Oseltamivir-zanamivir bitherapy compared to oseltamivir monotherapy in the treatment of pandemic 2009 influenza A(H1N1) virus infections.

The emergence of oseltamivir resistance in 2007 highlighted the need for alternative strategies against influenza. To limit the putative emergence of resistant viruses this clinical trial aimed to evaluate the antiviral efficacy and tolerability of oseltamivir-zanamivir (O+Z) bitherapy compared to oseltamivir monotherapy (O). This clinical trial was designed in 2008-2009 and was conducted during the A(H1N1) influenza virus pandemic in 2009-2010. The A(H1N1)pdm09 viruses were reported to be sensitive to oseltamivir and zanamivir but resistant to amantadine.During the pandemic phase in France, adults with influenza-like illness for less than 42h and who tested positive to influenza A were randomised into treatment groups: (O+Z) or (O). Patients had a nasal wash at day 0, before the beginning of treatment and daily at days 1 to 4. They also had a nasal swab at days 5 and 7 to check for the negativation of viral excretion. Virological response was assessed using the GAPDH adjusted M gene quantification.Analysis was possible for 24 patients, 12 in the (O+Z) arm and 12 in the (O) arm. The mean viral load decreased at around 1 log(10)cgeq/μl per day regardless of allocated treatment group. We could not detect any significant difference between treatment groups in the duration needed to alleviate symptoms. All treatments were well tolerated. No oseltamivir-resistant H275Y NA mutated virus has been detected in patients of both treatment groups.The sample size of our study is too limited to be fully informative and we could not detect whether combination therapy (O+Z) improves or reduces the effectiveness of oseltamivir in the treatment of influenza A(H1N1)pdm09 virus infection in community patients. Additional studies are needed to improve the antiviral treatment of patients infected with influenza virus.