OBJECTIVES: Efforts to combat COVID-19 have largely focused on vaccination and non-pharmaceutical interventions to decrease hospitalization and death and to reduce transmission. First generation COVID-19 direct-acting antivirals (DAAs) are only authorized for high-risk patients to reduce individual risk of disease progression. However, DAAs can also impact transmission by reducing viral load, thereby shortening the duration of infectivity. Next generation oral DAAs in development may have safety profiles that are amenable to broader eligibility and use. This analysis estimates the economic and clinical impact of increasing the utilization of DAAs to treat COVID-19.

METHODS: A susceptible-infected-recovered-susceptible model was developed to estimate COVID-19-related outcomes based on DAA uptake. Cost-savings modeled included reduced healthcare utilization amongst individual patients and, importantly, potential savings attributable to reduced transmission. Cost inputs included treatment acquisition costs, adverse events, healthcare utilization, and productivity losses based on published literature. One million individuals were assessed with clinical and economic outcomes estimated for DAA adoption by risk level.

RESULTS: The model projects 402,330 new infections per 1 million individuals annually, leading to 6,000 hospitalizations and 107 deaths. By increasing DAA use by 10% in the high-risk population and 20% in the standard-risk population, infections decreased to 312,000, with 1,800 fewer hospitalizations and 34 fewer deaths. Decreases in medical encounters were driven by reduction in transmission (77% of the decrease) and reduction in severity amongst those treated (23% of the decrease). Among deaths averted, 72% were attributable to the reduction in transmission. Overall, costs decrease by 23.5% with increased treatment.

CONCLUSIONS: This study is among the first to model the potential population-level impact of DAAs in reducing infectivity and transmission, a factor currently under-emphasized in the literature. New DAAs under development with potentially improved safety profiles may expand the uptake of treatment and substantially reduce the clinical and economic burden of COVID-19.