Disseminated Effects in Agent-Based Models: A Potential Outcomes Framework and Application to Inform Preexposure...

Preexposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection may benefit not only the person who uses it but also their uninfected sexual risk contacts. We developed an agent-based model using a novel trial emulation approach to quantify disseminated effects of PrEP use among men who have sex with men in Atlanta, Georgia, from 2015 to 2017. Model components (subsets of agents connected through partnerships in a sexual network but not sharing partnerships with any other agents) were first randomized to an intervention coverage level or the control group; then, within intervention components, eligible agents were randomized to receive or not receive PrEP. We calculated direct and disseminated (indirect) effects using randomization-based estimators and report corresponding 95% simulation intervals across scenarios ranging from 10% coverage in the intervention components to 90% coverage. A population of 11,245 agents was simulated, with an average of 1,551 components identified. When comparing agents randomized to no PrEP in 70% coverage components with control agents, there was a 15% disseminated risk reduction in HIV incidence (risk ratio = 0.85, 95% simulation interval: 0.65, 1.05). Persons not on PrEP may receive a protective benefit by being in a sexual network with higher PrEP coverage. Agent-based models are useful for evaluating possible direct and disseminated effects of HIV prevention modalities in sexual networks.