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Surveillance of herpes simplex virus resistance to antivirals: a 4-year survey.
- Source :
-
Antiviral research [Antiviral Res] 2013 Nov; Vol. 100 (2), pp. 365-72. Date of Electronic Publication: 2013 Sep 25. - Publication Year :
- 2013
-
Abstract
- Herpes simplex virus (HSV) resistance to antivirals constitutes a therapeutic challenge, especially among immunocompromised patients. This observational survey on HSV resistance to antivirals was conducted retrospectively over a 4-year period (2008-2012). A total of 211 HSV-positive clinical samples (94 HSV-1 and 117 HSV-2) recovered from 139 patients (11 immunocompetent patients, 85 immunocompromised patients, and 43 patients with unknown immune status) with suspected HSV drug-resistance were analyzed for acyclovir and foscarnet susceptibility. Antiviral resistance testing consisted in a two-step procedure including a first-step genotypic assay, based on UL23 (thymidine kinase, TK) and UL30 (Pol) gene sequencing, and a second-step phenotypic assay (i.e., plaque reduction assay) performed when unpreviously described mutations were detected. As a whole, susceptibility and resistance to antivirals were evidenced for 58 (30.7%) and 86 (45.5%) HSV, respectively, whereas antiviral profile remained undetermined for 45 (23.8%) HSV. The prevalence of drug resistance was significantly higher among HSV-2 isolates than among HSV-1 isolates (53.8% vs. 34.9%; p=0.012). The majority (i.e., 79.7%) of cases of ACV resistance conferred by TK mutations resulted from UL23 gene frameshift reading. Apart from the changes surely related to natural polymorphism or drug-resistance, 91 unpreviously reported mutations were identified in TK and Pol, including 51 potential natural polymorphisms, 22 mutations likely conferring resistance to antivirals, and 18 mutations of unclear significance.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Acyclovir pharmacology
Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Epidemiological Monitoring
Female
Genotype
Herpes Simplex epidemiology
Herpesvirus 1, Human genetics
Herpesvirus 1, Human isolation & purification
Herpesvirus 2, Human genetics
Herpesvirus 2, Human isolation & purification
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Prevalence
Retrospective Studies
Viral Proteins genetics
Young Adult
Antiviral Agents pharmacology
Drug Resistance, Viral
Foscarnet pharmacology
Herpes Simplex virology
Herpesvirus 1, Human drug effects
Herpesvirus 2, Human drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 100
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 24075863
- Full Text :
- https://doi.org/10.1016/j.antiviral.2013.09.012