Background: The evolution of antiviral drug resistance during influenza pandemics has created widespread concern. Use of antiviral drugs is a main contributor to the evolution of drug-resistant strains. Moreover, there are recent examples of influenza viruses acquiring drug resistance seemingly without incurring a fitness penalty that reduces their transmission rate. This creates the possibility of strategic (game theoretical) interaction between jurisdictions making decisions about use of antiviral drug stockpiles.

Methods: We developed and analyzed a 2-player 2-strategy game theoretical model. Each ‘player’ (an authority in a health jurisdiction) can choose to treat with antiviral drugs at a low rate or a high rate. High treatment rates are more likely to cause emergence of a drug-resistant strain, and once a drug-resistant strain has evolved, it can spread between the two jurisdictions. We determine the Nash equilibria of the game.

Results: We show that there is a coordination game between the jurisdictions, where both players choosing a low treatment rate, or both choosing a high treatment rate, are the only stable outcomes. The socially optimal outcome occurs if both players cooperate by choosing a low treatment rate, thereby avoiding generating drug-resistant mutants. However, such cooperation may fail to materialize if the jurisdictions are closely connected through travel; if the drug-resistant mutant is tolerated (not seen as undesirable); or if the antiviral drug has partial efficacy against transmission of the drug-resistant strain.

Conclusions: Inter-jurisdictional cooperation could be essential during a severe influenza pandemic, but we know little about how jurisdictions will interact in a scenario where highly pathogenic, drug-resistant mutant strains are able to transmit as effectively as non-resistant strains. Therefore, strategic multi-population interactions during influenza pandemics should be further studied.