Antiviral Drugs for the Treatment and Prevention of Influenza

Abstract

This paper provides an overview of the currently available treatment options for influenza infections. Currently, the options are limited to only one class of drugs known as the neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir and peramivir) as there is widespread resistance against the adamantanes, an older class of antivirals. This review therefore discusses the mode of action, dosing, summary of clinical trial data and resistance within the context of NAIs. Newer antiviral therapies in late-phase clinical trials are also summarized in this review. Oseltamivir is the most commonly used NAI amongst the four different types available. The most recent meta-analysis of placebo-controlled trials demonstrates that for uncomplicated seasonal influenza, oseltamivir reduces symptoms by 16–24 h, while observational studies cumulatively suggest that oseltamivir treatment reduces mortality in severely ill patients. NAIs also play an important role in the treatment and control of avian influenza infections in humans, which is a public health concern due to their high case fatality rate. The latest analysis of data suggests that early treatment with oseltamivir can be attributed to reducing mortality in patients with avian A(H5N1) infections; data regarding oseltamivir effectiveness against A(H7N9) infections is however more limited. During the 2014–2015 influenza season, the frequency of resistance to the NAIs in all circulating viruses was below 1%, but immunocompromised patients infected with influenza are often at higher risk of shedding resistant viruses due to slow viral clearance and extended treatment regimens. Favipiravir, a polymerase inhibitor, has received limited approval for use in Japan, but its use is restricted to novel viruses that are resistant to other antiviral therapies. Antivirals such as thiazolide, nitazoxanide and endonuclease inhibitor, S-033188, are currently in phase III clinical trials and other influenza antivirals are in early or mid-phase clinical trials. This review highlights a lack of different treatment options for influenza infections. While there are four different types of NAIs, in many countries, oseltamivir is the only available option. New therapies are being rapidly developed to meet the need for a greater variety of antivirals, and as such, it is likely that over the next decade, a broader range of influenza therapeutics will become available for treatment.