Antiviral resistance of cytomegalovirus strains is a growing problem in the transplant setting as it can concern 5% of patients with CMV replication. It is a consequence of the intensive and prolonged use of the three clinically approved inhibitors of the viral polymerase UL54, ganciclovir cidofovir and foscarnet. Resistance to ganciclovir can result from either mutations of the UL97 kinase, dispensable for its activation, which may appear within one month of therapy, or later from mutations in the UL54 viral polymerase, that can confer resistance to all antivirals. Screening for resistance is based on genotyping from clinical sample or isolates, and has to be associated whenever isolates are obtained to phenotype to evaluate the fitness of the virus and to test new drugs in the pipeline. Plasmatic dosage of the molecules, available for ganciclovir, reduction of immunosuppression, and if necessary modification of the antiviral regimen guided by genotype and/or phenotype are associated to control CMV infection in case of resistance.
Keywords: UL97 kinase; antiviral therapy; cytomegalovirus; polymerase; resistance.