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Background: Human immunodeficiency virus (HIV) infection is a health problem in Brazil and worldwide. Without treatment, the infection can progress to Acquired Immunodeficiency Syndrome (AIDS), with a high mortality potential. The objective of this study was to analyze the time trend of AIDS mortality in Brazil, macro-regions, federal units and their respective capitals, from 2012 to 2022. Methods: This is a time-series study of all AIDS deaths in Brazil from 2012 to 2022. The study included the annual number of deaths and the crude and standardized mortality rates. The Joinpoint regression model was used for the time analysis of the standardized rates. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated. A 95% confidence interval (CI) and a 5% significance level were used. Results: During the period analyzed, 128,678 AIDS deaths were recorded in Brazil, with a crude mortality rate of 6.3/100,000 and a standardized mortality rate of 5.3/100,000. From 2012 to 2020, three regions showed a declining trend in AIDS mortality: Central-West (AAPC − 2.3%; 95%CI -4.3 to -0.21; p = 0.03), Southeast (AAPC − 5.6%; 95%CI -6.8 to -4.0; p < 0.001), and South (AAPC − 4.4%; 95%CI -5.27 to -3.6; p < 0.001). There was also a downward trend in 10 states and 10 capitals. There was an increase in the number of deaths from 2020 onwards in the North, Northeast and Southeast regions compared to 2019. Conclusion: There was a downward trend in AIDS mortality from 2012 to 2020 and an upward trend from 2020 to 2022. The regional differences observed could reflect the social disparities that exist in Brazil. In addition, the Covid-19 pandemic has had an impact on the process of dealing with HIV in Brazil. [ABSTRACT FROM AUTHOR]