Influenza and Antiviral Resistance: an Overview

Influenza affects approximately 1 billion individuals each year resulting in between 290,000 and 650,000 deaths. Young children and immunocompromised individuals are at a particularly high risk of severe illness attributable to influenza and these are also the groups of individuals in which reduced susceptibility to neuraminidase inhibitors is most frequently seen. High levels of resistance emerged with previous adamantane therapy for influenza A and despite no longer being used to treat influenza and therefore lack of selection pressure, high levels of adamantane resistance continue to persist in currently circulating influenza A strains. Resistance to neuraminidase inhibitors has remained at low levels to date and the majority of resistance is seen in influenza A H1N1 pdm09 infected immunocompromised individuals receiving oseltamivir but is also seen less frequently with influenza A H3N2 and B. Rarely, resistance is also seen in the immunocompetent. There is evidence to suggest that these resistant strains (particularly H1N1 pdm09) are able to maintain their replicative fitness and transmissibility, although there is no clear evidence that being infected with a resistant strain is associated with a worse clinical outcome. Should neuraminidase inhibitor resistance become more problematic in the future, there are a small number of  alternative novel agents within the anti-influenza armoury with different mechanisms of action to neuraminidase inhibitors and therefore potentially effective against neuraminidase inhibitor resistant strains. Limited data from use of novel agents such as baloxavir marboxil and favipiravir, does however show that resistance variants can also emerge in the presence of these drugs.