Background:Although HIV infection in the Russian Federation was historically concentrated among marginalized populations (people who inject drugs, sex workers, MSM, and the prison population), recent evidence suggests that it has become a more generalized epidemic. The objective of our research was to explore how these trends in HIV prevalence and HIV-related mortality compare across Russia.Methods:We calculated HIV-associated mortality for both male and female individuals in each region (oblast) of the Russian Federation using data from the Russian Fertility and Mortality Database (RusFMD). Using current data on HIV prevalence, we computed the correlation between HIV prevalence and HIV-associated mortality. We also used oblast-level data to examine the associations between HIV prevalence and the risk factors most commonly associated with HIV infection.Results:Over the past 20 years, the Russian Federation has experienced a rapid increase in HIV-associated mortality in both male and female individuals. Our findings revealed significant heterogeneity, with higher rates of HIV-associated mortality reported in oblasts in the Siberian and Ural Federal Districts. There is a strong correlation (0.8) between HIV-associated mortality and virus prevalence. These findings confirm that there are regional disparities in access and adherence to antiretroviral therapy (ART), as indicated by the low correlation (−0.4) between virus prevalence and access to ART coverage. The results from our modeling analysis revealed that, in addition to the factors most commonly associated with this disease (e.g. intravenous drug use), knowledge about sexual transmission of HIV in the general population has a broad impact on its prevalence at the oblast level.Conclusion:Interventions that reduce HIV prevalence, for example, opioid substitution therapy and needle-sharing programs for people who inject drugs, as well as the increased availability of educational and preventive programs may halt the spread of HIV across the Russian Federation. Similarly, increased access to treatment could help in reducing HIV-related mortality.