Trial reportThe Journal of infectious diseases2014
Phenotypic evaluation of previously uncharacterized cytomegalovirus DNA polymerase sequence variants detected in a valganciclovir treatment trial.
Trial report in The Journal of infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients.The Journal of infectious diseases · 2024Trial
- A new locus of foscarnet resistance in the cytomegalovirus UL54 DNA polymerase gene among uncharacterized mutations in recent clinical trials.Antiviral research · 2026Article
- Safety and efficacy of immunoguided prophylaxis for cytomegalovirus disease in low-risk lung transplant recipients in Spain: a multicentre, open-label, randomised, phase 3, noninferiority trial.The Lancet regional health. Europe · 2025Article
- Practical updates in clinical antiviral resistance testing.Journal of clinical microbiology · 2024Review
- Phenotypes of cytomegalovirus genetic variants encountered in a letermovir clinical trial illustrate the importance of genotyping validation.Antiviral research · 2024Article
- Impact of Amino Acid Substitutions in Region II and Helix K of Herpes Simplex Virus 1 and Human Cytomegalovirus DNA Polymerases on Resistance to Foscarnet.Antimicrobial agents and chemotherapy · 2021Article
- Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance.Antiviral research · 2020Review
- Hypersusceptibility of Human Cytomegalovirus to Foscarnet Induced by Mutations in Helices K and P of the Viral DNA Polymerase.Antimicrobial agents and chemotherapy · 2020Article
- Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Foscarnet resistance mutations mapping to atypical domains of the cytomegalovirus DNA polymerase gene.Antiviral research · 2017Article
- Rapid In Vitro Evolution of Human Cytomegalovirus UL56 Mutations That Confer Letermovir Resistance.Antimicrobial agents and chemotherapy · 2015Article
- Approach to drug-resistant cytomegalovirus in transplant recipients.Current opinion in infectious diseases · 2015Review
- Improved detection of emerging drug-resistant mutant cytomegalovirus subpopulations by deep sequencing.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIn a large randomized trial comparing oral valganciclovir and intravenous ganciclovir for treatment of cytomegalovirus disease in solid organ transplantation, confirmed genotypic drug resistance was uncommon (<5%), but definitive interpretation was limited by the detection of 110 uncharacterized UL54 viral DNA polymerase sequence variants.
methodsBased on treatment history and genetic locus of the sequence changes, 39 of the sequence variants were prioritized for recombinant phenotyping by construction of cloned viral mutants and drug susceptibility testing in cell culture.
resultsFour amino acid substitutions were newly confirmed to alter ganciclovir susceptibility: A505V and I726T conferred a borderline decrease in ganciclovir and cidofovir susceptibility, while Q578L and G841S conferred slightly decreased ganciclovir and foscarnet susceptibility. A nonviable phenotype was found for 8 mutations distributed among amino terminal, exonuclease and catalytic domains. Retesting of stored study specimens could not confirm the original detection of >20 sequence variants, including the nonviable mutations and several resistance mutations.
conclusionsNewly phenotyped UL54 sequence variants did not significantly change the reported incidence of drug resistance in the clinical trial. Unrecognized sequence variants in diagnostic genotyping reports should be confirmed by additional testing in order to improve clinical decision making.
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