Antiviral resistance and the control of pandemic influenza

Stockpiling large amounts of oseltamivir (Tamiflu) and related antiviral drugs with the intent to treat a large fraction of the population is a key part of pandemic preparedness of many countries.

However, it is known that influenza viruses can develop resistance to these drugs. New research by Marc Lipsitch and colleagues (Harvard University) suggests that wide-spread use of antiviral drugs during a pandemic carries a substantial risk of resistance emerging and resistant influenza strains causing illness in a substantial number of people. This would counteract the benefits of antiviral drugs but is not likely to eliminate those benefits entirely.

These researchers set up a mathematical model to mimic the spread of influenza. They then fed a set of assumptions into the computer. These included information about the rate of transmission of influenza from one person to another; what proportion of people would receive antiviral drugs for prophylaxis or treatment; how likely the drugs would be to successfully treat or prevent infection; and in what proportion of people the virus might become resistant to drugs.

The modeling led to three main predictions. First, it predicted that widespread use of antiviral drugs such as oseltamivir would quickly lead to the spread of resistant viruses, even if resistant strains emerged only rarely. Second, even with resistant strains circulating, prophylaxis and treatment with oseltamivir would still delay the onset of the pandemic and reduce its total size. Third, non-drug interventions (such as social isolation and school closures) would further reduce the number of cases, but a higher proportion of cases would be caused by resistant strains if these control measures were used.