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 spillover effects of pre-exposure prophylaxis (PrEP) for HIV among men who have sex with men (MSM) in the Atlanta-Sandy Springs-Roswell metropolitan area, Georgia. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomised trial with eligible components (≥3 agents with ≥1 HIV+ agent) first randomised to intervention or control (no PrEP). Within intervention components, agents were randomised to PrEP with coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component-level characteristics and estimated spillover effects on HIV incidence using an extension of randomisation-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 partnerships compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.