Dynamics of coexisting HCMV-UL97 and UL54 drug-resistance associated mutations in patients after haematopoietic cell transplantation
| Autor: | Klaus Hamprecht, Dana G. Wolf, Gerhard Jahn, Elfriede Mikeler, Matthias Vöhringer, Christoph Faul, Katharina Göhring, Wichard Vogel, Wolfgang Bethge |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Ganciclovir Foscarnet viruses medicine.medical_treatment Cytomegalovirus DNA-Directed DNA Polymerase Drug resistance Hematopoietic stem cell transplantation Biology Antiviral Agents Viral Proteins chemistry.chemical_compound Fatal Outcome Virology Drug Resistance Viral medicine Humans Retrospective Studies Hematopoietic Stem Cell Transplantation Middle Aged Viral Load Multiple drug resistance Phosphotransferases (Alcohol Group Acceptor) Phenotype Infectious Diseases chemistry Cytomegalovirus Infections Mutation Immunology Restriction fragment length polymorphism Viral load Polymorphism Restriction Fragment Length medicine.drug Cidofovir |
| Zdroj: | Journal of Clinical Virology. 57:43-49 |
| ISSN: | 1386-6532 |
| Popis: | Background Resistance to antiviral drugs can be a severe problem in transplant recipients. Mutations in the HCMV phosphotransferase-gene (UL97) and the polymerase-gene (UL54) are responsible for resistance against ganciclovir (GCV), cidofovir (CDV) and foscarnet (PFA). Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against PFA and CDV is associated to mutations in the UL54-gene. There are only few reports about multidrug-resistance with mutations in both genes in patients after allogeneic haematopoietic cell transplantation (HCT). Objectives To asses retrospectively the role of UL97/UL54-mutations for clinical deterioration. Study design We present here three patients after HCT developing multidrug-resistance with coexisting UL97 and UL54-mutations. Genotypical resistance screening was done with restriction-fragment-length-polymorphism (RFLP), sequencing of UL97/UL54, and LightCycler real-time PCR. Phenotyipcal testing was performed by a cell-associated plaque-reduction-assay. Plasma viral-load (VL) was determined longitudinally using Roche Cobas-Amplicor-System (Roche Diagnostics). In one case VL was also correlated to different ratios of coexisting UL97-wildtype and mutant variants. Results All three patients developed multidrug resistant HCMV-infections with one or more UL97 and UL54-mutation detected by RFLP, sequencing and LightCycler-analysis. Two out of three patients showed biphasic VL kinetics with manifestation of UL97 drug-resistance prior/or at peak VL. UL54-mutations emerged also in all three patients either at increasing VL levels of ≥10 5 copies/ml or at peak VL. Conclusions The development of coexisting HCMV UL97 and UL54-mutations conferring drug-resistance after HCT is not strictly associated with fatal outcome in one of our three patients. Manifestation of drug resistant combined UL97/UL54-mutations occurred prior to a second VL peak under (V)GCV/PFA co-treatment. |
| Databáze: | OpenAIRE |
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