Genetic Diversity of RNA Viruses

Volume 176 of the series Current Topics in Microbiology and Immunology pp 119-130

Emergence and Transmission of Influenza A Viruses Resistant to Amantadine and Rimantadine

  • F. G. HaydenAffiliated withDepartments of Internal Medicine and Pathology, University of Virginia Health Sciences Center
  • , A. J. HayAffiliated withVirology Division, National Institute for Medical Research

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Many clinical studies have documented the efficacy of amantadine and rimantadine for prophylaxis and treatment of influenza A virus infections (Douglas 1990; Tominack and Hayden 1987). Antiviral activity has been demonstrated in various animal models of influenza (Hayden 1986) and during clinical use in humans (Douglas 1990). Amantadine- and rimantadine-resistant mutants have been recovered during studies in mice (Oxford et al. 1970, Oxford and Potter 1972), birds (Webster et al. 1985; Beard et al. 1987; Bean et al. 1989), and recently in children and adults treated with these drugs (Hall et al. 1987; Thompson et al. 1987; Belshe et al. 1988; Hayden et al. 1989). The impact of drug resistance on the clinical usefulness of these drugs is thus of obvious concern. Factors which may influence the clinical importance of drug-resistant viruses include their frequency and rapidity of emergence, genetic stability, transmissibility, pathogenicity, and ability to compete epidemiologically with wild-type viruses (Bean et al. 1989). The following sections review the limited information available from animal and human studies that address these characteristics and the correlation of these factors with particular resistance mutations.