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.

项目摘要 虽然东部和南部非洲地区拥有世界6.2%的人口，但超过一半的人 世界上感染艾滋病毒的人生活在这里。最大的疫情发生在南非，有720万人 艾滋病毒携带者。尽管世界范围内的新感染率从1996年的峰值大幅下降，但有一个 去年撒哈拉以南非洲新增感染病例中有三分之一(27万例)发生在南非。年轻人是 受影响不成比例，南非37%的新感染病例发生在 年龄分别为15岁和24岁。同样，在美国，年轻人更有可能被感染。 青春期代表着大脑成熟的关键时期，伴随着不断的髓鞘形成、皮质生长和 突触修剪。边缘系统和前额叶皮质的逐渐和不同的成熟调节 奖励和情感行为，以及执行控制。艾滋病毒感染和抗逆转录病毒治疗对 在这个脆弱的发展阶段，神经发展和韧性。HIV感染者的认知功能障碍 儿童已经在几个领域得到了证明，包括记忆力、注意力和一般智力 功能正常。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+)儿童和青少年，特别是在资源有限的国家。 在这项研究中，我们将扩展我们对两个特征非常好的PHIV+队列的纵向随访， 在14岁和16岁时增加神经成像和认知评估，并继续每6个月进行一次临床就诊。 这项研究将包括80名艾滋病病毒携带者儿童早期抗逆转录病毒治疗(CHER)试验中的PHIV阳性儿童， 最初由南非艾滋病综合国际研究计划资助 (CIPRA-SA)。对照由CIPRA-SA支持的连锁疫苗试验招募。这群人一直是 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成像。 纳入在12周前开始接受抗逆转录病毒治疗的儿童，以及治疗推迟到 符合免疫学标准。我们还将包括来自IMPAACT(国际)的30名PHIV+儿童 母体青少年艾滋病临床试验网络)P1060和P1104S研究，从2岁开始抗逆转录病毒治疗 至36个月后表现出相对晚期的疾病，而未感染的对照组来自同一队列。 开普敦大学身体成像中心(CUBIC)拥有一家致力于最先进研究的 西门子3T Skyra核磁共振扫描仪针对脑成像进行了优化，在撒哈拉以南非洲地区独一无二。我们有 开发高级脑形态测量、光谱、扩散张量和功能的能力 成像。该项目建立在Ernesta Meintjes博士之间长达十年的成功合作基础上 Barbara Laughton博士(StellenBosch大学)和Andrévan der Kouwe博士(开普敦大学) (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。