CANNES, France, April 29 -- Using single antiviral drugs to treat the current outbreak of swine influenza could result in the development of a resistant strain, a leading flu researcher said here.
The H1N1 virus currently infecting humans around the globe is already resistant to one of the two classes of antiviral medications, the adamantanes (rimantadine and amantadine).
The virus is, however, susceptible to the neuraminadase inhibitors, oseltamivir (Tamiflu) and zanamivir (Relenza).
The risk is high that a strain resistant to all of these drugs could develop as long as the disease continues to be treated with single medications, Robert Webster, Ph.D., of St. Jude Children's Research Hospital in Memphis, said at the conference on Influenza Vaccines for the World.
"We can't continue to use single antiviral drugs. . . . The virus will win the game," he said.
He said he couldn't guess how long it would take for resistance to occur, "but if you use a mono drug you will get resistance."
The increased risk is compounded by the background resistance that develops spontaneously by mutation, he said.
For example, up to 67% of seasonal H1N1 influenzas in Norway were resistant to oseltamivir during the 2007-2008 flu season, according to Jennifer McKimm-Breschkin, Ph.D., of CSIRO Molecular & Health Technologies in Australia.
This occurred even though Norwegian doctors made very little use of oseltamivir, illustrating the ability of resistance to develop without any drug treatment.
More drug exposure might enable these resistant viruses to become the predominant strain more rapidly, she said.
She noted that during the following winter in the southern hemisphere, oseltamivir-resistance reached a prevalence of 93% in Australia and 100% in South Africa.
Dr. Webster suggested that drug combinations would be the best strategy for avoiding this problem, a lesson learned, he said, from HIV.
"We know all the ground rules. With an RNA virus you need two, three, or four drugs in combination," he said.
But, he noted, "we haven't got them yet for flu. . . . That's the bottom line."
In his laboratory, adding ribavirin to the neuraminadase inhibitors has yielded some additional benefit, but ribavirin is not approved for use against flu.
Other drugs, such as monoclonal antibodies and immune system modulators, might also be used in combination to help control the immune response to infection, he said.
But until some of these combinations are proven and approved for use, he said treatment of potential pandemic flu viruses, including the swine flu, would have to continue with the single antivirals.
"At the moment, we don't have an option," he said.
Dr. McKimm-Breschkin noted that regulatory authorities and the health community now recommend a diversified antiviral stockpile of oseltamivir and zanamivir, which she said would attenuate the risk of resistance.
