July 1, 2009 The Pump Handle 1Comment

by revere, cross-posted from Effect Measure

Currently the only antiviral drugs effective against the swine flu (novel H1N1) virus are the two neuriminidase inhibitors, oseltamivir (trade name Tamiflu) and zanamivir (trade name Relenza). Relenza is in active form at the outset and cannot be absorbed orally. It must be inhaled, leading to asthmatic reactions in some, ineffective dosage in those with breathing difficulties, and no drug at sites beyond the respiratory tract. Despite these drawbacks, it has so far produced little or no viral resistance. Tamiflu is absorbed orally and converted by the liver into the active form, so it gets to other organs and can be taken by people unable to inhale Relenza. But it has other problems. One is a tendency for the flu virus to become resistant to it. Until today, however, there have been no reports of Tamiflu resistance in swine flu isolates, although most flu experts were waiting for the other shoe to drop. Today may have been the day we heard it fall:

Scientists have established the first case of the new H1N1 influenza strain showing resistance to Tamiflu, the main antiviral flu drug, Danish officials and the manufacturer said on Monday.It was expected that the strain would at some point show resistance to Tamiflu, Denmark’s State Serum Institute said. The patient was now well and no further infection with the resistant virus had been detected.

“It does not constitute a risk to public health and does not cause changes to the recommendations for the use of oseltamivir (Tamiflu),” the institute said in a statement. (Reuters)


It’s not exactly clear what a lack of risk to public health means in this context. I agree at this point it doesn’t affect the extent of infection in the population, but if Tamiflu resistance becomes widespread it will alter treatment options for those who are infected and since Tamiflu treatment can reduce viral shedding also affect transmission within small groups, like households. Still, we don’t know much about the reported resistance. Seasonal H1N1 is already resistant, so if novel H1N1 reassorted and swapped out its own H1 for a seasonal H1 when both viruses co-infect a host cell, that would be one mechanism. More likely, the HA of the the swine flu virus suffered a mutation that produces Tamiflu resistance (H274Y is the commonest, but others are possible). We don’t know any details yet.

Details aside, this development is not a surprise, although its ultimate significance is unclear. Antivirals, especially when given early in the course of the illness, do seem to be of some benefit, but it’s not dramatic. They reduce the symptomatic duration of illness by a day or two and with it viral shedding. They may also have some prophylactic effect for those known to be exposed. But if your model is the often dramatic effect that antibiotics have on bacterial infections, these antivirals are effective only on the margins and they are not without adverse reactions.

So the other shoe may have dropped but if it did, we don’t yet know the consequences. People get over flu because their bodies are able to do it on their own. For some, although not most, an antiviral might make a vital difference. But the main protections are not to get infected to begin with, and if you do, to be in good shape, to have good care, and to have good luck. If you have the last of these, you don’t need antivirals. If you don’t, they probably won’t help.

Meanwhile, it is what it is. Whatever that is.

One thought on “Swine flu and Tamiflu resistance

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