Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients.

Details

Serval ID
serval:BIB_4030F9374C9F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients.
Journal
BMC infectious diseases
Author(s)
Perrottet N., Manuel O., Lamoth F., Venetz J.P., Sahli R., Decosterd L.A., Buclin T., Pascual M., Meylan P.
ISSN
1471-2334 (Electronic)
ISSN-L
1471-2334
Publication state
Published
Issued date
06/01/2010
Peer-reviewed
Oui
Volume
10
Pages
2
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease.
Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC.
Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mgxh/L, range for the 7 patients: 40-118 mgxh/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mgxh/L, range: 44-118 mgxh/L).
Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection.
Keywords
Aged, Antiviral Agents/therapeutic use, Cytomegalovirus Infections/drug therapy, Cytomegalovirus Infections/prevention & control, DNA, Viral/blood, Female, Ganciclovir/analogs & derivatives, Ganciclovir/blood, Ganciclovir/therapeutic use, Humans, Male, Middle Aged, Organ Transplantation, Prospective Studies, Transplantation, Homologous, Valganciclovir, Viral Load
Pubmed
Web of science
Open Access
Yes
Create date
04/10/2019 8:02
Last modification date
05/10/2019 6:26
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