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Open Access Case report

Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant recipient

Axel Schubert1, Karoline Ehlert2, Susanne Schuler-Luettmann3, Eva Gentner1, Thomas Mertens1 and Detlef Michel1*

Author Affiliations

1 Institut für Virologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany

2 Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany

3 Institut für Medizinische Mikrobiologie, Klinische Virologie, Von-Stauffenberg-Str. 36, 48151 Münster, Germany

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BMC Infectious Diseases 2013, 13:330  doi:10.1186/1471-2334-13-330

Published: 19 July 2013

Abstract

Background

Human cytomegalovirus infections are still significant causes of morbidity and mortality in transplant recipients. The use of antiviral agents is limited by toxicity and evolving resistance in immunocompromised patients with ongoing viral replication during therapy. Here, we present the first documented case of genotypic resistance against maribavir in a bone marrow transplant (BMT) recipient.

Case presentation

The female 13-year-old patient was suffering from a refractory cytopenia. Ganciclovir, foscarnet, cidofovir, leflunomide and maribavir, an inhibitor of the cytomegalovirus UL97 protein, were administered to treat a therapy-resistant cytomegalovirus infection. Viral mutations conferring resistance against nucleotide and pyrophosphate analogs as well as maribavir (MBV) have evolved sequentially. Particularly, impressive was the fast emergence of multiple mutations T409M, H411Y and H411N conferring maribavir resistance after less than 6 weeks.

Conclusion

We describe the fast emergence of cytomegalovirus variants with different maribavir resistance associated mutations in a bone marrow transplant recipient treated with MBV 400 mg p.o. twice per day. The results suggest that a high virus load permitted a selection of several but distinct therapy-resistant HCMV mutants. Since a phase II study with MBV is intended for the treatment of resistant or refractory HCMV infections in transplant recipients this has to be kept in mind in patients with high viral loads during therapy (NCT01611974).

Keywords:
Antiviral resistance; Cytomegalovirus; Maribavir; Ganciclovir; Foscarnet; Bone marrow transplantation