Project Summary / Abstract The primary purpose of this K24 renewal proposal is to support mentorship by Dr. Lockman of early career investigators from the US and Africa in conducting global patient-oriented research. This next generation of investigators will need to tackle ongoing global infectious disease epidemics (such HIV, COVID-19, tuberculosis, malaria, and antimicrobial resistance) and to respond rapidly to future emerging pandemics and pathogens. Effective mentorship of early career investigators to conduct clinical research in resource- constrained settings requires substantial time and effort by experienced mentors, and the need for such mentors exceeds their availability. The initial K24 project period permitted Dr. Lockman to successfully mentor more than 20 early career investigators (half of them from Africa) to lead clinical research projects, many of whom were able to quickly respond to the severe COVID-19 epidemic in Botswana because of prior training. This K24 grant also allowed Dr. Lockman to gain additional skills in designing and conducting patient-oriented research in resource-constrained settings with a focus on HIV (particularly in pregnancy) and COVID-19. Currently, nearly one in five adults in many sub-Saharan African countries is living with HIV; the impact of HIV co-infection on COVID-19 clinical outcomes and on SARS-CoV-2 viral evolution in settings with both very high HIV prevalence and high COVID incidence are unknown. In addition, the impact of widely used HIV antiretroviral treatment (ART) regimens during pregnancy on birth outcomes and on long-term maternal and child health and development are not well understood. The research aims of this project, which Dr. Lockman will mentor early career investigators from Africa and the US to lead, include studies of the role of HIV co- infection in several aspects of SARS-CoV-2 infection in Botswana -- specifically, the impact of HIV infection on long COVID and on the emergence of SARS-CoV-2 mutations/variants, by SARS-CoV-2 vaccination status. Additional mentored aims will evaluate the impact of different ART regimens during pregnancy on cardiometabolic factors in women (specifically, pregnancy and postpartum weight gain, and markers of diabetes and metabolic syndrome in pregnancy), and the association between these cardiometabolic factors and pregnancy outcomes and child health/growth. Dr. Lockman’s mentees will use existing data and samples for these aims, including from studies that she leads (multi-country IMPAACT 2010/VESTED randomized trial of 3 ART regimens in pregnancy and a new R01-funded study of child developmental/behavioral outcomes after in utero exposure to different maternal ART regimens in Botswana) and from stored clinical SARS-CoV-2 samples and related electronic routine health databases in Botswana. Dr. Lockman will also help her mentees access a wealth of other existing data, resources, and co-mentors. The overarching goal of this K24 renewal proposal ...