Antiviral therapy: current options and challenges

This article reviews current options and concepts for drug treatment of viral infections with the exception of human immunodeficiency virus infection. Advances in antiviral drug development and in rapid diagnostic methods have resulted in efficient management strategies, particularly for infections due to herpes simplex virus, varicella-zoster virus, cytomegalovirus, influenza A and B viruses, and chronic hepatitis B and C. Newer antiviral agents, such as valaciclovir and famciclovir, have a high oral bioavailability which permits less frequent intake and avoidance of intravenous therapy in many cases. As an alternative to subcutaneous interferon-alpha (IFN-alpha) treatment, oral lamivudine is now approved for therapy of chronic hepatitis B. The addition of oral ribavirin to IFN-alpha treatment has been shown to be superior to IFN-alpha alone for therapy of chronic hepatitis C. By contrast to amantadine, neuraminidase inhibitors such as zanamivir or oseltamivir (GS4104) have activity against both influenza A and B viruses and are well tolerated. First results of controlled trials with these agents are discussed. The emergence of herpes virus resistance to antiviral drugs is of concern, and validation of alternative treatment for patients with documented resistance is required. Future investigations may also help to clarify the therapeutic role of novel antiviral drugs and formulations, such as the oral prodrug of cidofovir, valganciclovir, compounds 1263W94 and Bay 38-4766, and pleconaril.