Questions about tamiflu resistance

Jackie (from Cambodia) recently sent me a question regarding the recent news about influenza viruses being more resistant to tamiflu and whether this might have an impact on our own staff safety plans and guidelines. As it so happens, we have a new a Senior Director for Health Programs from CARE USA, Dr. Benjamin Schwartz who also happens to be an expert in pandemic influenza issues! He previously worked at HHS (Department of Health and Human Services) and CDC. He was the lead at HHS for pandemic vaccine and antiviral drug planning and the author of the national recommendations on antiviral drug use. So, I've asked Ben to answer Jackie's question

From Ben:

“The emergence and spread of Tamiflu resistant influenza viruses have led to questions on whether pandemic planning and preparedness should change. Before answering those questions, it's important to understand a bit about antiviral drug resistance among influenza viruses. Resistance occurs due to a chance mutation occurring at the active site where the neuraminidase inhibitor drug (e.g., Tamiflu) binds to the virus. Historically, resistant viruses did not spread between people because the mutation also reduced the fitness of the virus, reducing its transmissibility. The newly emerged resistant virus (which can spread between people) is a specific influenza A (H1N1) clone that has a mutation not only at the neuraminidase inhibitor active site but also another "compensatory" mutation that restores the virus's fitness. All other circulating influenza viruses - with the exception of this H1N1 clone - remain susceptible to Tamiflu. The resistance mutations cannot spread from one influenza virus to another; and the likelihood of these mutations developing in another influenza virus is very small.

Given this understanding, the emergence of the resistant H1N1 has no direct implications on whether a pandemic virus may become resistant to Tamiflu to or Relenza (the other antiviral drug in the same neuraminidase inhibitor class). A fit and resistant pandemic influenza virus remains highly unlikely. U.S. policy on antiviral drug stockpiling and plans for pandemic use have not changed (and in fact, antiviral drug recommendations recently were expanded to include preventive ["prophylactic"] use). Some have suggested stockpiling Relenza rather than Tamiflu. However, there is an FDA warning on the use of Relenza in people with airway disease such as asthma or emphysema and there is not the same body of evidence that Relenza is effective in preventing severe or fatal influenza seasonally or with H5N1 (whereas such data do exist for Tamiflu). The U.S. national stockpile includes 80% Tamiflu and 20% Relenza. Such diversification may be prudent. If the proposed antiviral drug use strategy is prevention (as opposed to treatment), both drugs have been equally effective and a greater proportion of Relenza could be considered. If there are any questions about strategy or drug choice, I'd be glad to provide further thoughts.”