Research emphasises the role that social structures play in shaping national HIV prevalence. This study examined how social, economic, and political contexts that may represent the confluence of individual capabilities and environmental affordances or constraints are associated with national HIV prevalence. Based on social-ecological perspectives, we examined social-structural dimensions in relation to national HIV prevalence. The study identified six publicly available nation-level social, political, and economic indices and examined their associations with national 2009 HIV prevalence across 225 nations. National indices, (a) education expenditures, (b) unemployment rate, (c) homicide rate, (d) freedom of religion, and (e) women's social rights, altogether explained 43% of the variability in national HIV prevalence. Education expenditures, homicide rate, and freedom of religion were significant predictors of national HIV prevalence in the multivariate analysis. The present study identified nation-level factors that capture social, economic, and political contexts to explain between-nation differences in HIV prevalence. Findings extend current literature on the social-structural foundation of HIV-risk and the relationship between human rights and health. National safeguards that afford individuals the power to promote general quality of life and protection from structural violence may be most important to lowering overall rates of HIV transmission.