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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. The adamantane drugs are approved for influenza A while the neuraminidase inhibitor drugs zanamivir and oseltamivir are approved for influenza A and influenza B. On December 19, 2008 CDC issued interim guidance for health care providers on which antiviral drugs to use during the 2008-09 flu season.
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?
Enhanced surveillance efforts have provided CDC with the capability to detect resistant strains more quickly, and enabled CDC to monitor for changing trends overtime. Virus surveillance information is helpful in making recommendations for how to treat or prevent flu.
How did influenza antiviral resistance patterns change during the 2007-08 influenza season?
During the 2007-08 influenza season, the CDC influenza laboratory and other influenza laboratories around the world showed a significant increase in the prevalence of resistance to oseltamivir among A (H1N1) viruses. In the U.S, about 13% of H1N1 viruses were found to be resistant to oseltamivir, whereas prior to 2007-08, less than 1% of viruses were resistant.
Additionally, laboratory surveillance indicated continued high resistance to the adamantanes (amantadine and rimantadine) among influenza A (H3N2) influenza viruses in the United States and about 11% among influenza A (H1N1) viruses.
What have we seen so far during the 2008-2009 season in terms of antiviral resistance monitoring in the United States?
As a result of low U.S. flu activity, few viruses have been available to CDC for antiviral resistance testing thus far. However, among viruses tested this season, a high proportion of the few influenza A (H1N1) viruses analyzed by CDC have been resistant to oseltamivir (Tamiflu®).
CDC continues to track this information and updated antiviral resistance figures are published in the “FluView” Weekly U.S. Influenza Surveillance Report.
Is CDC recommending any changes to the current guidance on the use of antivirals for the 2008-09 influenza season?
Recommendations regarding the use of antiviral medications have been reviewed given
- surveillance data that indicates all influenza A (H3N2) and influenza B viruses remain susceptible to oseltamivir;
- an increase in the number of, and geographic spread of, oseltamivir-resistance influenza A (H1N1) viruses in the United States has been detected;
- all influenza A (H1N1), H3N2, and influenza B viruses remain susceptible to zanamivir; and
- the high levels of resistance to amantadine and rimantadine among H3N2 viruses.
Different options for antiviral treatment in the setting of increased circulation of oseltamivir-resistant H1N1 viruses have been considered. These options, such as dual therapy with oseltamivir and rimantadine or use of zanamivir, were outlined in the 2008 influenza recommendations and can be found on the CDC website at http://www.cdc.gov/flu/professionals/antivirals/resistance.htm
On December 19, 2008 CDC issued interim guidance on the use of influenza antiviral medications in the United States for the 2008-09 season which is based on the 2008 ACIP recommendations.
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 does antiviral 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.
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 December 19, 2008
- Content Source: Coordinating Center for Infectious Diseases (CCID)
- National Center for Immunization and Respiratory Diseases (NCIRD)
