行，以及 HIV 感染和 ART 治疗对其有何影响。我们希望我们的研究结果将有助于指导治疗，即使是在无法进行成像的资源匮乏的环境中。 该项目建立在 Barbara Laughton 博士（斯泰伦博斯大学）、Ernesta Meintjes 博士（开普敦大学）和 Andri van der Kouwe 博士（马萨诸塞州总医院）之间的成功合作基础上。该项目将培养幼儿的能力，包括纵向数据分析方法和先进的图像采集技术，而无需镇静或麻醉的风险。 公共健康相关性：该研究建立在斯泰伦博斯大学和开普敦大学与麻省总医院之间现有合作的基础上，开发数据分析基础设施，使用 MRI 收集、分析和解释儿科数据。我们的目标是确定艾滋病毒和抗逆转录病毒治疗对儿童的影响，并指导资源有限环境中的治疗策略。