Antivirals are an important defence against novel strains of influenza. However, the impact of widespread drug usage on strain circulation across multiple epidemic waves - via their impact on host immunity - is unknown despite antivirals having the likelihood of extensive use during a pandemic. To explore how drug usage by individuals affects population strain dynamics, we embedded a two-strain model of within-host dynamics within an epidemic model. We found that when 40% of hosts took drugs early during the infectious period, transmission was reduced by 30% and average levels of immunity by 2·9-fold (comparable to antibody concentrations), relative to 14% and 1·5-fold reductions when drugs were taken late. The novel strain was more successful relative to the resident strain when drugs were not taken, and an intermediate level of drug coverage minimized incidence in subsequent waves. We discuss how drug regimens, coverage and R 0 could impact pandemic preparedness.