title: Antiviral drug resistance in herpesviruses other than cytomegalovirus.
abstract: The discovery of acyclovir (ACV), a nucleoside analogue, more than 30 years ago, represents a milestone in the management of HSV and VZV infections. The modest activity of ACV against CMV prompted the development of another nucleoside analogue, ganciclovir, for the management of systemic and organ-specific CMV diseases. Second-line agents such as the pyrophosphate analogue foscarnet and the nucleotide analogue cidofovir have been approved subsequently. In contrast to ACV and ganciclovir, the latter drugs do not require selective phosphorylation by viral protein kinases to be converted into their active forms. Since the introduction of these antivirals, the emergence of drug-resistant mutants has been constantly reported particularly in severely immunocompromised patients such as bone marrow and solid organ transplant recipients as well as HIV-infected individuals. In this manuscript, we discuss the characteristics of the antiviral agents currently approved for the management of HSV, VZV and CMV diseases. In recent years, the resistance of CMV to antiviral drugs has been extensively reviewed. The emergence of antiviral drug resistance is also observed with other members of the Herpesviridae family, namely HSV-1, HSV-2, VZV and HHV-6, which are the focus of this review. More specifically, we describe the laboratory methods for assessing drug susceptibilities, the frequency and clinical significance of drug-resistant infections and their management.
authors.affiliation: Research Center in Infectious Diseases, Laval University, Quebec City, QC, Canada.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Piret
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D017245:Foscarnet / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015654:Herpesvirus 6, Human / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host; D063065:Organophosphonates / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D017245:Foscarnet; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir; D000212:Acyclovir