Project Summary TB and HIV are Top 10 causes of child mortality in sub-Saharan Africa. Short-course combination TB preventive therapy (TPT) and PMTCT are highly effective and hold promise to reduce the 120,000 new HIV diagnoses and the 102,000 child TB deaths, of which most occurred in HIV-infected or HIV exposed and uninfected (HEU) children. TPT and PMTCT effectiveness require improved access to pediatric preventive care. In South Africa, nearly two thirds of TB-exposed children are also HIV-exposed. Integrating these prevention services into one community-based intervention could improve access to care, shorten time to diagnosis and treatment of TB and HIV, and ultimately reduce TB and HIV associated child mortality. Prior studies have shown community health workers can successfully screen and treat young children for pneumonia, malaria and neonatal sepsis. Their effectiveness in conducting community-based pediatric TB/HIV prevention services is unknown. During this K23 Award, we propose the following research aims: 1) use stakeholder input to adapt a community-based, pediatric TB/HIV prevention intervention and design an associated implementation strategy, 2) determine the accuracy of TB/HIV preventive care provided by a community health worker, and 3) determine whether community-based versus clinic-based contact tracing increases the identification of at-risk children under 5 years old. This research will be nested in a UNITAID project that aims to catalyze uptake of “3HP,” a new TPT regimen consisting of weekly rifapentine/isoniazid for people living with HIV and TB-exposed children. To date, I have acquired skills in the design, conduct and analysis of clinical trials. I will compliment this training with advanced coursework and practical experience in 1) qualitative study design, data collection and analysis, 2) the application of implementation science frameworks to analyze context, optimize interventions and evaluate implementation processes, and 3) the design and analysis of health services research. Together, this skill set will allow me to conduct hybrid effectiveness- implementation clinical trials in TB and HIV prevention that will allow for improved understanding of an intervention's effectiveness to inform sustainability and transferability to other settings. These research and career development plans will be accomplished under the guidance of an international team of mentors with expertise in TB and HIV, implementation science, qualitative research, pediatrics and health services research. The data collected and skills earned through this K23 Award will lead to an R01 application that will rigorously test the community-based intervention and implementation strategy's effectiveness in improving clinical TB and HIV prevention outcomes. Over the next four years, through the proposed mentorship, coursework and research, I will develop the expertise necessary to become an independent clinician scientist and expert in the field of pe...