Central Asia (CA) represents the most rapidly growing HIV epidemic region worldwide, concentrated in people who inject drugs (PWID) and their sexual partners. Scaling up opioid agonist therapies (OAT) in CA is the most cost-effective strategy to prevent new HIV infections, and more effective when combined with antiretroviral therapy (ART). CA countries have especially low OAT (and ART) coverage and are uniquely impacted by their proximity to opioid trade routes, a myriad of patient, provider, healthcare and policy barriers and suboptimal implementation. CA countries share a similar rigid Semashko healthcare system, which can be especially challenging for implementing evidence-based practices (EBPs). Moreover, the HIV treatment cascade differs in the three countries of Kazakhstan (KZ), Kyrgyzstan (KY) and Tajikistan (TJ), generally with low levels of case detection, ART prescription and viral suppression. They also differ by OAT coverage, with all being suboptimal and well-below international targets for the 120,500, 25,000 and 22,500 PWID, respectively. We propose to use the Network for the Improvement of Addiction Treatment (NIATx) implementation strategy to scale-up OAT in three diverse CA countries guided by the EPIS (Exploration-Planning-Implementation- Sustainment) framework. Using our experiences with NIATx to scale-up OAT, we will use the EPIS framework where we will first assess the barriers and facilitators to OAT scale-up, including the inner and outer contexts as well as bridging factors. These findings will guide preparation and implementation efforts using NIATx. Collaborative learning is key feature of NIATx that can be used in diverse contexts and is an iterative process that promotes change. Understanding the trajectories of implementation, a core feature of EPIS, may in this context emerge through creating communities of practice, especially when cohesion and/or competence evolves through this process, and may guide other healthcare delivery challenges in the region (e.g., HIV, TB). Using NIATx to build important regional expertise and competence and understanding implementation trajectories in this context should help support OAT program sustainability. As part of our implementation and sustainability plan, and consistent with NIATx, we will convene stakeholder meetings to bridge inner and outer factors to guide initial and ongoing implementation, review findings from our studies and use information to inform policies for expanding OAT in each CA country. These meeting will inform implementation and guide policy changes to promote sustainability. Significance is justified by the regional needs to prevent HIV in PWID and their sexual partners and the lack of scale-up of EBPs. Innovation is enhanced not only by using NIATx in a new context, but by more comprehensively understanding scale-up trajectories in this context. Success is likely to be high given the experience of the US and Central Asian teams, their previous collaborativ...