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

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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.