Vaccine and Infectious Disease Division

Case report: Development of antiviral resistance to pandemic H1N1

The 2009 pandemic H1N1 strain was dangerous to many populations, but especially to immunocompromised patients such as stem cell transplant recipients.  In such people, antiviral treatment with the drug peramivir is used in emergency situations, as it can be administered via IV, unlike the more commonly used flu antiviral, oseltamivir (also known as Tamiflu).  However, in some rare cases strains of H1N1 can arise that are resistant to both antiviral drugs.  VIDD postdoctoral fellow Dr. Christian Renaud and colleagues developed molecular techniques to quickly identify the most common antiviral-resistant H1N1 strain, which carries a specific single mutation (H275Y in the neuraminidase protein). 

Renaud and colleagues, led by VIDD member Dr. Michael Boeckh, describe a case report in which a stem cell transplant patient developed severe disease caused by H1N1 and died 28 days after being admitted to the University of Washington Medical Center hospital, as the strain was resistant to the drug treatment he received.  The scientists tested lung wash samples from the patient for presence of H1N1RNA, and for the presence of the resistance mutation once it was clear he was not responding to peramivir treatment.  While the man was on peramivir, the population of drug resistant H1N1 viruses in his system went from 0 to 100%.  Eventually, the FDA granted approval for emergency use of another antiviral drug, zanamivir.  The levels of drug-resistant H1N1 did decrease once the patient was started on zanamivir, but he had already suffered significant organ failure.  This case showed the importance of rapid testing for drug-resistant strains of H1N1, and the immediate availability of alternative treatments.

Renaud C, Pergam SA, Polyak C, Jain R, Kuypers J, Englund JA, Corey L, Boeckh MJ. Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir.  Transpl Infect Dis. 2010 Dec;12(6):513-517.