The Health Resources and Services Administration Special Projects of National Significance launched the Systems Linkage and Access to Care for Populations at High Risk of HIV Infection Initiative in 2011. Six state departments of health were funded to utilize a modified Learning Collaborative model to develop and/or adapt HIV testing, linkage to care and retention in care system-level interventions. More than 60 Learning Sessions were held over the course of the Learning Collaborative. A total of 22 unique interventions were tested with 18 interventions selected and scaled up. All interventions were created to impact services at a systems level, with standardized protocols developed to ensure fidelity. Our findings provide key lessons and present considerations for replication for use of a modified Learning Collaborative to achieve state-level systems change.