Publication:
Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance.

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Date

2017-03-16

Authors

Lopez-Aladid, Ruben
Guiu, Alba
Sanclemente, Gemma
Lopez-Medrano, Francisco
Cofan, Frederic
Mosquera, M Mar
Torre-Cisneros, Julian
Vidal, Elisa
Moreno, Asuncion
Aguado, Jose Maria

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Elsevier
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Abstract

Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis ≥6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients.

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MeSH Terms

Adult
Aged
Cytomegalovirus
Cytomegalovirus infections
DNA, viral
Drug resistance, viral
Female
Genotype
Humans
Male
Middle aged
Mutation
Prospective studies
Sequence analysis, DNA
Transplant recipients
Transplants

DeCS Terms

ADN viral
Análisis de secuencia de ADN
Farmacorresistencia viral
Genotipo
Infecciones por Citomegalovirus
Mutación
Receptores de trasplantes
Trasplantes

CIE Terms

Keywords

Cytomegalovirus, Genotypic analysis, Solid organ transplantation, Suspected resistance

Citation

López-Aladid R, Guiu A, Sanclemente G, López-Medrano F, Cofán F, Mosquera MM, et al. Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance. J Clin Virol. 2017 May;90:57-63