Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients.
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.
Avery
R K
RK
Infectious Diseases, The Cleveland Clinic, Cleveland, Ohio, USA.
Marty
F M
FM
Strasfeld
L
L
Lee
I
I
Arrieta
A
A
Chou
S
S
Tatarowicz
W
W
Villano
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001562:Benzimidazoles; D015774:Ganciclovir; D012263:Ribonucleosides; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole