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

项目摘要 目前，据估计，全球所有新的艾滋病毒感染中有30%以上发生在15至25岁的青年中。 青春期女孩感染的风险很高。这种模式在撒哈拉以南非洲地区尤为明显， 受艾滋病毒/艾滋病影响最严重的地区。此外，出生时感染的儿童越来越多地成长为 不得不应对艾滋病毒阳性状态的青少年。两者加在一起，有500万青年生活在 感染艾滋病毒(世卫组织)。全球呼吁把重点放在青年的特殊需求上。感染艾滋病毒的青少年包括 两个不同的亚群：通过性接触感染的人(行为感染yBHIV) 通过亲子传播感染的人(围产期感染的yPHIV)，现在存活到年轻的 成年人。青春期是大脑成熟的关键时期，伴随着髓鞘形成和皮质生长。 以及突触修剪。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。物质使用和艾滋病毒感染进一步呈现 在这个脆弱的发展阶段，对神经发展和复原力的挑战。 很少有研究调查yBHIV的物质使用结果，或通过 感染。将yHIV按感染方式混为一谈的研究可能会模糊这些人的物质使用经验 两个不同的亚群。这项拟议的研究将阐明物质诱导的机制 正在接受抗逆转录病毒治疗(ART)的艾滋病毒感染者(YHIV)的神经免疫功能障碍 包括15至21岁的年轻人，包括200yPHIV+100yBHIV+100名健康对照 南非开普敦。这项拟议的研究将跟踪来自开普敦的现有yHIV人群 青春期抗逆转录病毒队列(CTAAC)，进入成年早期，以了解个体和 物质使用(SU)和HIV感染对脑结构和功能、神经认知的联合影响 功能和心理健康。长期目标是了解驱动因素(结构/心理 SU对青年HIV感染者的健康/认知)及SU对慢性HIV感染和 一般健康，包括免疫失调、病毒库和其他健康结果 CTAAC家长奖，如粪便微生物群、呼吸和心脏功能。开普敦大学 身体成像中心(CUBIC)拥有一台最先进的研究专用西门子3T Skyra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。我们已经开发了先进的 脑形态计量学、光谱学、扩散张量和功能成像。此项目建立在现有基础上 成功的合作。

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.