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Questions & Answers
Influenza Antiviral Drug Resistance
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 2008-09 influenza season because many 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 2008-09 season. Monitoring is continuing for resistance to the adamantane drugs to see if the proportion of flu viruses that are resistant is changing.
What did we see during the 2007-2008 season in terms of antiviral resistance monitoring or surveillance in the United States?
During the 2007-08 flu season, a small increase in the overall number of flu viruses resistant to the neuraminidase inhibitor oseltamivir was observed. Among specimens collected since October 1, 2007, no resistance to oseltamivir was identified among the 444 influenza A (H3N2) or the 305 influenza B viruses tested. However, 111 (10.9%) of the 1,020 influenza A (H1N1) viruses tested were found to be resistant to oseltamivir, an increase from four (0.7%) of 588 influenza A (H1N1) viruses tested during the 2006-07 season. No resistance to zanamivir has been detected.
CDC laboratory surveillance has indicated continued high resistance among influenza virus isolates to the adamantanes (amantadine and rimantadine) in the United States. Among specimens collected since October 1, 2007, 99.8% of influenza A (H3N2) viruses tested were resistant to the adamantanes. Adamantane resistance among influenza A (H1N1) viruses has been detected at a lower level with 10.8% of influenza A (H1N1) viruses resistant to adamantanes. Adamantanes are not used for influenza B virus infections.
What is CDC doing to monitor 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 during the 2007-08 season in the U.S found that 10.9% of seasonal influenza A (H1N1) viruses have genetic mutations that make them resistant to oseltamivir. No resistance to oseltamivir was detected among influenza A(H3N2) or influenza B viruses. 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 patients infected with influenza A(H5N1). 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. These influenza A (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 July 17, 2008
- Content Source: Coordinating Center for Infectious Diseases (CCID)
- National Center for Immunization and Respiratory Diseases (NCIRD)
