Cape Town Adolescent Antiretroviral Cohort- Substance, Imaging, Mental Health (CTAAC-SIM)

开普敦青少年抗逆转录病毒队列 - 物质、影像、心理健康 (CTAAC-SIM)

基本信息

批准号：
10649665
负责人：
Jacqueline Hoare
金额：
$ 35.9万
依托单位：
UNIVERSITY OF CAPE TOWN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10649665
关键词：
21 year old Adolescence Adolescent Adult Affect Affective Africa South of the Sahara Age Alcohols Anti-Retroviral Agents Award Behavior Control Behavioral Birth Brain Brain imaging CD4 Antigens Cannabis Cells Central Nervous System Central Nervous System Diseases Child Chronic Cognitive Collaborations Consumption DNA Data Dedications Development Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Progression Emotional Epidemic Evolution Face Female Adolescents Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Goals Growth HIV HIV Infections HIV Seropositivity HIV envelope protein HIV-1 HIV/AIDS Health Image Immune Immune response Immunologic Markers Incidence Individual Infection Inflammatory Knowledge Limbic System Link Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Mediating Mental Health Methods Microglia Nature Neurocognitive Neurocognitive Deficit Neuroimmune Neurologic Deficit Outcome Outcome Measure Parents Participant Pathogenesis Pathway interactions Pattern Perinatal Peripheral Peripheral Blood Mononuclear Cell Peripheral Nervous System Phase Phenotype Population Prefrontal Cortex Research Research Infrastructure Respiratory physiology Rest Rewards Risk Role Shapes Social Change South Africa Spectrum Analysis Structure Time Tobacco Universities Viral Viral reservoir Virus Youth adolescent substance use age group antiretroviral therapy arterial spin labeling brain abnormalities cohort comparison group critical period emerging adult executive function experience fecal microbiome heart function high risk imaging facilities imaging modality in vivo inflammatory marker innovation insight morphometry multimodal neuroimaging myelination neurodevelopment perinatal HIV prospective resilience response spectrograph substance use synaptic pruning transmission process virus host interaction young adult

项目摘要

Project Summary Currently, over 30% of all new HIV infections globally are estimated to occur among youth ages 15 to 25 years. Adolescent girls are at very high risk of getting infected. This pattern is especially clear in sub-Saharan Africa, the region most severely affected by HIV/AIDS. Also, increasingly, children infected at birth grow into adolescents who have to deal with their HIV positive status. Combining the two, there are 5 million youth living with HIV(WHO). There is a global call to focus on the particular needs of youth. Youth living with HIV comprise two different sub-populations: those who are infected through sexual exposure (behaviourally infected yBHIV) and those infected through parent-to-child transmission (perinatally infected yPHIV), now surviving into young adults. 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. Substance use and HIV infection present further challenges to neurodevelopment and resilience in this vulnerable stage of development. Few studies have investigated substance use outcomes in yBHIV, or made direct comparisons by mode of infection. Studies which conflate yHIV by mode of infection may blur the substance use experiences of these two different sub-populations. The proposed study will elucidate mechanisms of substance induced neuroimmune dysfunction in youth living with HIV-1 (yHIV), who are on anti-retroviral therapy (ART), and will include youth between the ages of 15 and 21 yrs, including 200 yPHIV + 100 yBHIV + 100 healthy controls in Cape Town, South Africa. The proposed study will to follow an existing cohort of yHIV from Cape Town Adolescent Antiretroviral Cohort (CTAAC), into early adulthood in order to understand the individual and combined effects of substance use (SU) and HIV infection on brain structure and function, neurocognitive functioning and mental health. The long-term goal is to understand the drivers (structural/mental health/cognitive) of SU in youth living with HIV (yHIV) and the impact of SU on chronic HIV infection and general health including immune dysregulation, viral reservoir and other health outcomes measured in the CTAAC parent award, such as the stool microbiome, respiratory and cardiac function. 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 existing successful collaborations.

项目概要目前，全球所有新发艾滋病毒感染者中，估计有超过 30% 发生在 15 至 25 岁的青少年中。青春期女孩被感染的风险非常高。这种模式在撒哈拉以南非洲尤其明显，受艾滋病毒/艾滋病影响最严重的地区。此外，越来越多的儿童在出生时就被感染，长大后必须应对艾滋病毒呈阳性状况的青少年。两者加起来，有 500 万青年生活在患有艾滋病毒（世界卫生组织）。全球呼吁关注青年的特殊需求。感染艾滋病毒的青少年包括两个不同的亚人群：通过性接触而感染的人群（行为感染 yBHIV）以及那些通过亲子传播感染的人（围产期感染 yPHIV），现在存活到幼年成年人。青春期是大脑成熟的关键时期，髓鞘形成、皮质持续生长和突触修剪。边缘系统和前额皮质的逐渐和差异性成熟调节奖励和情感行为，以及执行控制。药物使用和艾滋病毒感染进一步显现在这个脆弱的发展阶段，神经发育和复原力面临挑战。很少有研究调查 yBHIV 的物质使用结果，或通过模式进行直接比较。感染。将 yHIV 与感染方式混为一谈的研究可能会模糊这些人的药物使用经历两个不同的亚人群。拟议的研究将阐明物质诱导的机制接受抗逆转录病毒治疗 (ART) 的 HIV-1 (yHIV) 青少年的神经免疫功能障碍包括年龄在 15 岁至 21 岁之间的青少年，其中包括 200 名 yPHIV + 100 yBHIV + 100 名健康对照者南非开普敦。拟议的研究将跟踪来自开普敦的现有 yHIV 人群青少年抗逆转录病毒队列（CTAAC），进入成年早期，以了解个人和物质使用（SU）和 HIV 感染对大脑结构和功能、神经认知的综合影响功能和心理健康。长期目标是了解驱动因素（结构/心理） SU 对艾滋病毒感染者 (yHIV) 青少年的健康/认知）以及 SU 对慢性 HIV 感染和一般健康状况，包括免疫失调、病毒库和其他健康结果 CTAAC 家长奖，例如粪便微生物组、呼吸和心脏功能。开普大学身体成像中心 (CUBIC) 拥有最先进的研究专用西门子 3 T Skyra MRI 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。我们已经开发出先进的能力脑形态测量、光谱学、扩散张量和功能成像。该项目建立在现有成功的合作。