Influenza Antiviral Drug Resistance

Questions & Answers

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. In the United States, four antiviral drugs are FDA-approved for use against influenza: amantadine, rimantadine, zanamivir (Relenza®) and oseltamivir (Tamiflu®). The adamantane drugs (amantadine and rimantadine) are approved for influenza A, while the neuraminidase inhibitor drugs (zanamivir and oseltamivir) are approved for both influenza A and influenza B. CDC issues guidance for health care providers on which antiviral drugs to use each flu season.

How does antiviral resistance happen?

The ability to constantly change is a hallmark of influenza viruses. Flu viruses often change from one season to the next and can even change within the course of one flu season. As an influenza virus replicates (i.e., make copies of itself), the genetic makeup may change in a way that results in the virus becoming resistant to one or more of the antiviral drugs used to treat or prevent influenza. Resistance of influenza A viruses to antiviral drugs can occur spontaneously or emerge during the course of antiviral treatment or antiviral exposure.

How is antiviral resistance detected?

CDC routinely collects viruses through a domestic and global surveillance system to monitor for changes in influenza viruses. 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.

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What is CDC doing to monitor antiviral resistance in the United States?

CDC conducts ongoing surveillance and testing of influenza viruses to monitor for antiviral resistance in collaboration with state public health departments and the World Health Organization (WHO). The information collected is used in making informed public health policy recommendations about the use of influenza antiviral medications.

How does CDC improve monitoring of influenza viruses for antiviral resistance?

CDC continually improves the ability to rapidly detect and monitor antiviral resistance through improvements in laboratory methods and by increasing the number of surveillance sites domestically and globally and increasing the number of laboratories that can test for resistance. Enhanced surveillance efforts have provided CDC with the capability to detect resistant strains more quickly, and enabled CDC to monitor for changing trends over time.

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 on which antiviral drugs should be used for treating or preventing flu.

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How did influenza antiviral resistance patterns change during the 2011-2012 influenza season?

Antiviral resistance patterns did not change significantly from the previous season. Most of the influenza viruses tested during 2011-2012 continued to be susceptible to the antiviral drugs recommended for influenza by the Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) (oseltamivir and zanamivir) and H1N1 and H3N2 resistance to the adamantanes class of antiviral drugs remains widespread.

Specifically, for the 2012-2012 season:

• 98.6% of the tested 2009 H1N1 viruses were susceptible to oseltimivir (Tamiflu®), and 100% of the 2009 H1N1 viruses tested were susceptible to zanamivir (Relenza®).
• 100% of influenza A (H3N2) tested were susceptible to both oseltamivir and zanamivir, and;
• 100% of influenza B viruses tested were susceptible to both oseltamivir and zanamivir.
• The 2009 H1N1 and the H3N2 viruses showed high levels of resistance to amantadine and rimantadine.

Because there were no dramatic changes in antiviral resistance patters during 2011-2012, the 2012-2013 guidance on the use of influenza antiviral drugs remains the same.

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What antiviral drugs are recommended for use during the 2012-2013 flu season?

Antiviral medications currently recommended include oseltamivir (Tamiflu®) and zanamivir (Relenza®), based upon viral surveillance and resistance data from the 2011-2012 influenza season summary. These data indicate that of the vast majority of currently circulating influenza virus strains are sensitive to these medications. Rare exceptions were detected during 2011-2012.

From January to April, 2012, 16 oseltamivir-resistant 2009 H1N1 viruses were detected. Three patients were using oseltamivir for 1 day or more at the time of specimen collection. Thirteen had no exposure to oseltamivir; out of those 13 patients, 2 had family members using oseltamivir.

Eleven of the 16 oseltamivir-resistant viruses were collected from January to April 2012 and were from Texas, where a total of 419 2009 H1N1 specimens were tested for oseltamivir resistance. Oseltamivir resistance remained quite low nationally and in Texas, even though the percentage of oseltamivir-resistant 2009 H1N1 viruses in Texas (2.6%) was higher than the national percentage. Updates on antiviral resistance surveillance are available for clinicians at the Weekly U.S. Influenza Surveillance Report (FluView).

What implications does antiviral resistance have for the U.S. antiviral stockpile that was created as part of the United States pandemic plan?

Antiviral drugs are one component of a multi-faceted approach to pandemic preparedness planning and response. Oseltamivir is the drug recommended by the World Health Organization (WHO) as the first-line influenza antiviral drug for the treatment of patients infected with influenza A (H5N1). The U.S. influenza antiviral drug stockpile includes supplies of both of the neuraminidase inhibitor agents, oseltamivir and zanamivir. These medications are to be used in the event that a novel influenza A subtype virus, such as the avian influenza A (H5N1) virus, emerges and spreads easily among humans. During the 2009-2010 H1N1 pandemic, antiviral drugs were released from the stockpile and used to treat infection with the 2009 (H1N1) influenza A virus. Information about how antiviral drugs from the stockpile were used during the 2009 H1N1 pandemic is available at The 2009 H1N1 Pandemic: Summary Highlights, April 2009-April 2010. The stockpile is for use during an influenza pandemic, not for treatment of seasonal influenza. Resistance among seasonal viruses does not predict resistance among pandemic influenza viruses.

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 Antiviral Drug Distribution and Use [272 KB, 19 pages].

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