Project Summary/Abstract – Transdisciplinary Research Methods Core The overarching goals of the Transdisciplinary Research Methods (TRM) Core are to (1) train and support our affiliated investigators in application of relevant research methods, including methods that may be new or complex, (2) make our investigators aware of innovative, cutting-edge methods that may be useful in their work and can open up possibilities that inspire new research questions, and (3) contribute to methodological advances. One primary area of emphasis will be on methods needed to understand the impacts of multilevel, time-varying processes and Big Events/BigTrends (BE/BT) on HIV prevention and care among PWUD. To support the work of a multidisciplinary set of investigators, we represent a range of expertise that includes field research and sampling; ethnography; infectious disease etiology, epidemiology and surveillance; community- engaged research; intervention design and testing, including optimization; and (now) designs and methods for causal inference, and the frameworks and methods of implementation science. This expertise is needed to understand how BE/BT impact the lives and health of PWUD, and to carry out research to develop interventions that will be relevant, resilient, and adaptable to societal changes. Building on prior successes, this Core will continue to focus on assisting affiliated investigators to integrate study design and methods with theories of prevention and care; create testable models of causal pathways; detect and respond to HIV outbreaks and other sequelae of BE/BT; and develop, test and implement potent and sustainable social, behavioral, and social-structural interventions. Specific Aims of the TRM core are: Aim 1. Lead the field and support CDUHR affiliated investigators in applying methods to enhance research conducted in the context of disruptions due to BE/BT by providing training, seminars, and consultation on quantitative, qualitative, and mixed methods, including the creative application and novel extensions of existing methods. Aim 2. Lead the field in the integration of the multiphase optimization strategy (MOST), implementation science (IS), and community-based participatory research (CBPR) methods, and build the capacity of CDUHR investigators to develop highly effective, efficient, implementable, and sustainable behavioral, biobehavioral, and social- structural interventions for prevention and treatment of HIV among PWUD by providing training and support in this area. Aim 3. Disseminate new research methods to the larger field, particularly methods relevant to responding to societal changes which may undermine or facilitate effective HIV prevention and care among PWUD.