Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients

R. K. Avery, F. M. Marty, Lynne Strasfeld, I. Lee, A. Arrieta, Sunwen Chou, W. Tatarowicz, S. Villano

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Background: Despite advances in cytomegalovirus (CMV) prophylaxis and therapy, some transplant recipients still develop refractory CMV infections. Maribavir (MBV), an investigational benzimidazole antiviral agent, acts by a mechanism different from that of existing anti-CMV drugs. Previous Phase I and II studies have demonstrated a favorable safety profile for MBV, but its utility in treatment of complex CMV syndromes is unknown.Methods. Between June and December 2008, MBV was released for use under individual emergency investigational new drug applications requested by treating physicians and approved by the US Food and Drug Administration and local institutional review boards. Six patients (5 solid organ transplant recipients and 1 hematopoietic stem cell transplant recipient) who had failed to respond to other therapies and/or had known ganciclovir-resistant CMV were treated with MBV at a starting oral dose of 400 mg twice daily. Results: Patients were treated for a median of 207 days (range, 15-376). Four of 6 patients had no detectable CMV DNAemia within 6 weeks of starting MBV therapy. One patient, who had an initial viral load of 1.8 million copies/mL, developed MBV resistance mutations. One patient, who had low serum levels of MBV, had persistent CMV DNAemia and viruria without developing genotypic or phenotypic resistance to MBV. One patient cleared CMV DNAemia, but died of pneumonia and multiorgan failure. No significant adverse effects attributable to MBV were observed.Conclusions. MBV deserves further systematic evaluation as treatment for CMV infection that is resistant and/or refractory to standard therapies, but its optimal dose, duration of therapy, and use in combinations versus as a single agent have yet to be determined.

Original languageEnglish (US)
Pages (from-to)489-496
Number of pages8
JournalTransplant Infectious Disease
Volume12
Issue number6
DOIs
StatePublished - Dec 2010

Fingerprint

Cytomegalovirus Infections
Cytomegalovirus
Therapeutics
Investigational New Drug Application
maribavir
Transplant Recipients
Transplants
Ganciclovir
Research Ethics Committees
United States Food and Drug Administration
Hematopoietic Stem Cells
Viral Load
Antiviral Agents
Pneumonia
Emergencies
Physicians
Safety
Mutation

Keywords

  • Antiviral resistance
  • Cytomegalovirus
  • Ganciclovir
  • Maribavir

ASJC Scopus subject areas

  • Transplantation
  • Infectious Diseases

Cite this

Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. / Avery, R. K.; Marty, F. M.; Strasfeld, Lynne; Lee, I.; Arrieta, A.; Chou, Sunwen; Tatarowicz, W.; Villano, S.

In: Transplant Infectious Disease, Vol. 12, No. 6, 12.2010, p. 489-496.

Research output: Contribution to journalArticle

Avery, R. K. ; Marty, F. M. ; Strasfeld, Lynne ; Lee, I. ; Arrieta, A. ; Chou, Sunwen ; Tatarowicz, W. ; Villano, S. / Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. In: Transplant Infectious Disease. 2010 ; Vol. 12, No. 6. pp. 489-496.
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