Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice.
Control of highly pathogenic avian H5N1 influenza viruses is a major public-health concern. Antiviral drugs could be the only option early in the pandemic.METHODS. BALB/c mice were given oseltamivir (0.1, 1, or 10 mg/kg/day) twice daily by oral gavage; the first dose was given 4 h before inoculation with H5N1 A/Vietnam/1203/04 (VN1203/04) virus. Five- and 8-day regimens were evaluated.RESULTS. Oseltamivir produced a dose-dependent antiviral effect against VN1203/04 in vivo (P<.01). The 5-day regimen at 10 mg/kg/day protected 50% of mice; deaths in this treatment group were delayed and indicated the replication of residual virus after the completion of treatment. Eight-day regimens improved oseltamivir efficacy, and dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively (P<.05). Overall, the efficacy of the 5- and 8-day regimens differed significantly (death hazard ratio, 2.658; P<.01). The new H5N1 antigenic variant VN1203/04 was more pathogenic in mice than was A/HK/156/97 virus, and a prolonged and higher-dose oseltamivir regimen may be required for the most beneficial antiviral effect.CONCLUSIONS. Oseltamivir prophylaxis is efficacious against lethal challenge with VN1203/04 virus in mice. Viral virulence may affect the antiviral treatment schedule.
Yen
Hui-Ling
HL
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Monto
Arnold S
AS
Webster
Robert G
RG
Govorkova
Elena A
EA
D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001921:Brain / Q000821:virology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006146:Guanidines; D009980:Influenza A virus / Q000187:drug effects* / Q000472:pathogenicity*; D020128:Inhibitory Concentration 50; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D053139:Oseltamivir; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology; D014774:Virulence; D014779:Virus Replication / Q000187:drug effects; D053243:Zanamivir
D000081:Acetamides; D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D053243:Zanamivir