title: Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France.
abstract: The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance.
authors.affiliation: Laboratoire de Virologie, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France; Virologie et Pathologie Humaine, Université Lyon 1, EA 4610, Faculté de Médecine RTH Laënnec, Lyon, France. Electronic address: emilie.frobert@chu-lyon.fr.
authors.forename: Emilie
authors.initials: E
authors.lastname: Frobert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Paris, France; AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière - Charles Foix, Service de Virologie, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Burrel
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ducastelle-Lepretre
authors.affiliation: Laboratoire de Virologie, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Billaud
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
authors.affiliation: Laboratoire de Virologie, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France; Virologie et Pathologie Humaine, Université Lyon 1, EA 4610, Faculté de Médecine RTH Laënnec, Lyon, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Casalegno
authors.affiliation: Laboratoire de Virologie, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Nave
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Paris, France; AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière - Charles Foix, Service de Virologie, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Boutolleau
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud, Lyon, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Laboratoire de Virologie, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France; Virologie et Pathologie Humaine, Université Lyon 1, EA 4610, Faculté de Médecine RTH Laënnec, Lyon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lina
authors.affiliation: Laboratoire de Virologie, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France; Virologie et Pathologie Humaine, Université Lyon 1, EA 4610, Faculté de Médecine RTH Laënnec, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Morfin
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D005602:France / Q000453:epidemiology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D000212:Acyclovir
keywords: Antiviral drug resistance; Hematopoietic stem cell transplant patients; Herpes simplex virus; Survey; UL23 thymidine kinase; UL30 DNA polymerase