WHAT CLINICIANS NEED TO KNOW ABOUT ANTIVIRAL DRUGS AND VIRAL RESISTANCE

During the last decade, significant advances have been made in the development and use of antiviral agents for the successful treatment of a number of viral infections.8, 51, 57 An expanding array of antiviral drugs are currently available for the management of infections caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV), influenza A virus, respiratory syncytial virus (RSV), human immunodeficiency virus type 1 (HIV-1), papillomaviruses, and hepatitis B and C viruses. The increased number and use of antiviral agents, however, has led to the emergence of drug-resistant viruses, particularly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or hematologic malignancy or those who have undergone organ transplantation. For comprehensive reviews on specific viruses, see references 26, 41, 64, 81–83, and 102. Clinical situations that favor the development of resistance include long-term suppressive therapy, recurrent intermittent therapy, and the use of less than optimum doses of an antiviral agent. Generally, the emergence and isolation of drug-resistant viruses is associated more so with the therapeutic use of antiviral agents and does not seem to be caused by prophylactic treatment. As more patients fail to respond to appropriate therapy and additional antiviral agents are produced, it will also become important for diagnostic virology laboratories to provide rapid and practical antiviral susceptibility testing to assist physicians in defining drug resistance and choosing appropriate alternative therapies. This review describes the major antiviral agents, their mechanisms of action, and the development of drug resistance following antiviral therapy. A brief overview of the available phenotypic and genotypic susceptibility assays for detecting antiviral resistance is also discussed.