Do Our Flu Antivirals Work on H5N1?

With avian influenza A (H5N1) infecting more mammals than ever before -- including U.S. dairy cattle -- infectious disease experts are paying close attention to whether current influenza antivirals would be effective should H5N1 adapt to humans.

All influenza viruses have extremely similar internal mechanisms for reproduction, William Schaffner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and a spokesperson for the Infectious Diseases Society of America (IDSA), told MedPage Today. So if an antiviral works against one strain, it will also work on other strains, he said.

"Everything I've heard from the CDC and elsewhere ... is that the antivirals that we have available today will work against H5N1. And that's consistent with the effect of the antivirals against past avian influenza strains," Schaffner said.

This includes neuraminidase inhibitors, such as oseltamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab), as well as the polymerase inhibitor baloxavir (Xofluza). While neuraminidase inhibitors interfere with the enzyme that allows a virus to cleave itself off an infected cell in order to spread, polymerase inhibitors interfere with replication at the level of messenger RNA.

The CDC is working in the lab "to better characterize the virus from the human case in Texas," and the agency "completed susceptibility testing for the most common class of influenza antiviral medications that are used for seasonal influenza," a spokesperson for the CDC's Center for Global Health told MedPage Today.

The testing confirmed that "the H5N1 virus was susceptible to all commercially available FDA-approved and recommended neuraminidase inhibitors," the spokesperson said. Testing to confirm the susceptibility of a different type of antiviral medication is ongoing since it takes longer, he added.

Interim CDC guidance suggests initiating antiviral treatment with a neuraminidase inhibitor as early as possible for symptomatic outpatients, and using oseltamivir to treat severe, progressive, or complicated H5N1. For people who meet the epidemiologic exposure criteria, oseltamivir also is recommended as prophylaxis.

Still, Schaffner noted that "antivirals are by no means a panacea."

Andrew Pavia, MD, professor and chief of the division of pediatric infectious diseases at the University of Utah in Salt Lake City, said that while evidence indicates oseltamivir would be effective, "effective doesn't mean it's an ideal drug." For instance, oseltamivir, like other antivirals, is most effective if taken in the first 48 hours, which can be a difficult window to catch.

There are many other unknowns about treating H5N1 with antivirals, such as whether antivirals would have clinical benefit or if resistance would develop. "We don't know the answer because we have not seen a lot of human infections with this particular strain of H5N1," Pavia said. Some experts have questioned whether the U.S. has been adequately testing for H5N1.

The U.S. has a large stockpile of oseltamivir but has less of newer drugs like baloxavir, which has a different mechanism and could be vital if oseltamivir resistance became a problem, Pavia said. In terms of using a combination of drugs, he said there have not been studies showing clear benefits, though that's something the research community is pursuing.

In terms of other potential treatments, a trio of vaccines has already been developed and approved, and last year Via Nova Therapeutics received an FDA Investigational New Drug application for a nucleoprotein inhibitor, VNT-101.

"H5N1 has been behaving in ways that we didn't expect which means that we know we have to watch it very carefully," Pavia said. "That doesn't mean we know what it's going to do, but it means we have to have a lot of humility and invest some real resources in studying it and watching it."

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