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Further Reports of Tamiflu Resistance in Avian Flu Virus Pending: Expert

Posted on: Saturday, 15 October 2005, 18:00 CDT

By HELEN BRANSWELL

TORONTO (CP) - There is additional, unpublished evidence of resistance to the anti-flu drug Tamiflu in human cases of H5N1 avian influenza, an U.S. expert in antiviral drugs hinted Saturday.

Dr. Frederick Hayden suggested data that have not yet hit scientific literature point to the existence of more cases where H5N1 viruses evaded the drug that countries around the world have been stockpiling as a hedge against a feared pandemic.

"There's other information that's not in the public domain right now," Hayden, a professor of clinical virology at the University of Virginia, said in an interview.

Hayden is co-chair of an international scientific group that closely monitors for emergence of viral resistance to neuraminidase inhibitors - the drug class to which Tamiflu belongs. He would not elaborate on how many cases may have been discovered.

Scientific and medical journals typically refuse to publish previously disseminated material, so researchers carefully guard new data until publication.

"I feel comfortable with the statement that was in the report that we put out from the Hanoi meeting . . . I think what the statement was 'several cases,' " he said.

The meeting Hayden referred to was a World Health Organization-staged gathering of international influenza experts that took place in Hanoi from May 10-12.

The report of that meeting, published late last month in the New England Journal of Medicine, contains a brief reference to drug-resistant viruses having been isolated "recently in several patients . . . who were treated with oseltamivir" - Tamiflu's generic name.

A footnote attached to the statement refers to a report of a previous WHO meeting of flu experts, held in Manila from May 6-7.

The Manila meeting report contains information on only a single case where Tamiflu-resistant virus was recovered from an H5N1 patient. That case, a 14-year old Vietnamese girl who fell ill in late February, is currently the only publicly acknowledged finding of a Tamiflu-resistant virus.

A detailed analysis of viral clones grown from a specimen taken from the Vietnamese girl was released Friday by the journal Nature.

There was some initial confusion attached to the publication, which a number of experts felt represented new evidence of resistance to the drug.

Dr. Yoshihiro Kawaoka, senior author on the Nature paper, had not been at either WHO meeting, nor had he read the report of the Manila meeting. He confirmed Saturday that the virus he and his collaborators studied bore the same identification number as the one reported on at the Manila meeting.

"It must be the same virus," he said.

The analysis Kawaoka and his co-authors produced showed that while the girl's virus was at least partially resistant to Tamiflu, it was fully susceptible to another neuraminidase inhibitor, zanamivir.

The authors suggested their findings point to the practicality of adding zanamivir -which is sold as Relenza by GlaxoSmithKline - to national pandemic stockpiles.

Some countries, notably the United States and Germany, have done so. But Relenza has never made huge inroads with consumers and is made in limited quantities.

Source: Canadian Press

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