People who inject drugs (PWID) face barriers to engagement in antiretro-viral treatment (ART) and medication-assisted treatment (MAT). We detail the design, rapid preparation and adaptation, and systematic implementation of a flexible, individually tailored intervention for PWID in multiple settings: Indonesia, Ukraine, and Vietnam. HPTN 074 integrated systems navigation and counseling to facilitate entry and adherence to ART and MAT. Site-level guidance on the intervention involved in-depth interviews (IDIs) among PWID and their supporters and site-specific document review. IDIs emphasized ART misinformation and importance of social support for adherence. The document review revealed differences in health care system barriers, requiring an intervention that was flexible and tailored enough to address key outcomes. Implementation included regular debriefs for iterative adaptations based on participants' needs, including booster counseling sessions and subsidizing pre-ART testing. HPTN 074 provides a unique framework implementing a flexible and scalable intervention to improve ART and MAT outcomes among PWID across multiple settings.