Reuben N. Robbins, Ph.D. - US grants

DESCRIPTION (provided by applicant): With 6.1 million HIV-infected individuals, South Africa is an LMIC with the world's largest population of people living with HIV. To address the resulting shortages in healthcare personnel, South Africa uses a task-shifting strategy in which lay health workers provide components of HIV care. Neurocognitive impairment (NCI) is one of the most common sequelae and comorbid conditions of HIV infection and has significant medical, functional, and public health consequences. NCI affects over half of HIV-infected individuals, yet often goes undetected in the clinical setting. Although - as in other chronic diseases - routine screening for NCI in HIV can enhance provider-patient communication to promote medication adherence and positive health outcomes, it faces numerous challenges, including the need for special equipment and highly trained personnel to administer, score and interpret screening tests. Mobile technology can offer a solution to this critical public health and medical care challenge by facilitating routine screening for NCI in HIV and other chronic illnesses. To this end, we developed NeuroScreen, a brief, easy-to-use NCI screening test app for Android devices, designed to be administered by a wide range of non- expert healthcare personnel in clinical settings. The app is standardized and highly automated, requires minimal training to administer, and does not require record-keeping or scoring. It can be used in clinic exam rooms, remote rural settings, and/or home visits and requires no paper forms, stopwatches, or other equipment. NeuroScreen results are available immediately and can be transmitted electronically to a variety of end-users, such as primary care providers, HIV or other specialists, and/or electronic medical records. The proposed study will (1) adapt NeuroScreen for administration by South African, Xhosa-speaking lay counselors; (2) evaluate the counselor-administered app's sensitivity and specificity to detect NCI among 100 HIV+ adults, as well as its usability and acceptability; and (3) explore the association between NeuroScreen results and medical health outcomes - i.e., objective behavioral and biological markers of ART treatment failure. These data will be the basis for future larger-scale research on implementation and scale-up of this mHealth tool for use in LMIC settings. NeuroScreen could be easily modified for use in other diseases and LMICs that rely on task-shifting due to limited healthcare resources. This project will build research capacity in South Africa in several ways. First, our in-country collaborators and partners in developing this proposal will continue to work with us in future research based on this study. Second, this study will build the South African software developers' capacity to apply their expertise to public health and clinical research. Third, we will offer in-service trainings on NCI and mHealth tools at DOH clinics and the University of Cape Town, as well as disseminate findings and lessons learned and conduct seminars on developing and implementing mHealth research studies and tools to UCT medical and research trainees.

South Africa (SA), a resource limited setting with the world?s largest population of people living with HIV, has hundreds of thousands of perinatally HIV-infected (PHIV+) youth who are rapidly becoming adolescents. PHIV+ adolescents must contend with the negative effects of life-long viral infection and chronic inflammation on their neurodevelopment, medical status, mental health, and, for many, the demands of lifelong ART adherence ? placing them at risk for not achieving these important milestones. Neurocognitive impairment (NCI) is chief among these negative effects. NCI in PHIV+ adolescents most commonly affects the neurocognitive domains of working memory, executive function and processing speed. NCI can affect youth?s ability to perform in and complete school, interact successfully with peers and adults, find employment, initiate and maintain long-term relationships, and function independently. NCI can also interfere with adherence to medication, which is critical in HIV, and increase poor decision-making and greater HIV transmission risk behaviors (e.g., unprotected sex). PHIV+ youth in SA are also at risk for NCI due to numerous psychosocial problems that are very common in resource limited settings, such as poverty and poor education. The first step in addressing NCI in PHIV+ adolescents is detecting and diagnosing it, but doing so in South Africa is seriously hampered. Few neurocognitive tests and screening tests exist for the hundreds of thousands of PHIV+ youth in SA. The tests that do exist for PHIV+ youth in SA require highly trained personnel to administer and score, take several hours to administer, lack ecological validity to predict real-world outcomes, and many suffer from cultural biases because they were developed for and normed on youth in the US or Europe. Given how overburdened the SA healthcare system is and its reliance on task-shifting various components of care to lay health workers (LHWs), without accurate, clinically useful, and relatively brief NC tests that can detect NCI and meet the demands of task-shifting in RLSs, PHIV+ adolescents in SA will not be assessed, missing opportunities to detect NCI and intervene. NeuroScreen is a brief, easy-to- use app for Android devices to assess and screen for NCI that is designed to be administered by a wide range of non- expert healthcare personnel in clinical settings. The app contains nine neurocognitive tests assessing processing speed, executive functions, working memory, verbal memory, and motor speed. It is standardized and highly automated, requires minimal training to administer, and does not require record- keeping or scoring. The proposed study will validate NeuroScreen for use with PHIV+ adolescents in SA by (1) evaluating its internal validity, (2) sensitivity and specificity to detect NCI compared to a gold standard neuropsychological test battery, and (3) characterize PHIV+ youth performance on it in the context of medical and psychosocial factors. The study will also generate preliminary normative performance data among 13-17 year adolescents in SA. A neurocognitive assessment tool like NeuroScreen could be easily modified for use in other disease populations and regions of the world that rely on task-shifting.

South Africa (SA), a resource limited setting with the world?s largest population of people living with HIV, has hundreds of thousands of perinatally HIV-infected (PHIV+) youth who are rapidly becoming adolescents. PHIV+ adolescents must contend with the negative effects of life-long viral infection and chronic inflammation on their neurodevelopment, medical status, mental health, and, for many, the demands of lifelong ART adherence ? placing them at risk for not achieving these important milestones. Neurocognitive impairment (NCI) is chief among these negative effects. NCI in PHIV+ adolescents most commonly affects the neurocognitive domains of working memory, executive function and processing speed. NCI can affect youth?s ability to perform in and complete school, interact successfully with peers and adults, find employment, initiate and maintain long-term relationships, and function independently. NCI can also interfere with adherence to medication, which is critical in HIV, and increase poor decision-making and greater HIV transmission risk behaviors (e.g., unprotected sex). PHIV+ youth in SA are also at risk for NCI due to numerous psychosocial problems that are very common in resource limited settings, such as poverty and poor education. The first step in addressing NCI in PHIV+ adolescents is detecting and diagnosing it, but doing so in South Africa is seriously hampered. Few neurocognitive tests and screening tests exist for the hundreds of thousands of PHIV+ youth in SA. The tests that do exist for PHIV+ youth in SA require highly trained personnel to administer and score, take several hours to administer, lack ecological validity to predict real-world outcomes, and many suffer from cultural biases because they were developed for and normed on youth in the US or Europe. Given how overburdened the SA healthcare system is and its reliance on task-shifting various components of care to lay health workers (LHWs), without accurate, clinically useful, and relatively brief NC tests that can detect NCI and meet the demands of task-shifting in RLSs, PHIV+ adolescents in SA will not be assessed, missing opportunities to detect NCI and intervene. NeuroScreen is a brief, easy-to- use app for Android devices to assess and screen for NCI that is designed to be administered by a wide range of non- expert healthcare personnel in clinical settings. The app contains nine neurocognitive tests assessing processing speed, executive functions, working memory, verbal memory, and motor speed. It is standardized and highly automated, requires minimal training to administer, and does not require record- keeping or scoring. The proposed study will validate NeuroScreen for use with PHIV+ adolescents in SA by (1) evaluating its internal validity, (2) sensitivity and specificity to detect NCI compared to a gold standard neuropsychological test battery, and (3) characterize PHIV+ youth performance on it in the context of medical and psychosocial factors. The study will also generate preliminary normative performance data among 13-17 year adolescents in SA. A neurocognitive assessment tool like NeuroScreen could be easily modified for use in other disease populations and regions of the world that rely on task-shifting.

There are 2.1 million children with HIV (CWH) under 15 years of age worldwide; the vast majority have perinatally-acquired HIV, reside in resource limited Low-and-Middle Income Countries (LMICs), and are surviving into adolescence and young adulthood. In Uganda, where the proposed study will take place, there are over 130,000 CWH under 15 years. CWH must contend with the negative effects of life-long viral infection and chronic inflammation on their neurodevelopment, medical status, mental health, and, for many, the demands of lifelong ART adherence ? placing them at risk for not achieving crucial developmental milestones. Neurocognitive impairment (NCI) is chief among these negative effects. NCI in CWH most commonly affects the neurocognitive domains of working memory, executive functions, and processing speed. NCI can affect children?s ability to perform in and complete school, interact successfully with peers and adults, initiate and maintain long-term relationships, and develop independence. NCI can also interfere with adherence to medication, which is critical in HIV, and increase poor decision-making and greater HIV transmission risk behaviors (e.g., unprotected sex) for older children and adolescents. The first step in addressing NCI in CWH is detecting it but doing so in Uganda faces numerous challenges. Few neurocognitive tests exist for Ugandan children 5-12 years of age. The tests that do exist require highly trained personnel to administer and score, take several hours to administer, and many suffer from cultural biases because they were developed for and normed on youth in the US or Europe. Without accurate, clinically useful, and relatively brief NCI assessments that can be administered accurately by all levels of staff, researchers and clinicians will remain severely limited in their capacity to assess CWH in Uganda, missing opportunities to study and detect NCI, as well as intervene. NeuroScreen is a brief, easy-to-use app for Android devices to assess for NCI that is designed to be administered by all levels of clinical staff. The app contains twelve neurocognitive tests assessing processing speed, executive functions, working memory, verbal memory, and motor speed. It is standardized and highly automated, requires minimal training to administer, and does not require record-keeping or scoring. It has been used successfully with adults and adolescents but has not been evaluated for use with children under 13 years. The proposed study will: (1) determine the necessary adaptations needed to make NeuroScreen usable, understandable, and acceptable to CWH under 13 years, and for HIV providers likely to administer it; (2) generate preliminary estimates of the adapted tests? validity indicators among CHW and matched controls 5-12 years of age; and (3) explore associations between NeuroScreen performance and behavioral health. These data will be the basis for future larger-scale research studies on NCI, as well as validation, implementation and scale-up of this mHealth tool for use in Uganda and other LMICs.