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The Institute of Medicine (IOM) recommends the use of HIV prevention interventions with proven efficacy to avert new infections. Given the time and cost associated with the development, implementation and evaluation of efficacious HIV interventions, adapting existing evidence-based interventions (EBIs) to be appropriate for a myriad of at-risk populations may facilitate the efficient development of new EBIs. Unfortunately, few models of theoretic frameworks exist to guide the adaptation of EBIs. Over the past few years, the authors have systematically developed a framework for adapting HIV-related EBIs, known as the “ADAPT-ITT” model. The ADAPT-ITT model consists of 8 sequential phases that inform HIV prevention providers and researchers of a prescriptive method for adapting EBIs. The current article summarizes key components of the ADAPT-ITT model and illustrates the use of the model in several case studies.