Project Summary Breast cancer is the leading cause of cancer mortality among women globally with over 626,000 deaths reported in 2018. Despite substantial reductions in breast cancer mortality in developed countries, low- and middle- income countries (LMICs) continue to experience a high fatality rate. The disparity is more pronounced in Sub Saharan Africa (SSA) and in HIV prevalent regions, where HIV-infected (HIV+) breast cancer patients have a significantly increased risk of all-cause mortality. The “World Health Organization-Choosing Interventions that are Cost-Effective” team assessed systemic treatment for breast cancer at 95% coverage in SSA as cost-effective. Subsequently robust evidence-based resource-stratified guidelines have been developed to promote high quality breast cancer therapy delivery in SSA. However critical real-world data are lacking on the treatment fidelity and the implementation of guideline-based care. These data are critical to understanding whether inferior outcomes are related to the quality or extent of guideline implementation or other unrelated factors. If interventions that maximize treatment fidelity and minimize random variability are implemented, targeted outcomes will likely be achieved. The long-term goal is to improve survival outcomes in HIV+ and HIV- breast cancer patients in SSA by designing targeted interventions to increase high-quality therapy delivery. The objectives of this application are to allow Dr. Martei to formally train to become an independent investigator in implementation science in cancer care delivery in SSA, and to obtain practical skills through the following research aims: 1) compare treatment fidelity between HIV+ and HIV- breast cancer patients receiving curative intent therapy and identify HIV modifiers of fidelity; 2) using mixed methods design and a deviance sample of patients with high and low fidelity identify socioeconomic and cultural modifiers of fidelity; and 3) using the collaborative intervention planning framework to identify targets for guideline adaptation and develop a menu of implementation strategies and intervention trials to promote treatment fidelity. This study in Botswana builds upon 15 years of collaborative research between Botswana and the University of Pennsylvania, including a multidisciplinary group of US- and Botswana-based senior mentors, and the strong publicly-funded healthcare system for HIV and breast cancer. This is aligned with the National Cancer Institute Center for Global health priority areas of “Strengthening Global Cancer Research and Resource-Appropriate Cancer Control Strategies” to promote cancer research and control efforts that are evidence-based and sustainable in LMICs.