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Efficacy of Oseltamivir Against H5N1

By Eric Toner, M.D., July 26, 2005

A study released last week in The Journal of Infectious Diseases indicates that standard oseltamivir dosing may not be sufficient for the current strain of H5N1 in Southeast Asia. Researchers Yen, Monto, Webster and Govorkova report on a mouse study that tested the efficacy of oseltamivir (Tamiflu), a neuraminidase inhibitor, against H5N1 avian influenza virus that was isolated from a fatally infected victim of the current outbreak in Vietnam. The study’s results reveal important information about both the virulence of the H5N1 virus and the efficacy of oseltamivir.

The researchers administered oseltamivir 4 hours prior to inoculation with 5x the observed LD50 of the virus. While all of the placebo-treated controls died, 50% of the mice treated for 5 days with a dose equivalent to the recommended human treatment dose of 75 mg b.i.d. survived. When this dose was continued for 8 days, the survival rate increased to 80%. Virus titer studies done at 3 day intervals indicated that the drug was effectively suppressing the infection as long as it was being administered, and that treated mice died as a result of uncontrolled infection upon discontinuation of treatment.

The results of this study demonstrate that the optimal dosing schedule of oseltamivir depends on the virulence of a particular strain of influenza virus and that while oseltamivir is clearly effective against this particular virus, the standard recommended regimen may not be sufficient to treat (and prevent disease) in exposed individuals. Further research is required to define the optimal antiviral treatment schedule, but standard regimens based on common human influenza strains cannot be relied upon in the face of a novel virus. Physicians must consider the possibility that current recommendations for dose and course of treatment may not be efficacious in the face of an influenza pandemic, and both may need to be increased.

Because it is estimated that it will take at least 6 months to produce a significant supply of vaccine in the face of a pandemic, it is critical that the optimum dose and duration of treatment with antivirals be determined as quickly as possible. In the face of pandemic influenza, antivirals will be the only available defense, and they will have to be used efficiently given their limited supply.

Reference

  1. Yen HL, Monto AS, Webster RG, Govorkova EA. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic a/vietnam/1203/04 influenza virus in mice. J Infect Dis. Aug 15 2005;192(4):665-672.