title: Clinical and virologic characterization of acyclovir-resistant varicella-zoster viruses isolated from 11 patients with acquired immunodeficiency syndrome.
abstract: We studied the clinical resistance to acyclovir of infections with varicella-zoster viruses (VZV) in patients with acquired immunodeficiency syndrome, and we correlated it to virologic analyses. Eleven patients with VZV infections (treated with acyclovir, 30 mg/kg/day, given intravenously, or 4 g/day, given orally) were included in the study because of the failure of 10 days of acyclovir therapy. Susceptibility of VZV isolates to acyclovir was tested using a plaque reduction assay to determine the 50% inhibitory concentration (IC(50)) of acyclovir and the SI(50) (IC(50) of the patient isolate/IC(50) of the reference strain) to acyclovir. The thymidine kinase (TK) gene, which supports the resistance, was sequenced on amplified products. Only 3 patients had a significant increase in the IC(50), as compared with the IC(50) of the reference strain (SI(50) of > or =4), and a mutation in the TK gene. For the other 8 patients, the clinical resistance was not confirmed by the virologic results: the SI(50) was < 4, and no mutation was detected in the TK gene. Because no acyclovir-resistant strain appeared during a shorter period of time, we suggest an increase in the duration of the treatment to 21 days before acyclovir resistance is suspected.
authors.affiliation: Department of Virology, La Pitie-Salpêtrière Hospital (Assistance Publique-Hôpitaux de Paris), 75651 Paris Cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: Saint-Léger
authors.forename: E
authors.initials: E
authors.lastname: Caumes
authors.forename: G
authors.initials: G
authors.lastname: Breton
authors.forename: D
authors.initials: D
authors.lastname: Douard
authors.forename: P
authors.initials: P
authors.lastname: Saiag
authors.forename: J M
authors.initials: JM
authors.lastname: Huraux
authors.forename: F
authors.initials: F
authors.lastname: Bricaire
authors.forename: H
authors.initials: H
authors.lastname: Agut
authors.forename: A M
authors.initials: AM
authors.lastname: Fillet
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000821:virology*; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir