Tamiflu (oseltamivir) has been stockpiled by many countries anxious to be prepared should a flu pandemic strike, but the problem according to an international team of researchers, is that influenza viruses can become resistant to antiviral drugs, and the widespread use of a single drug is likely to increase the risk that a resistant strain will emerge.
The concern is that if such a strain were to spread widely, the effectiveness of antiviral drugs such as Tamiflu in treating infected patients, as well as their ability to slow the spread of a pandemic, would be greatly reduced.
The international research team, led by Joseph Wu of the University of Hong Kong, included scientists from the UK and the U.S. who used a mathematical model to represent the global spread of an influenza pandemic.
The team found that treating just the first 1% of the population in a local epidemic with a secondary drug, rather than with oseltamivir, could substantially delay the development of resistance to oseltamivir and this reduction in resistance was predicted to benefit not only local populations, but also those in distant parts of the world where the pandemic would subsequently spread through air travel.
The team say in the current emerging swine flu situation, the secondary drug could be Relenza (zanamivir), the only other approved drug to which the new H1N1 strain has been found to be susceptible.
This strategy say the researchers could be as effective because it delays use of the primary stockpiled drug until a certain proportion of the local population (about 1.5% according to the model) has been infected with virus that remains susceptible to the primary drug - with drug-sensitive virus in the majority as people recover from infection and develop immunity, only a minority of further infections are likely to be resistant to the primary drug.
The researchers say technically, such a delay could be achieved by postponing the launch of any antiviral intervention, but because even a short delay would mean denying antiviral drugs to people who would benefit from them, the researchers instead propose the deployment of a small stockpile of a secondary antiviral during the early phase of the local epidemic.
The model was prepared before the current swine flu crisis, and considered two possible strategies, "early combination chemotherapy" (treatment with two drugs together while both are available, assuming that clinical trials show such a combination to be safe for patients) and "sequential multi-drug chemotherapy" (treatment with the secondary drug until its stockpile is exhausted, then treatment with the primary drug).
The researchers say while either strategy could be effective in principle, only the sequential strategy would be practical in responding to the currently emerging H1N1 swine flu, because the safety of combining zanamivir with oseltamivir (for combination therapy) is not established.
After simulating the impact of these strategies in a single population, the researchers then introduced international travel data into their model to investigate whether these two strategies could limit the development of antiviral resistance at a global scale.
They say this analysis predicted that, provided the population that was the main source of resistant strains used one of the strategies, both strategies in distant, subsequently affected populations would be able to reduce the consequences of resistance, even if some intermediate populations failed to control resistance.
The research is published in PLoS Medicine.