Analytical and numerical analysis of spillover effects in prioritized PrEP for HIV prevention

Abstract: Pre-exposure prophylaxis (PrEP) is a highly effective intervention for preventing HIV transmission, but its high cost and uneven uptake raise challenges. While spillover effects - wherein PrEP use in one group reduces infections in others - are known to occur, they remain poorly quantified and rarely guide policy. We develop and analyze a novel compartmental HIV model that stratifies the population into three interacting subgroups: heterosexual males (HETM), heterosexual females (HETF), and men who have sex with men (MSM). We derive standard results, including the control reproduction number, and establish conditions for local and global stability of the disease-free equilibrium. We provide a closed-form, time-resolved expression for the spillover-adjusted number needed to treat (NNT), a measure of the population-level impact of PrEP uptake in one group on incidence in others. Simulations calibrated to Georgia state-level data reveal that PrEP delivery to MSM yields substantial indirect benefits, particularly for HETF, where the spillover effect exceeds the direct effect by a factor of five. We extend the baseline model to include risk stratification within HETF, showing that targeting high-risk HETF outperforms direct PrEP delivery to HETM, emphasizing the importance of intra-group heterogeneity. To evaluate whether these findings persist under more detailed assumptions, we embed our framework into the national HOPE model maintained by the CDC and conduct global sensitivity analysis using Sobol indices. This approach extends our analytical insights and quantifies how uncertainty in PrEP allocation strategies propagates through complex dynamics. Our results show that moderately complex, analytically tractable models can yield realistic and actionable guidance for HIV control-capturing nonlinear spillover dynamics in ways that remain interpretable even in high-dimensional settings.