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Antivir Ther. 2009;14(5):697-704.

Cytomegalovirus resistance in solid organ transplant recipients treated with intravenous ganciclovir or oral valganciclovir.

Author information

  • 1Infectious Disease Research Center of the Centre hospitalier universitaire de Québec, Québec City, QC, Canada. Guy.Boivin@crchul.ulaval.ca

Abstract

BACKGROUND:

The rate of cytomegalovirus (CMV) mutations conferring ganciclovir resistance was assessed in a trial comparing intravenous ganciclovir and oral valganciclovir for treatment of CMV disease in solid organ transplant (SOT) recipients.

METHODS:

Viral genes (UL97 and UL54) conferring ganciclovir resistance were amplified and sequenced from blood samples collected at days 0 (before therapy), 21 (end of induction) and 49 (end of maintenance).

RESULTS:

The overall risk of developing a confirmed or probable ganciclovir resistance mutation during treatment was similar for patients treated with ganciclovir (2.3%) and valganciclovir (3.6%; P=0.51). A persistent viral load at day 21 was associated with a significant risk of ganciclovir resistance by day 49 (odds ratio 11.83; P=0.022). In multivariate analyses, presence of a confirmed ganciclovir resistance mutation was independently associated with virological failure (viral load > or =600 copies/ml) at days 21 and 49. One-third (3/9) of patients with confirmed CMV resistance mutations had recurrent CMV disease. The plasma half-life of confirmed ganciclovir-resistant UL97 mutants was significantly longer than that of wild-type strains, polymorphic variants and strains with mutations of unknown significance (P=0.045). Multiple UL54 mutations of unknown significance were found in clinical strains. Viral kinetic analysis of these latter strains revealed no effect (negative or positive) on in vivo viral fitness.

CONCLUSIONS:

Treatment with oral valganciclovir or intravenous ganciclovir results in similar and low rates of resistance mutations in SOT recipients. Patients with drug-resistant CMV strains often have virological failure and might have unfavourable clinical outcomes.

PMID:
19704173
[PubMed - indexed for MEDLINE]
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