Preemptive versus sequential prophylactic-preemptive treatment regimens for cytomegalovirus in renal transplantation: comparison of treatment failure and antiviral resistance.
BACKGROUND
Cytomegalovirus (CMV) infections after transplantation are commonly treated using a prophylactic or preemptive regimen with (val)ganciclovir. It remains unclear, which approach is most effective in preventing CMV disease in D+R- patients. The aim of this retrospective study was to compare the treatment response and antiviral resistance in CMV infections between two treatment regimens in D+R- renal transplant recipients.


METHODS
Before 2006, a preemptive treatment regimen with valganciclovir was applied (42 patients). From 2006 onwards, patients first received prophylaxis with valganciclovir for 90 days, followed by a preemptive regimen (29 patients). CMV infections were monitored by regular determination of the CMV DNA load in plasma. Patient charts were reviewed for antiviral treatment data, and resistance was analyzed by nucleotide sequence analysis of the UL97 and UL54 genes in CMV DNA-positive samples.


RESULTS
Treatment failure, defined as a CMV DNA load more than or equal to 1000 copies/mL after at least 2 weeks of treatment, occurred less frequently in the prophylaxis cohort than in the preemptive cohort (14% vs. 71%, P<0.001). No CMV end-organ disease occurred in either cohort. Resistant viral isolates were found during treatment in one patient in the prophylaxis cohort versus in three patients in the preemptive group. All CMV infections with resistant virus were cleared without switch of (val)ganciclovir treatment.


CONCLUSIONS
Treatment failure of CMV infections occurred less frequently in D+R- renal transplant patients on a sequential prophylaxis-preemptive regimen than in patients on a purely preemptive regimen. Antiviral resistance was observed infrequently and apparently played a minor role in treatment failure.
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. m.t.van_der_beek@lumc.nl
Martha T
MT
van der Beek
Stefan P
SP
Berger
Ann C T M
AC
Vossen
Caroline S
CS
van der Blij-de Brouwer
Rogier R
RR
Press
Johan W
JW
de Fijter
Eric C J
EC
Claas
Aloys C M
AC
Kroes
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077552:Basiliximab; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000187:drug effects* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D000077561:Daclizumab; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D015994:Incidence; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D017211:Treatment Failure; D000077562:Valganciclovir
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D000077561:Daclizumab; D000077562:Valganciclovir; D015774:Ganciclovir