Observational data suggest that the treatment of
influenza infection with
neuraminidase inhibitors decreases progression to more severe illness, especially when treatment is started soon after symptom onset. However, even early treatment might fail to prevent complications in some patients, particularly those infected with novel viruses such as the 2009 pandemic
influenza A H1N1,
avian influenza A H5N1 virus subtype, or the
avian influenza A H7N9 virus subtype. Furthermore, treatment with one
antiviral drug might promote the development of
antiviral resistance, especially in immunocompromised hosts and
critically ill patients. An obvious strategy to optimise
antiviral therapy is to combine drugs with different modes of action. Because host immune responses to
infection might also contribute to illness pathogenesis, improved outcomes might be gained from the combination of
antiviral therapy with drugs that modulate the immune response in an infected individual. We review available data from preclinical and clinical studies of combination
antiviral therapy and of combined
antiviral-
immunomodulator therapy for
influenza. Early-stage data draw attention to several promising
antiviral combinations with therapeutic potential in severe
infections, but there remains a need to substantiate clinical benefit. Combination
therapies with favourable experimental data need to be tested in carefully designed aclinical trials to assess their efficacy.