title: Maribavir use in practice for cytomegalovirus infection in French transplantation centers.
abstract: Maribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses. They had developed clinical (12/12) and/or virological (11/12) resistance to CMV infection. Based on a decrease of viral load in blood >1.5 log copies/mL half of them responded to MBV treatment. The individual changes varied from a rapid decrease in viral load (n = 4) to no response (n = 3) with some late response slowly decreasing viremia (n = 3). In 2 cases MBV was used as secondary prophylaxis. No clear parameter emerged as a clinical surrogate for nonresponse to MBV. These results contrast with the lack of efficacy in phase III trials of MBV prophylaxis among stem cell recipients, which were possibly due to low doses or inadequate timing of drug initiation in the study. Additional clinical and surrogate laboratory markers are needed to determine antiviral responses to guide MBV use. Dosage ranging studies might benefit future MBV use.
authors.affiliation: Virology Department, CHU Limoges, University Limoges, Inserm UMR-S1092, National Reference Center for Cytomegaloviruses, Limoges, France. sophie.alain@unilim.fr
authors.forename: S
authors.initials: S
authors.lastname: Alain
authors.forename: M
authors.initials: M
authors.lastname: Revest
authors.forename: D
authors.initials: D
authors.lastname: Veyer
authors.forename: M
authors.initials: M
authors.lastname: Essig
authors.forename: J P
authors.initials: JP
authors.lastname: Rerolles
authors.forename: W
authors.initials: W
authors.lastname: Rawlinson
authors.forename: C
authors.initials: C
authors.lastname: Mengelle
authors.forename: A
authors.initials: A
authors.lastname: Huynh
authors.forename: N
authors.initials: N
authors.lastname: Kamar
authors.forename: I
authors.initials: I
authors.lastname: Garrigue
authors.forename: H
authors.initials: H
authors.lastname: Kaminski
authors.forename: C
authors.initials: C
authors.lastname: Segard
authors.forename: C
authors.initials: C
authors.lastname: Presne
authors.forename: M C
authors.initials: MC
authors.lastname: Mazeron
authors.forename: V
authors.initials: V
authors.lastname: Avettant-Fenoël
authors.forename: M
authors.initials: M
authors.lastname: Lecuit
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.forename: A
authors.initials: A
authors.lastname: Coaquette
authors.forename: S
authors.initials: S
authors.lastname: Hantz
authors.forename: M
authors.initials: M
authors.lastname: Leruez-Ville
authors.forename: M-C
authors.initials: MC
authors.lastname: Ploy
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005602:France; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016377:Organ Transplantation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012263:Ribonucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole