PROJECT SUMMARY Adolescents living with HIV (ALHIV) have been shown to experience neurocognitive impairment compared to their uninfected peers, but the underlying neurophysiology considered to be the fundamental building blocks of complex cognitive processing have not been rigorously studied within this population. Therefore, there is a crit- ical need for a comprehensive study of neurophysiology and cognitive function in ALHIV, especially in sub-Sa- haran Africa, which comes with unique health and socio-demographic risk factors that compound the adverse effects of HIV infection. The specific objectives of the proposed project is to: (1) determine the impact of HIV infection on neurophysiology and neurocognition in perinatally-infected adolescents and identify potential me- diating factors; and (2) build capacity for interdisciplinary neurophysiological research in sub-Saharan Africa by supporting intensive training for faculty development and tiered mentoring in neurophysiological methodologi- cal techniques. The central hypothesis is that ALHIV will show altered neurophysiology and impaired cognition compared to their unexposed peers. The rationale for this study is that evaluations utilizing event-related poten- tials (ERP) are uniquely suited determine which sensory and information processing stages are impaired and contribute to cognitive abnormalities in ALHIV. In Aim 1, we will determine the impact of HIV infection on neurophysiology and neurocognition in perinatally-infected adolescents and identify potential mediating socio- demographic and health/medical factors. To achieve this aim we will characterize ERP responses and their rela- tionship to cognitive function in ALHIV (14-17 years old) compared to uninfected adolescents (n=50/group) to develop a model to determine childhood factors predictive of poor neurophysiological and cognitive outcomes. Cognitive and sensory ERP paradigms, associative motor learning and motor coordination tasks, and a culturally adapted version of the NIH Toolbox Fluid Cognition tests will be administered within Aim 1. In Aim 2, we will build capacity for interdisciplinary neurophysiological research by supporting intensive training for faculty de- velopment and tiered mentoring in neurophysiological methodological techniques. Within this aim, we will sup- port the faculty and students within the Moi University’s training programs in performing neuropsychological work, for both clinical and research purposes. This will be done through a series of training workshops, monthly virtual seminars, and on-site supervision, which will culminate within a national symposium to foster neuro- physiological research collaboration across Kenya. The proposed work is significant because it will be the first comprehensive neurophysiological study of ALHIV in sub-Saharan Africa, and Moi University will be the only Kenyan academic center with sustainable capacity for research in neurophysiology. Funding this proposal would strengthen and promote national collaboration aimed at identifying mediating health and sociodemographic fac- tors for intervention and facilitating the identification of therapeutic targets to improve the outcomes of individ- uals across the African continent.

PROJECT NARRATIVE Adolescents living with HIV have been shown to experience neurocognitive impairment compared to their uninfected peers, but the underlying neurophysiology considered to be the fundamental building blocks of complex cognitive processing have not been rigorously studied within this population. The proposed research will explore the interaction between HIV and neurophysiology to (1) determine the potential neurophysiological impact of perinatally acquired HIV in adolescents and its relationship to cognitive deficits using a comprehensive battery of neurophysiological tasks and cognitive measures; and (2) support capacity building for interdisciplinary neurophysiological research in Kenya. Thus, the proposed research is relevant to the NIH’s mission, as it develops fundamental knowledge to enhance health and reduce the burdens of human disability.