Extension of a longitudinal cognitive and brain imaging study of early-treated perinatally HIV infected children through adolescence

对早期治疗的围产期艾滋病毒感染儿童至青春期的纵向认知和脑成像研究的扩展

• 批准号: 10013263
• 负责人: Barbara Laughton
• 金额: $ 56.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10013263
• 关键词: 3-Dimensional; Acquired Immunodeficiency Syndrome; Adolescence; Adolescent; Adult; Affect; Affective; Africa South of the Sahara; African; Age; Age-Months; Anti-Retroviral Agents; Area; Attention; Behavior; Behavior Control; Behavioral; Birth; Brain; Brain imaging; Child; Childhood; Clinical; Clinical Data; Clinical Research; Clinical Trials Network; Clinical assessments; Cognition; Cognitive; Collaborations; Communities; Country; Data; Development; Diffusion; Disease Management; Emotional; Epidemic; Exhibits; Family; Functional Imaging; Functional Magnetic Resonance Imaging; General Hospitals; Generations; Growth; HIV; HIV Infections; HIV Seropositivity; HIV antiretroviral; HIV therapy; Home environment; Image; Imaging Techniques; Immunologics; Impaired cognition; Impulsive Behavior; Impulsivity; Infection; Infrastructure; International; International Maternal Pediatric Adolescent AIDS Clinical Trials; Investments; Knowledge; Limbic System; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Massachusetts; Memory; Methods; Motion; Neurocognitive; Perinatal; Population; Prefrontal Cortex; Protocols documentation; Public Policy; Research; Resources; Rest; Rewards; Risk; Risk-Taking; Schools; Social Change; South Africa; Spectrum Analysis; Structure; System; Teenagers; Therapy trial; Time; United States; United States National Institutes of Health; Universities; Viral; Visit; Youth; advanced disease; antiretroviral therapy; base; cognitive ability; cognitive development; cognitive testing; cohort; critical period; early childhood; emotional functioning; executive function; follow-up; hemodynamics; high risk; imaging study; improved; infancy; magnetic resonance spectroscopic imaging; morphometry; myelination; neurobehavioral; neurodevelopment; neuroimaging; peer; perinatal HIV; programs; recruit; resilience; response; sociodemographics; spectroscopic imaging; synaptic pruning; tool; treatment strategy; vaccine trial; young adult; young woman

Project Summary While the Eastern and Southern African region is home to 6.2% of the world's population, more than half the world's HIV infected people live here. The biggest epidemic is in South Africa, with 7.2 million people living with HIV. Although the rate of new infections has decreased dramatically worldwide from the peak in 1996, one third (270,000) of new infections in Sub-Saharan Africa last year occurred in South Africa. Young adults are disproportionately affected, with 37% of new infections in South Africa occurring in young women between the ages of 15 and 24. Youth are similarly more likely to be infected in the United States. Adolescence represents a critical period of brain maturation, with ongoing myelination, cortical growth and synaptic pruning. Gradual and differential maturation of the limbic system and prefrontal cortex modulates reward and affective behavior, and executive control. HIV infection and ART present further challenges to neurodevelopment and resilience in this vulnerable stage of development. Cognitive impairment in HIV infected children has been demonstrated in several domains, including memory, attention, and general intellectual functioning. There is an urgent need for research on the longitudinal trajectory of neurodevelopment in perinatally-acquired HIV infected (PHIV+) children and adolescents, especially in resource-limited countries. In this study, we will extend our longitudinal follow-up of two extremely well-characterized PHIV+ cohorts, adding neuroimaging and cognitive assessments at 14 and 16 years, and continuing 6-monthly clinical visits. The study will include 80 PHIV+ children from the “Children with HIV early antiretroviral therapy” (CHER) trial, originally supported by the Comprehensive International Program for Research on AIDS in South Africa (CIPRA-SA). Controls were recruited by a CIPRA-SA supported interlinking vaccine trial. This cohort has been followed clinically since birth, and with cognitive assessments and neuroimaging from the age of 5. The cohort incorporates children who commenced ART before 12 weeks, and children whose treatment was delayed until immunological criteria were met. We will also include 30 PHIV+ children from the IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials Network) P1060 and P1104S studies who started ART at 2 to 36 months after exhibiting relatively advanced disease, and uninfected controls from the same cohort. The Cape Universities Body Imaging Centre (CUBIC) houses a state-of-the-art research-dedicated Siemens 3 T Skyra MRI scanner optimized for brain imaging, and unique in sub-Saharan Africa. We have developed the capability for advanced brain morphometry, spectroscopy, diffusion tensor and functional imaging. This project builds on a successful decade-long collaboration between Dr. Ernesta Meintjes (University of Cape Town), Dr. Barbara Laughton (Stellenbosch University) and Dr. André van der Kouwe (Massachusetts General Hospital). The project will build capacity including analysis methods for dynamic functional imaging and advanced spectroscopic imaging techniques.

项目概要 虽然东部和南部非洲地区人口占世界人口的 6.2%，但一半以上 世界上艾滋病毒感染者居住在这里，疫情最严重的是南非，有 720 万人居住。 尽管全球新感染率较 1996 年的峰值大幅下降，但 去年撒哈拉以南非洲地区的三分之一（270,000）新感染病例发生在南非。 受到的影响尤为严重，南非 37% 的新感染病例发生在年轻女性身上 15 岁和 24 岁之间。在美国，青少年同样更容易被感染。 青春期是大脑成熟的关键时期，髓鞘形成、皮质生长和 边缘系统和前额皮质的逐渐和差异性成熟进行调节。 奖励和情感行为、执行控制以及艾滋病毒感染和抗逆转录病毒疗法给我们带来了进一步的挑战。 HIV感染者在这个脆弱的发展阶段的神经发育和恢复能力。 儿童在多个领域都得到了证明，包括记忆力、注意力和一般智力 迫切需要研究神经发育的纵向轨迹。 围产期感染艾滋病毒（PHIV+）的儿童和青少年，特别是在资源有限的国家。 在这项研究中，我们将延长对两个特征极其明确的 PHIV+ 队列的纵向随访， 在 14 岁和 16 岁时增加神经影像和认知评估，并持续每 6 个月进行一次临床就诊。 该研究将包括来自“艾滋病毒儿童早期抗逆转录病毒治疗”（CHER）试验的 80 名 PHIV+ 儿童， 最初由南非艾滋病综合国际研究计划支持 (CIPRA-SA) 该队列是由 CIPRA-SA 支持的互连疫苗试验招募的。 从出生起就进行临床随访，并从 5 岁开始进行认知评估和神经影像学检查。 包括在 12 周之前开始 ART 的儿童，以及治疗延迟至 我们还将纳入来自 IMPAACT（国际）的 30 名 PHIV+ 儿童。 2 岁开始接受 ART 的孕产妇、儿科青少年艾滋病临床试验网络）P1060 和 P1104S 研究 表现出相对晚期疾病后至 36 个月，以及来自同一队列的未感染对照。 开普大学身体成像中心 (CUBIC) 拥有最先进的研究专用中心 西门子 3 T Skyra 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独一无二。 开发了先进的大脑形态测量、光谱、扩散张量和功能的能力 该项目建立在 Ernesta Meintjes 博士长达十年的成功合作基础上。 （开普敦大学）、Barbara Laughton 博士（斯泰伦博斯大学）和 André van der Kouwe 博士 （麻省总医院）该项目将建设能力，包括动态分析方法。 功能成像和先进的光谱成像技术。