title: Combination antiviral therapy for influenza: predictions from modeling of human infections.
abstract: Emergence of resistance is a major concern in influenza antiviral treatment and prophylaxis. Combination antiviral therapy might overcome this problem. Here, we estimate that all possible single mutants and a sizeable fraction of double mutants are generated during an uncomplicated influenza infection. While most of them may sustain a fitness cost, some variants may confer drug resistance and be selected during therapy. We argue that a triple combination regimen would markedly reduce the risk of antiviral resistance emergence in seasonal and pandemic influenza viruses, especially in seriously ill or immunocompromised hosts.
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA. asp@lanl.gov
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Libin
authors.initials: L
authors.lastname: Rong
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hayden
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology*; D008962:Models, Theoretical; D009154:Mutation; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D012641:Selection, Genetic
chemical_list: D000998:Antiviral Agents