BACKGROUND: Social determinants of health (SDH) include factors such as income, education, and race, that could significantly affect the human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS). Studies on the effects of SDH on HIV/AIDS are limited, and do not yet provide a systematic understanding of how the various SDH act on important indicators of HIV/AIDS progression. We aimed to evaluate the effects of SDH on AIDS morbidity and mortality. METHODS: A retrospective cohort of 28.3 million individuals was evaluated over a 9-year period (from 2007 to 2015). Multivariable Poisson regression, with a hierarchical approach, was used to estimate the effects of SDH-at the individual and familial level-on AIDS incidence, mortality, and case-fatality rates. FINDINGS: A total of 28,318,532 individuals, representing the low-income Brazilian population, were assessed, who had a mean age of 36.18 (SD: 16.96) years, 52.69% (14,920,049) were female, 57.52% (15,360,569) were pardos, 34.13% (9,113,222) were white/Asian, 7.77% (2,075,977) were black, and 0.58% (154,146) were indigenous. Specific socioeconomic, household, and geographic factors were significantly associated with AIDS-related outcomes. Less wealth was strongly associated with a higher AIDS incidence (rate ratios-RR: 1.55; 95% confidence interval-CI: 1.43-1.68) and mortality (RR: 1.99; 95% CI: 1.70-2.34). Lower educational attainment was also greatly associated with higher AIDS incidence (RR: 1.46; 95% CI: 1.26-1.68), mortality (RR: 2.76; 95% CI: 1.99-3.82) and case-fatality rates (RR: 2.30; 95% CI: 1.31-4.01). Being black was associated with a higher AIDS incidence (RR: 1.53; 95% CI: 1.45-1.61), mortality (RR: 1.69; 95% CI: 1.57-1.83) and case-fatality rates (RR: 1.16; 95% CI: 1.03-1.32). Overall, also considering the other SDH, individuals experiencing greater levels of socioeconomic deprivation were, by far, more likely to acquire AIDS, and to die from it. INTERPRETATION: In the population studied, SDH related to poverty and social vulnerability are strongly associated with a higher burden of HIV/AIDS, most notably less wealth, illiteracy, and being black. In the absence of relevant social protection policies, the current worldwide increase in poverty and inequalities-due to the consequences of the COVID-19 pandemic, and the effects of war in the Ukraine-could reverse progress made in the fight against HIV/AIDS in low- and middle-income countries (LMIC). FUNDING: National Institute of Allergy and Infectious Diseases (NAIDS), National Institutes of Health (NIH), US Grant Number: 1R01AI152938.