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

项目摘要 目前，全球所有新感染艾滋病毒的病例中，估计有30%以上发生在15至25岁的青年人中。 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感染， 必须处理艾滋病毒阳性状况的青少年。两者相加，有500万青年生活在 艾滋病毒（WHO）全球呼吁关注青年的特殊需要。感染艾滋病毒的青年包括 两个不同的亚群：通过性接触感染的人（行为感染的yBHIV） 和那些通过父母对子女的传播（围产期感染yPHIV），现在存活到年轻人， 成年人了青春期是大脑发育成熟的关键时期， 和突触修剪。边缘系统和前额叶皮质的逐渐和差异成熟调节 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呈现 在这个脆弱的发展阶段对神经发育和恢复力的挑战。 很少有研究调查yBHIV中物质使用的结果，或通过使用方式进行直接比较。 感染通过感染方式混淆yHIV的研究可能会模糊这些人的物质使用经历。 两个不同的亚群这项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HIV-1（yHIV）感染青年的神经免疫功能障碍， 包括15至21岁的青年，包括200名yPHIV + 100名yBHIV +100名健康对照， 南非，开普敦。拟议的研究将跟踪开普敦现有的yHIV队列 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感染对脑结构和功能、神经认知功能 功能和心理健康。长期目标是了解驱动因素（结构/心理 艾滋病毒感染青年（yHIV）的SU和SU对慢性艾滋病毒感染的影响， 一般健康状况，包括免疫失调、病毒储存库和其他健康结果， CTAAC家长奖，如粪便微生物组，呼吸和心脏功能。开普敦大学 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 优化了大脑成像，在撒哈拉以南非洲是独一无二的。我们已经开发出先进的 脑形态测量学、光谱学、扩散张量和功能成像。该项目建立在现有的 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.