In recent years, the treatment of HCMV disease and clinical outcome has been enormously improved by monitoring active sys-temic infections and the introduction of HCMV antiviral therapy.
Nevertheless, the situation concerning HCMV treatment is complex and still not satisfying. Taken the current knowledge into account, it can be assumed that many factors contribute to the overall drug susceptibility phenotype of a patient’s virus population. Among those are the underlying disease, the degree of immunosupression, the clinical sample, the type and position of mutations in UL97 and UL54, the viral replicative fitness, and finally – depending on the replicative fitness – the dynamics of a resistant virus population.
The questions of the treating clinician are clearly defined: (i) who has to be treated, (ii) when to start, (iii) which antiviral drug to use, (iv) when to augment the dosage or switch the drug due to virological susceptibility findings?
Since phenotypical testing of isolated viruses is not practicable in the clinics, genotyping is the method of choice because results can be obtained reliably within hours. Still, all individual mutations in the genes relevant for resistance have to be characterised phe-notypically, including combinations of these mutations. Our new web-based search tool and database will be a major improvement for the fast evaluation of sequence data regarding their suscepti-bility phenotype. Finally, reduced drug susceptisuscepti-bility – virological resistance – has to be correlated with therapy failure – clinical resistance – and patient’s outcome in prospective clinical studies.
Acknowledgements
We would like to thank Johann M Kraus and Ludwig Lausser for technical support and Bernd Ehlers for the information on detection of HCMV subpopulations by pyrosequencing. Meike Chevillotte is participant in the International Graduate School in Molecular Medicine Ulm, funded by the Excellence Initiative of the Ger-man federal and state governments. University Hospital Ulm and the Robert-Koch-Institut, Berlin (Netzwerk für Infektionen bei Immundefizienz oder Schwangerschaft), supported the work of Meike Chevillotte. The German Academic Exchange Service (DAAD) supported the work of Feng-Mao Lin and this research was partly funded by a “Forschungsdozent” grant through the “Stifterverband für die Deutsche Wissenschaft” and by the German Science Foun-dation (SFB 518, Project C05) to Hans A. Kestler.
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