Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives

Abstract

Influenza is a major cause of substantial morbidity and mortality in humans every year. Vaccination is the main strategy to prevent influenza infection, but antiviral agents also play an important role in the control of both seasonal and pandemic influenza. During the influenza A/H1N1 pandemic in 2009, early prompt antiviral therapy may have reduced the severity of the influenza outcomes including pneumonia, hospitalization and mortality in the Republic of Korea. Since the 2009 H1N1 pandemic, there have been increasing usages of antiviral agents for the treatment of patients with seasonal influenza. Although currently rare, antiviral resistance among influenza viruses may emerge and increase with increased use of neuraminidase inhibitors. New agents with different modes of action are under investigation, including favipiravir, DAS181, nitazoxanide and broad-spectrum neutralizing monoclonal antibodies. Data are limited with respect to high-dose and combination antiviral therapies. So, clinical trials are warranted to evaluate diverse antiviral combinations that may be synergistic and less likely to induce breakthrough resistance.

Keywords:

• antiviral agents
• drug resistance
• epidemics
• influenza
• Republic of Korea

Financial & competing interests disclosure

This study was supported by a grant from the Korea Healthcare Technology R&D Project of the Ministry of Health & Welfare of the Republic of Korea (No. A103001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Key issues

• Annually, 10–20% of the general population is affected by seasonal influenza.

• Influenza is responsible for approximately 3–5 million severe cases and 25,000–50,000 deaths worldwide in epidemic years.

• During the 2009 influenza pandemic, inpatient and outpatient visits increased 15–20-fold and 10-fold, respectively, compared with the two previous seasons.

• Antiviral agents contributed to mitigate the impact of the 2009 influenza A/H1N1 pandemic.

• A standard dose of oseltamivir is recommended for the treatment of severe influenza.

• Reimbursement for antiviral usage needs to be expanded to cover patients with neurological disorders or morbid obesity.

• Reimbursement for antiviral usage needs to be expanded to cover patients with influenza before the epidemic alert is announced during influenza seasons.

• Emergence of antiviral resistance during monotherapy would be a drawback to the treatment of severe influenza. Antiviral resistance may emerge and increase with incremental use of neuraminidase inhibitors.

• Antiviral combination therapy is not generally recommended for the treatment of severe influenza; however, antiviral combinations with different modes of actions might be beneficial in the treatment of chronically ill patients with severe influenza infections, preventing the emergence of antiviral resistance.

• Development of human monoclonal antibodies would provide new perspectives on the treatment of severe and drug-resistant influenza virus infections, giving advanced insights toward a universal influenza vaccine.

Notes