The renewal of the University of California San Francisco (UCSF)/Vitalant Research Institute (VRI), University of Cape Town (UCT) and South Africa National Blood Service (SANBS) Blood Research and EnhAnced Training against HIV in South Africa (BREATH-SA) program will train hematologists and blood bankers to perform high-quality HIV research to address relevant research questions in South Africa. South Africa needs ongoing research on its HIV epidemic’s impact on HIV-related hematologic diseases and the national blood supply. This proposal builds upon a 22-year history of HIV research collaboration between SANBS and UCSF/VRI and a 10-year research partnership with UCT under the NHLBI-funded REDS-III International HIV research network. The first five years of our program have made substantial progress towards our previous specific aims of building research capacity at SANBS and UCT, offering numerous training activities, graduating 13 Master’s and PhD students and achieving a robust publications record. However, our updated needs assessment has indicated that better career support, increased mentoring and more outreach to historically disadvantaged institutions is needed to achieve our overarching goal of creating sustainable centers of excellence in HIV-related transfusion medicine and hematology research enterprise in South Africa. For this renewal, we propose these Specific Aims: 1) Train the next generation of clinical researchers in HIV hematology and transfusion medicine to become independent researchers who will address emerging health challenges in these areas; 2) Strengthen institutional research capacity in applied HIV research at the SANBS Research and Development Academy and clinical and translational HIV research at the UCT Haematology Division; and 3) Develop a South African center of excellence in HIV hematology and transfusion medicine that will reach out to historically disadvantaged institutions and address inequities in research opportunity. We plan a four-tiered educational approach for trainees at various levels: in-country short courses on clinical research methodology, protocol design and manuscript preparation will reach a large number of trainees; for a smaller number lacking skills in study design, biostatistics and data analysis we propose medium-term course work in Cape Town and San Francisco; for the most promising, Master’s and PhD degree enrollment at the UCT School of Health Sciences; and for graduates of the program, a new early-stage investigator tier providing career mentorship and grantsmanship training. All trainees will be mentored as they accomplish research projects, compete for mini- grants funded by the program and publish manuscripts. Research resources include the HIV lymphoma registry and clinical resources at UCT, archived data and specimens from the REDS-III HIV research network and real- time HIV testing data from blood centers. High impact research topics include: HIV lymphoma biology, clinical cours...