title: Antiviral combinations for severe influenza.
abstract: 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.
authors.affiliation: Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Jake
authors.initials: J
authors.lastname: Dunning
authors.affiliation: Division of Genetics and Genomics, The Roslin Institute, Easter Bush, Midlothian, UK.
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Baillie
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address: fgh@virginia.edu.
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hayden
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007251:Influenza, Human / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors