Project Summary/Abstract – Infectious Disease Epidemiology and Social-Behavioral Theory Core The overarching goal of the Infectious Disease Epidemiology and Social-Behavioral Theory Core (IDEST) is to support and train CDUHR investigators to apply theories and knowledge about multilevel factors, including current large-scale trends and events that are affecting HIV transmission, natural history, prevention, and clinical care, so that they are prepared to develop and carry out rigorous high-impact research that will contribute to ending HIV among people who use drugs (PWUD). (We refer to these large-scale disruptive trends and events as Big Events and Big Trends (BE/BT).) There has been a recent resurgence in new HIV infections and outbreaks among PWUD in the US and abroad, and, in many settings, the COVID-19 pandemic has generated the same circumstances that led to those outbreaks. This signals the need for a reinvigorated HIV research agenda. The IDEST Core has the following Specific Aims: 1) Encourage and support CDUHR investigators in applying and integrating knowledge and theory about substance use and HIV epidemiology, prevention, and treatment to enhance current studies and to develop and conduct new clinical, social-behavioral, and epidemiologic research that will contribute to ending HIV in PWUD; 2) Provide training on multilevel factors that may promote or impede ending HIV in the context of societal disruption, leading to studies that take these factors into account; and 3) Lead the field in guiding a broad research and training agenda by developing and disseminating relevant existing and new transdisciplinary theories and frameworks, with a focus on multilevel and time-varying considerations generally and BE/BT in particular. Core members are experts in the epidemiology, prevention, care and treatment of HIV infection and HIV- related related co-morbidities, co-infections, and complications; in the study of substance use including substance use disorders, and harm reduction; and in the development and use of relevant theories and novel, theory-based metrics. All Core members have been highly productive in the field and within the Center. The Core will provide training and consultation, and will take the lead within the Center on bringing emerging, scientifically relevant issues, new theories, and advances in epidemiologic, biomedical and clinical aspects of HIV and substance use to CDUHR investigators, with a focus on new and early stage investigators (new/ESI) and underrepresented investigators. The IDEST Core will collaborate with other Cores and Center Leadership to support CDUHR investigators to develop innovative high impact studies which will lead to new knowledge related to the multilevel factors driving HIV among PWUD to guide interventions and policies promoting progress toward eliminating HIV.