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The emergence of resistance to antiviral action poses a major limitation to the use of antivirals, as for other antimicrobials. Thus in the case of influenza, the emergence of amantadine/rimantadine-resistant seasonal influenza viruses, A(H3N2) viruses, by acquisition of a resistance mutation, and A(H1N1)pdm09 viruses, by the acquisition of a resistant M gene from the parental Eurasian swine virus, has rendered amantadine and rimantadine of no value against currently circulating human influenza viruses.

Whereas resistance usually emerges as a result of selective drug pressure during treatment, it appears that the oseltamivir resistance which emerged in the previous seasonal A(H1N1) viruses in 2007 was the result coincidentally of an adaptive (fitness) mutation in the epidemic virus which was maintained in the absence of drug pressure. These events emphasise the relative ease with which influenza viruses may acquire resistance to antivirals, via mutation or genetic reassortment, and stress the importance of sustained surveillance of antiviral susceptibility, and of the need for developing additional antiviral agents with complementary resistance profiles, which may be of use in combination therapy to reduce the potential for resistance emergence.  

This section focuses on antivirals approved for use against influenza and includes information on the mechanisms of antiviral action and resistance, methods for assessing changes in antiviral susceptibility, suitable for surveillance, and in vivo studies (animal model and clinical) to assess the consequences of reduced susceptibility of viruses on the effectiveness of antiviral treatment.