OBJECTIVE: To assess sex, age, regional differences, and the changing trend in human immunodeficiency virus and tuberculosis (HIV-TB) in different regions from 1990 to 2021, and project future trends. METHODS: Global Burden of Disease Study 2021 data were analyzed to assess HIV-TB incidence, death, prevalence, and DALY rates from 1990 to 2021, including different types of TB co-infections (drug-susceptible, multidrug-resistant, and extensively drug-resistant). Bayesian age-period-cohort models were used to forecast age-standardized DALY rates through 2035. RESULTS: In 2021, there were approximately 1.76 million HIV-TB infections and 200,895 deaths globally. The highest burden of HIV-DS-TB and HIV-MDR-TB was found in Southern Sub-Saharan Africa, while HIV-XDR-TB was most prevalent in Eastern Europe. The co-infection burden was highest among individuals aged 30-49. Key risk factors were unsafe sex, drug use, and intimate partner violence, with regional variations. The global burden of HIV-TB remains high, and age-standardized DALY rates are expected to increase in the coming years, especially in regions with low socio-demographic indices (SDI). CONCLUSION: The burden of HIV-TB co-infection correlates with the socio-demographic index (SDI): countries with a low SDI have a higher burden. Therefore, clinical diagnosis and treatment in such areas are more challenging and may warrant more attention. High death rates underscore the importance of early management.