BackgroundHigh HIV prevalence has been documented among people who use drugs (PWUD) in Myanmar particularly in mining and borderland areas. We estimated incidence of HIV among PWUD (via injecting and other routes) and examine associations between location in mining or borderland areas, migration and risk of infection.Methods and findingsAnalysis of data among PWUD registered at harm reduction programmes across Sagaing region, Kachin, and Northern Shan States between 2014-2021. Data on sociodemographic, drug use characteristics and clinic-level data on borderland or mining locations were collected at time of registration. Characteristics, repeat HIV testing and HIV seroconversion were analysed using a cohort approach and Poisson regression models examining associations between location in a borderland or mining area, migration and incidence of HIV, adjusting for confounders. Data were available from 85093 clients, 52526 reported HIV tests and 20.0% were seropositive. 38670 clients had no or only one recorded HIV result. The median time between HIV tests was 1.1 years. Among 13,359 clients with 2 or more HIV tests the HIV seroconversion rate was 3.8 per 100 person years (pyrs) (95% CI 3.6-4.0). Incidence among those who injected drugs was 6.9 per 100/pyrs, 8.9 among those aged ≤ 25 years, 2.3 among women, 2.3 among those who had migrated, 5.6 among those located in border areas, and 3.7 among those in mining areas. After adjusting for confounders HIV incidence remained higher for people located in borderland areas (Incidence Rate Ratio 1.67 95% CI 1.13-2.45) and lower among those who had migrated (IRR 0.56, 95% CI (0.39-0.82). There was no evidence of association between location in a mining area and HIV seroconversion.ConclusionsFindings highlight the need to intensify harm reduction interventions with a focus on cross-border interventions. Increasing uptake of HIV testing alongside the scale up of evidenced based interventions to address sexual and injecting risk practices including PrEP, distribution of condoms, needles/syringe distribution and opioid agonist therapies is urgently needed to curb the high rates of HIV transmission among PWUD particularly among young people.Author summaryWhy was this study done?Increased availability of drugs in producer countries or along trafficking routes alongside political instability and reduced enforcement has been linked to elevated drug use and outbreaks of HIV infection.Few studies focus on the extent to which structural factors, that is, political, social, or physical aspects of the environment, are associated with HIV infection in Myanmar though elevated HIV prevalence has been observed in rural and borderland areas.This study contributes to the limited evidence base on HIV incidence in South East Asia and Myanmar specifically.What did the researchers do and find?This study measures HIV incidence among people who use drugs using routine programmatic data and provides estimates of differential HIV risk associated with location in borderland and mining areas and experience of migration.We estimate HIV incidence to be 3.8 per 100 person years among people who use drugs, with higher incidence among those who inject and younger ages (<25 years)We identify people who use drugs registered at services in borderland areas to be at elevated risk of HIV acquisition and migrants at decreased risk.What do the findings mean?Findings point to the imperative for expanding HIV prevention interventions among PWUD, with a focus on cross-border interventions and addressing injecting and sexual risk practices.Findings support the emerging body of evidence highlighting the utility of programmatic data to estimate HIV incidence among key populations.Understanding differential risk in infections among people who use drugs and structural determinants is key to creating enabling environments through which effective HIV treatment and prevention interventions can be delivered.