Background: HIV/AIDS remains one of the most significant global public health issues. The COVID-19 Pandemics put unprecedented pressure on healthcare systems. Thus, our objective was to assess the burden and progress in controlling HIV/AIDS from 1990 to 2021 and to evaluate the potential impact of the COVID-19 pandemic. Methods: Using data from the Global Burden of Disease Study 2021, we analyzes global, regional, and national trends in HIV/AIDS, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021.In addition, the burden of disease was analyzed for different age groups, sexes, and socio-demographic indices (SDIs).We used estimated annual percentage change (EAPC) to quantify time trends and calculated percent changes in deaths, incidence, incidence-mortality ratio (IMR), and incidence-prevalence ratio (IPR) to assess control progress. Findings: The global age-standardized incidence rate (ASIR) of HIV/AIDS has decreased from 36.54 per 100,000 population in 1990 to 20.77 per 100,000 population in 2021. However, the global age-standardized prevalence rate (ASPR) has increased from 149.23 per 100,000 in 1990 to 483.14 per 100,000 in 2021. Sub-Saharan Africa has experienced a marked decline in prevalence, but still has the highest global prevalence. During the COVID-19 pandemic, global trends in HIV/AIDS showed an accelerated decline in morbidity and mortality, with slowdowns or reversals in prevalence growth in most regions. Between 2020 and 2021, the global decline in HIV incidence accelerated from an EAPC of –2.49% to –5.25%. By 2021, HIV/AIDS incidence rates had shifted to be higher among males than females, with prevalence, mortality, and disability-adjusted life years (DALYs) increasingly affecting males over 30. Age-specific analyses revealed that infants had the highest incidence rates in 2021, while individuals aged 30–49 bore the highest prevalence and mortality burdens. Between 2010 and 2021, HIV-related deaths decreased by 39.70%, but this does not meet the 75% reduction target set for 2020. Result: HIV/AIDS remains a global public health challenge, especially in sub-Saharan Africa. Global HIV incidence declined from 1990 to 2019, but the disruption caused by the COVID-19 pandemic from 2020 to 2021 poses new challenges. Continued and targeted efforts are necessary to reduce the disease burden and work towards global HIV/AIDS control and prevention goals.