Beyond Economic Determinism: Epidemic Scale, Gender Disparities, and Population-Level Health System Outcomes in the Global Human Immunodeficiency Virus Response (2024)

Abstract Background Despite major global investments in HIV program, HIV remains a leading cause of mortality globally, with approximately 39 million people living with HIV and over 630,000 HIV-related deaths reported in 2024. Substantial cross-national variation in HIV-related mortality persists. While national wealth is a recognized determinant of survival, less is known about how epidemic scale, population-level health system functioning, and gender disparities jointly shape mortality outcomes in the contemporary treatment era. Objective This study examined the extent to which national wealth, epidemic scale, and population-level health system outcomes are associated with HIV-related mortality across countries, and assessed gender-specific disparities in HIV mortality and infection, including discordance between infection burden and mortality outcomes. Methods A cross-national ecological analysis of 105 countries with established HIV epidemics using 2024 data from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Bank was conducted. HIV mortality-to-prevalence ratios were analyzed in relation to GDP per capita, epidemic scale (people living with HIV), and world region using multivariable log-linear regression models with heteroskedasticity-robust (HC3) standard errors. Model-based standardized residuals were examined to identify countries with higher- or lower-than-expected mortality. Gender-disaggregated analyses assessed regional heterogeneity and discordance between HIV infection and mortality by sex. Results HIV mortality-to-prevalence ratios varied widely across countries (median 1.37%; range 0.10–7.62%). Higher GDP per capita was independently associated with lower HIV mortality (β = −0.19, p = 0.008), while larger epidemic scale was also associated with reduced mortality intensity (β = −0.13, p = 0.001). The multivariable model explained 44.5% of cross-country variation. Residual analyses identified both positive deviance and marked underperformance across regions and income levels. Globally, mean HIV mortality did not differ significantly between men and women; however, pronounced regional heterogeneity was observed. A male disadvantage paradox, higher male mortality despite lower infection burden was evident in several countries and was strongly associated with lower national wealth (ρ = −0.70, p < 0.001). Conclusions HIV mortality in 2024 reflects not only economic resources but also differences in epidemic scale, population-level health system outcomes, and gender-related inequities. Addressing persistent mortality gaps will require public health strategies that prioritize equity, system adaptation, and gender-responsive HIV responses beyond reliance on national wealth alone.