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Influenza Antiviral Drug Resistance
NOTE: The information in this document is based on flu activity as of April 5, 2008. This document will be updated as needed as the flu season progresses.
What is antiviral resistance?
Antiviral resistance means that a virus has changed in such a way that the antiviral drug is less effective in treating or preventing illnesses caused by the virus.
In the United States, four antiviral drugs are FDA-approved for use against influenza: amantadine, rimantadine, zanamivir and oseltamivir. However, amantadine and rimantadine (the adamantane drugs) are NOT recommended for use in the United States during the 2007-08 influenza season because many recent influenza viruses are resistant to these drugs. The adamantane drugs are approved for influenza A while the neuraminidase inhibitor drugs zanamivir and oseltamivir are approved for influenza A and influenza B.
How does antiviral resistance happen?
Influenza viruses constantly change as the virus makes copies of itself (i.e. replicates). The ability to constantly change is a hallmark of influenza viruses. Flu viruses often change from one season to the next or they can even change within the course of one flu season. Some changes can result in the viruses being resistant to one or more of the antiviral drugs that are used to treat or prevent influenza.
How is antiviral resistance detected?
Samples of viruses collected from around the United States and worldwide are studied to determine if they are resistant to any of the four FDA-approved influenza antiviral drugs. CDC routinely collects viruses through a domestic and global surveillance system to monitor for changes in influenza viruses.
What has CDC done to improve monitoring of influenza viruses for antiviral resistance?
In the last two years, CDC has improved the ability to rapidly detect and monitor for resistant viruses.
How is this surveillance information used?
Virus surveillance information is helpful in making recommendations for how to treat or prevent flu. For example, during the 2005-06 season, data showed that many U.S. influenza viruses were resistant to the adamantane class of drugs, amantadine and rimantadine. This information led CDC to recommend against the use of the adamantanes for treatment and prevention of influenza during that influenza season and continuing through the 2007-08 season. Monitoring is continuing for resistance to the adamantane drugs to see if the proportion of flu viruses that are resistant is changing.
What have we seen so far during the 2007-2008 season in terms of antiviral resistance monitoring or surveillance in the United States?
CDC laboratory surveillance has indicated continued high resistance among influenza virus isolates to the adamantanes (amantadine and rimantadine) in the United States. As of April 5, 2008, 99.6% of influenza A (H3N2) viruses and 11.1% of influenza A (H1N1) viruses were resistant to the adamantanes. Because of high levels of resistance, CDC recommends that adamantanes not be used to treat or prevent influenza infections at this time. The adamantanes have no activity against influenza B viruses.
Also as of April 5, 2008, CDC has detected 10.2% of H1N1 viruses tested were resistant to the antiviral drug oseltamivir (brand name Tamiflu®). No oseltamivir resistant influenza A (H3N2) or B viruses have been found in the United States this season and resistance to zanamivir has not been detected. Because resistance to oseltamivir remains low and only has been detected among H1N1 viruses, and because H3N2 and B viruses are now predominant in the U.S., CDC continues to recommend that oseltamivir and zanamivir be used to treat and prevent influenza.
CDC continues to track this information and updated antiviral resistance figures are available in the Weekly U.S. Influenza Surveillance Report, FluView.
Are a lot of U.S. viruses resistant to oseltamivir?
As of April 5, 2008, 8.3% of all influenza A and B viruses analyzed by CDC this season have been found to be resistant to oseltamivir. Of those, 10.2% of H1N1 viruses and 0% of H3N2 and B viruses have been resistant to the antiviral drug oseltamivir.
CDC continues to track this information and updated antiviral resistance figures are available in the Weekly U.S. Influenza Surveillance Report, FluView.
Has there been antiviral resistance to oseltamivir before?
Yes, laboratory surveillance during last season showed that 0.7% of H1N1 viruses isolated and studied at CDC were resistant to oseltamivir.
What does this mean?
At this time, only a small number of viruses have been tested, and it is unknown whether antiviral resistance will increase as influenza activity increases and more viruses are tested.
Is CDC recommending any changes to the current guidance on the use of antivirals for the 2007-08 influenza season?
No, CDC is not recommending any changes to the current guidance on the use of influenza antivirals. CDC and the Advisory Committee on Immunization Practices (ACIP) recommend that oseltamivir (brand name Tamiflu®) or zanamivir (brand name Relenza®) can be used for the treatment and prevention of flu in the United States this season. Although amantadine and rimantadine (two other influenza antiviral drugs) also are FDA-approved for treatment or prevention of influenza, these two drugs are NOT recommended for use in the United States during the 2007-08 flu season because many recent flu viruses are resistant to these drugs. This guidance can be found in Prevention & Control of Influenza - Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007 Jul 13;56(RR06):1-54. Also available as PDF.
CDC will continue to monitor the situation as additional information is collected.
What is CDC doing about antiviral resistance in the United States?
CDC will continue ongoing surveillance and testing of influenza viruses. Additionally, CDC is working with the state public health departments and the World Health Organization to collect additional information on oseltamivir resistance in the U.S. and worldwide. The information collected will assist in making informed public health policy recommendations.
What implications would oseltamivir resistance have for the U.S. antiviral stockpile that was created as part of the United States pandemic plan?
The U.S. antiviral drug stockpile contains both neuraminidase inhibitor agents, oseltamivir and zanamivir. These medications are to be used in the event that a novel influenza A subtype virus, such as avian influenza A (H5N1) virus, emerges and spreads easily among humans. Current pandemic antiviral drug use strategies include containment of an initial pandemic outbreak and treatment of persons with pandemic disease.
Influenza surveillance this season in the U.S has found that 10.2% of seasonal influenza A (H1N1) viruses have genetic mutations that make them resistant to oseltamivir. No resistance to zanamivir has been detected.
The stockpile is for the control of pandemic influenza, and is not for seasonal influenza use. And, resistance among seasonal strains does not predict resistance among pandemic influenza viruses.
Antiviral drugs, such as oseltamivir are one component of a multi-faceted approach to pandemic preparedness planning and response. The effectiveness of any drug during a pandemic is difficult to predict, as it is not possible to know which virus will cause the next pandemic.
Oseltamivir remains the drug recommended by the World Health Organization as the first-line influenza antiviral drug for the treatment of H5N1 patients. A very small number of patients infected with avian influenza A (H5N1) virus had evidence of oseltamivir resistance in viruses that were isolated from them, and these patients died. These H5N1 viruses did not spread to others.
CDC will continue ongoing surveillance and testing of influenza viruses for antiviral resistance among seasonal and novel influenza viruses such as H5N1 viruses.
For more information about the U.S. antiviral drug stockpile, visit PandemicFlu.gov and Antiviral Drug Distribution and Use.
- Page last modified April 11, 2008
- Content Source: Coordinating Center for Infectious Diseases (CCID)
- National Center for Immunization and Respiratory Diseases (NCIRD)
