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Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection

Genotypically resistant cytomegalovirus (CMV) infection is associated with increased morbi-mortality. We herein aimed at understanding the factors that predict CMV genotypic resistance in refractory infections and disease in the SOTR (Solid Organ Transplant Recipients) population, and the factors as...

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Autores principales: Tamzali, Yanis, Pourcher, V., Azoyan, L., Ouali, N., Barrou, B., Conti, F., Coutance, G., Gay, F., Tourret, J., Boutolleau, D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10307959/
https://www.ncbi.nlm.nih.gov/pubmed/37398559
http://dx.doi.org/10.3389/ti.2023.11295
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author Tamzali, Yanis
Pourcher, V.
Azoyan, L.
Ouali, N.
Barrou, B.
Conti, F.
Coutance, G.
Gay, F.
Tourret, J.
Boutolleau, D.
author_facet Tamzali, Yanis
Pourcher, V.
Azoyan, L.
Ouali, N.
Barrou, B.
Conti, F.
Coutance, G.
Gay, F.
Tourret, J.
Boutolleau, D.
author_sort Tamzali, Yanis
collection PubMed
description Genotypically resistant cytomegalovirus (CMV) infection is associated with increased morbi-mortality. We herein aimed at understanding the factors that predict CMV genotypic resistance in refractory infections and disease in the SOTR (Solid Organ Transplant Recipients) population, and the factors associated with outcomes. We included all SOTRs who were tested for CMV genotypic resistance for CMV refractory infection/disease over ten years in two centers. Eighty-one refractory patients were included, 26 with genotypically resistant infections (32%). Twenty-four of these genotypic profiles conferred resistance to ganciclovir (GCV) and 2 to GCV and cidofovir. Twenty-three patients presented a high level of GCV resistance. We found no resistance mutation to letermovir. Age (OR = 0.94 per year, IC95 [0.089–0.99]), a history of valganciclovir (VGCV) underdosing or of low plasma concentration (OR= 5.6, IC95 [1.69–20.7]), being on VGCV at infection onset (OR = 3.11, IC95 [1.18–5.32]) and the recipients’ CMV negative serostatus (OR = 3.40, IC95 [0.97–12.8]) were independently associated with CMV genotypic resistance. One year mortality was higher in the resistant CMV group (19.2 % versus 3.6 %, p = 0.02). Antiviral drugs severe adverse effects were also independently associated with CMV genotypic resistance. CMV genotypic resistance to antivirals was independently associated with a younger age, exposure to low levels of GCV, the recipients’ negative serostatus, and presenting the infection on VGCV prophylaxis. This data is of importance, given that we also found a poorer outcome in the patients of the resistant group.
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spelling pubmed-103079592023-06-30 Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection Tamzali, Yanis Pourcher, V. Azoyan, L. Ouali, N. Barrou, B. Conti, F. Coutance, G. Gay, F. Tourret, J. Boutolleau, D. Transpl Int Health Archive Genotypically resistant cytomegalovirus (CMV) infection is associated with increased morbi-mortality. We herein aimed at understanding the factors that predict CMV genotypic resistance in refractory infections and disease in the SOTR (Solid Organ Transplant Recipients) population, and the factors associated with outcomes. We included all SOTRs who were tested for CMV genotypic resistance for CMV refractory infection/disease over ten years in two centers. Eighty-one refractory patients were included, 26 with genotypically resistant infections (32%). Twenty-four of these genotypic profiles conferred resistance to ganciclovir (GCV) and 2 to GCV and cidofovir. Twenty-three patients presented a high level of GCV resistance. We found no resistance mutation to letermovir. Age (OR = 0.94 per year, IC95 [0.089–0.99]), a history of valganciclovir (VGCV) underdosing or of low plasma concentration (OR= 5.6, IC95 [1.69–20.7]), being on VGCV at infection onset (OR = 3.11, IC95 [1.18–5.32]) and the recipients’ CMV negative serostatus (OR = 3.40, IC95 [0.97–12.8]) were independently associated with CMV genotypic resistance. One year mortality was higher in the resistant CMV group (19.2 % versus 3.6 %, p = 0.02). Antiviral drugs severe adverse effects were also independently associated with CMV genotypic resistance. CMV genotypic resistance to antivirals was independently associated with a younger age, exposure to low levels of GCV, the recipients’ negative serostatus, and presenting the infection on VGCV prophylaxis. This data is of importance, given that we also found a poorer outcome in the patients of the resistant group. Frontiers Media S.A. 2023-06-15 /pmc/articles/PMC10307959/ /pubmed/37398559 http://dx.doi.org/10.3389/ti.2023.11295 Text en Copyright © 2023 Tamzali, Pourcher, Azoyan, Ouali, Barrou, Conti, Coutance, Gay, Tourret and Boutolleau. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Health Archive
Tamzali, Yanis
Pourcher, V.
Azoyan, L.
Ouali, N.
Barrou, B.
Conti, F.
Coutance, G.
Gay, F.
Tourret, J.
Boutolleau, D.
Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection
title Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection
title_full Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection
title_fullStr Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection
title_full_unstemmed Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection
title_short Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection
title_sort factors associated with genotypic resistance and outcome among solid organ transplant recipients with refractory cytomegalovirus infection
topic Health Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10307959/
https://www.ncbi.nlm.nih.gov/pubmed/37398559
http://dx.doi.org/10.3389/ti.2023.11295
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