Influenza Virus Resistance to Antiviral Agents: A Plea for Rational Use

TLDR

Influenza vaccination can prevent infection, but treatment options are limited to antiviral agents, many strains are resistant to adamantanes and even neuraminidase inhibitors, and monotherapy historically drives resistance. We argue that combination antiviral therapy, updated treatment guidelines, point‑of‑care diagnostics, and universal vaccination are essential to protect the population and preserve antiviral efficacy. CDC data show that a high proportion of circulating H1N1, influenza B, and H5N1 viruses are oseltamivir‑resistant, demonstrating that monotherapy is irrational and may accelerate resistance.

Abstract

Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. At the current time, nearly all influenza A/H3N2 viruses and a percentage of influenza A/H1N1 viruses are adamantane resistant, which leaves only neuraminidase inhibitors available for treatment of infection with these viruses. In December 2008, the Centers for Disease Control and Prevention released new data demonstrating that a high percentage of circulating influenza A/H1N1 viruses are now resistant to oseltamivir. In addition, oseltamivir-resistant influenza B and A/H5N1 viruses have been identified. Thus, use of monotherapy for influenza virus infection is irrational and may contribute to mutational pressure for further selection of antiviral-resistant strains. History has demonstrated that monotherapy for influenza virus infection leads to resistance, resulting in the use of a new monotherapy agent followed by resistance to that new agent and thus resulting in a background of viruses resistant to both drugs. We argue that combination antiviral therapy, new guidelines for indications for treatment, point-of-care diagnostic testing, and a universal influenza vaccination recommendation are critical to protecting the population against influenza virus and to preserving the benefits of antiviral agents.