BACKGROUND: Despite the great progress made over the last decades, stronger structural interventions are needed to end the HIV/AIDS pandemic in Low and Middle-Income Countries (LMIC). Brazil is one of the largest and data-richest LMIC, with rapidly changing socioeconomic characteristics and an important HIV/AIDS burden. Over the last two decades Brazil has also implemented the world's largest Conditional Cash Transfer programs, the Bolsa Familia Program (BFP), and one of the most consolidated Primary Health Care (PHC) interventions, the Family Health Strategy (FHS). OBJECTIVE: We will evaluate the effects of socioeconomic determinants, BFP exposure and FHS coverage on HIV/AIDS incidence, treatment adherence, hospitalizations, case fatality, and mortality using unprecedently large aggregate and individual-level longitudinal data. Moreover, we will integrate the retrospective datasets and estimated parameters with comprehensive forecasting models to project HIV/AIDS incidence, prevalence and mortality scenarios up to 2030 according to future socioeconomic conditions and alternative policy implementations. METHODS AND ANALYSIS: We will combine individual-level data from all national HIV/AIDS registries with large-scale databases, including the "100 Million Brazilian Cohort", over a 19-year period (2000-2018). Several approaches will be used for the retrospective quasi-experimental impact evaluations, such as Regression Discontinuity Design (RDD), Random Administrative Delays (RAD) and Propensity Score Matching (PSM), combined with multivariable Poisson regressions for cohort analyses. Moreover, we will explore in depth lagged and long-term effects of changes in living conditions and in exposures to BFP and FHS. We will also investigate the effects of the interventions in a wide range of subpopulations. Finally, we will integrate such retrospective analyses with microsimulation, compartmental and agent-based models to forecast future HIV/AIDS scenarios. CONCLUSION: The unprecedented datasets, analyzed through state-of-the-art quasi-experimental methods and innovative mathematical models will provide essential evidences to the understanding and control of HIV/AIDS epidemic in LMICs such as Brazil.