Background <p>Inequality is a consistent issue throughout the process of HIV/AIDS prevention and control. There is currently a lack of quantitative research on cross-country inequalities in HIV/AIDS.</p> Methods <p>This study quantified the burden and inequalities of HIV/AIDS across 204 countries using GBD 2021 data. Age-standardized rates (ASRs) and uncertainty intervals (UIs) were used to quantify the burden of HIV/AIDS. Estimated annual percentage changes (EAPCs) of ASRs with 95% confidence intervals (CIs) were calculated to assess trends. The Slope Index of Inequality (SII) and Concentration Index (CI) were employed to quantify the degree of inequality in countries or regions with different Sociodemographic Index (SDI) levels.</p> Findings <p>In 2021, the ASRs of incidence(ASIR), prevalence(ASPR), mortality(ASMR) and Disability-Adjusted Life Years (DALYs)(ASDR) of HIV/AIDS per 100,000 people were 20.77 (95% UI: 18.77-23.02), 483.14 (95% UI: 459.02-511.43), 8.71 (95% UI: 8.10-9.56) and 496.39(95% UI: 456.10-554.21) globally. In 204 countries or regions, Lesotho with the highest prevalence in 2021 is 22,564.56 times the lowest in Albania. In terms of changes in ASIR, ASPR, ASMR and ASDR, there were 100 countries, 171 countries, 102 countries and 101 countries showed upward trends, respectively. According to the cross-country social inequalities analysis, the SII changed from -291.78 to -67.24 for ASIR, from -1117.87 to-2312.47 for ASPR, from -42.48 to -49.32 for ASMR and from -2354.77 to -2557.03 for ASDR. The concentration index values ranged from 0.3 to 0.6.</p> Conclusions <p>Countries or regions with lower socio-demographic development disproportionately bear a heavier burden of HIV/AIDS, and these disparities are widening over time between the lowest and highest socioeconomic status groups. Additionally, the rising trend of HIV/AIDS burden in populations with high and middle SDI levels is alarming.</p>