STATEMENT The International Research Scientist Development Award affords an ideal mentorship opportunity to support the transition to independence of the candidate, an internist, pediatrician and pediatric infectious diseases physician with expertise caring for children and adults with HIV and tuberculosis (TB). The candidate?s long-term goal is to become an independent investigator, generating much needed evidence to inform child HIV and TB policy and practice. The candidate is based full-time in Eswatini and will work across the Baylor International Pediatric AIDS Initiative (BIPAI) network of clinics in Eswatini, Lesotho, Botswana, Malawi, Tanzania and Uganda to implement this multinational research study and accomplish the stated aims. The proposed research will guide implementation of differentiated service delivery for children and adolescents living with HIV (CALHIV) at both high and low risk of adverse HIV and HIV associated TB outcomes.
Aim 1 will derive and validate a mortality clinical prediction tool for CALHIV to predict the risk of death 12 months after the initiation of antiretroviral therapy. This tool will be derived and validated using retrospective data from across the BIPAI network.
Aim 2 of the proposal will develop a clinical prediction tool for viral non-suppression 12 months from study enrollment using prospectively collected clinical data and considering additional psychosocial variables, describing the myriad of factors impacting antiretroviral therapy adherence.
Aim 3 will also harness the strength of the BIPAI network to retrospectively determine TB incidence and mortality rates in CALHIV associated with the different isoniazid preventive therapy (IPT) strategies implemented according to evolving national guidelines across the BIPAI network. This data is urgently needed to i) inform evidence-based implementation of IPT in children receiving antiretroviral therapy, and ii) design prospective studies of new shorter-course tuberculosis preventive therapy regimens. Complementing the described research, the candidate will take courses in data science, data management, epidemiology, and clinical informatics, culminating in a master?s degree in epidemiology. Further, the candidate will benefit from direct supervision and guidance from a strong mentorship team that will be led by Dr. Mandalakas and Dr. Chiao (co-primary mentors). Dr. Mandalakas has over two decades of experience mentoring young physician scientists in global child health research and Dr. Chiao is an internationally recognized expert in the epidemiology of HIV associated malignancies. Dr. Lukhele (LMIC mentor and Executive Director at the Baylor Children?s Foundation-Eswatini) has extensive experience implementing public health research in Eswatini. Dr. Kirchner (co-mentor) will supervise the statistical analysis employed in this proposal, Dr. Skinner (co-mentor) will guide qualitative methods, and Dr. Maldonado (co-mentor) will provide technical expertise gathered from a career devoted to pediatric HIV epidemiology.
A public health approach to the management of children and adolescents living with HIV in sub-Saharan Africa has increased access to care but there remains a need for differentiated service delivery with intensified treatment and supportive strategies for children at higher risk of adverse outcomes. The clinical predication tools developed in this study will identify children at risk a-priori and avert unnecessary morbidity and mortality. This proposal will also define risk factors for TB disease in children living with HIV, identify those most likely to benefit from TB preventive therapy, and estimate the risk reduction associated with three different preventive therapy approaches; this knowledge will guide the design of prospective studies to investigate shorter tuberculosis preventive therapy regimens and inform evidence based TB preventive therapy strategies.