Phenotypic and Genotypic Testing of HSV-1 and HSV-2 Resistance to Antivirals

Resistance testing of antivirals to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can be done by phenotypic and genotypic methods. The determination of a resistant phenotype is based on the calculation of inhibitory concentrations for the antiviral drug, which should be tested. The main advantage of this resistance test is a clear interpretation of laboratory findings, but the method is time-consuming and a considerable experience is required by handling infectious virus. Genotypic resistance testing is based on the detection of resistance-related mutations in viral genes encoding the thymidine kinase and DNA polymerase, which need to be amplified and sequenced. This approach has the advantage of being faster, but only frameshift mutations, stops of translation, and amino acid substitutions described in the literature can be interpreted without doubt. By contrast, numerous novel amino acid substitutions are diagnostically less conclusive.