Assessment of mitochondrial toxicity in newborns and infants with congenital cytomegalovirus infection treated with valganciclovir.
cell biology
child development
deafness
toxicology
virology
Journal
Archives of disease in childhood
ISSN: 1468-2044
Titre abrégé: Arch Dis Child
Pays: England
ID NLM: 0372434
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
20
09
2021
accepted:
17
02
2022
pubmed:
16
3
2022
medline:
22
6
2022
entrez:
15
3
2022
Statut:
ppublish
Résumé
Ganciclovir/valganciclovir is currently indicated during the first 6 months of life in symptomatic children with congenital cytomegalovirus (CMV) infection. However, this treatment may have the potential to induce mitochondrial toxicity due to off-target inhibition of DNA-polymerases. Similar anti-HIV drugs have been associated with mitochondrial toxicity but this has never been explored in CMV. To determine the potential mitochondrial toxicity profile at the genetic, functional and biogenesis level in peripheral blood mononuclear cells from a cohort of newborns and infants with symptomatic congenital CMV infection (treated with valganciclovir, untreated and uninfected controls). Longitudinal, observational and controlled study. Subjects were recruited at the tertiary referral Hospital Sant Joan de Déu and experiments were conducted at IDIBAPS-Hospital Clínic of Barcelona, Spain. CMV-infected newborns underwent comprehensive monthly clinical follow-up. Mitochondrial parameters, audiometry and neurological assessment were measured at baseline, 3-6 and 12 months after inclusion in the study. The Kruskal-Wallis test for k-independent samples and Friedman tests for repeated measurements were applied. Complex IV, citrate synthase enzymatic activities and mtDNA remained preserved in congenital CMV-infected infants treated with valganciclovir compared with controls (p>0.05 in all cases). No evidence of mitochondrial toxicity was found in infants treated with valganciclovir for congenital CMV.
Sections du résumé
BACKGROUND
Ganciclovir/valganciclovir is currently indicated during the first 6 months of life in symptomatic children with congenital cytomegalovirus (CMV) infection. However, this treatment may have the potential to induce mitochondrial toxicity due to off-target inhibition of DNA-polymerases. Similar anti-HIV drugs have been associated with mitochondrial toxicity but this has never been explored in CMV.
OBJECTIVE
To determine the potential mitochondrial toxicity profile at the genetic, functional and biogenesis level in peripheral blood mononuclear cells from a cohort of newborns and infants with symptomatic congenital CMV infection (treated with valganciclovir, untreated and uninfected controls).
DESIGN
Longitudinal, observational and controlled study.
SETTING AND PATIENTS
Subjects were recruited at the tertiary referral Hospital Sant Joan de Déu and experiments were conducted at IDIBAPS-Hospital Clínic of Barcelona, Spain. CMV-infected newborns underwent comprehensive monthly clinical follow-up.
METHODS
Mitochondrial parameters, audiometry and neurological assessment were measured at baseline, 3-6 and 12 months after inclusion in the study. The Kruskal-Wallis test for k-independent samples and Friedman tests for repeated measurements were applied.
RESULTS
Complex IV, citrate synthase enzymatic activities and mtDNA remained preserved in congenital CMV-infected infants treated with valganciclovir compared with controls (p>0.05 in all cases).
CONCLUSIONS
No evidence of mitochondrial toxicity was found in infants treated with valganciclovir for congenital CMV.
Identifiants
pubmed: 35288419
pii: archdischild-2021-322996
doi: 10.1136/archdischild-2021-322996
pmc: PMC9209682
doi:
Substances chimiques
Anti-HIV Agents
0
Antiviral Agents
0
Valganciclovir
GCU97FKN3R
Ganciclovir
P9G3CKZ4P5
Types de publication
Controlled Clinical Trial
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
686-691Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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