Spillover Benefit of Pre-Exposure Prophylaxis for HIV Prevention: Evaluating the Importance of Effect Modification using an Agent-Based Model

We developed an agent-based model using a trial emulation approach to quantify effect measure modification of key variables on spillover effects of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in Atlanta, GA. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomized trial with eligible components (≥3 agents and ≥1 HIV+ agent) first randomized to intervention or control (no PrEP). Within intervention components, agents were randomized to PrEP with intervention coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component level characteristics and estimated spillover effects using an extension of randomization-based estimators. We observed an attenuation of the spillover effect when agents were in components with a higher prevalence of either drug use or bridging potential (if an agent acts as a mediator between ≥2 connected groups of agents). The estimated spillover effects were larger in magnitude among components with either higher HIV prevalence or greater density (number of existing compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.