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: 8487425
• 负责人: Barbara Laughton
• 金额: $ 43.78万
• 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/8487425
• 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.

描述（由申请人提供）：虽然撒哈拉以南非洲是世界人口的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28万）生活在南非，艾滋病毒/艾滋病占5岁以下儿童死亡的57%。随着获得抗逆转录病毒治疗的机会增加，这种疾病正在从致命性转变为慢性病。然而，ART对中枢神经系统的渗透是有限的，大脑是病毒的储存库，对发育中的胎儿/儿童大脑产生严重后果。 “感染艾滋病毒的儿童早期抗逆转录病毒治疗”项目得到了南非艾滋病综合国际研究方案的支持，并一直在跟踪一组出生时感染艾滋病毒的儿童。通过CIPRA-SA支持的互连疫苗试验招募对照。这是一个独特且特征非常明确的儿童队列，分为三个治疗组，其中ART（1）延迟至符合免疫学/临床标准，（2）在12周前开始，40周后中断，（3）在12周前开始，96周后中断。两年后，结果显示，早期艾滋病毒诊断和ART将早期婴儿死亡率降低了76%，艾滋病毒进展降低了75%。在这项研究的附录中，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。这项研究将在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，对世界上任何地方艾滋病毒感染幼儿的脑成像研究也很少。对艾滋病毒感染儿童的纵向脑成像研究尚不存在。我们对CHER队列开普敦分支的210名5岁儿童的一个子集进行了认知测试和MR成像。成像是在开普敦大学脑成像中心（CUBIC）进行的，使用我们小组共同开发的运动校正脑形态测量，光谱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，针对大脑成像进行了优化，在撒哈拉以南非洲地区是独一无二的。在这个项目中，我们将在7岁和9岁时对儿童进行全面的神经心理学测试和大脑成像。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发育如何进行，以及艾滋病毒感染和ART治疗如何影响这些发育。我们希望我们的研究结果将有助于指导治疗，即使在资源匮乏的环境中，成像可能无法获得。 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货车der Kouwe博士（马萨诸塞州总医院）之间成功合作的基础上。该项目将建立能力，包括纵向数据分析方法和幼儿先进的图像采集技术，没有镇静或麻醉的风险。