Assessment of mitochondrial toxicity in newborns and infants with congenital cytomegalovirus infection treated with valganciclovir
Ortiz-Gracia, Alba (Universitat Autònoma de Barcelona)
Ríos, María (Institut de Recerca Sant Joan de Déu)
Tobías, Ester (Hospital Clínic i Provincial de Barcelona)
Noguera-Julian, Antoni (Red de Investigación Translacional en Infectología Pediátrica (RITIP))
García-García, Francesc Josep (Hospital Clínic i Provincial de Barcelona)
Cantó-Santos, Judith (Hospital Clínic i Provincial de Barcelona)
Valls-Roca, Laura (Hospital Clínic i Provincial de Barcelona)
Garrabou, Glòria (Hospital Clínic i Provincial de Barcelona)
Grau, Josep M. (Hospital Clínic i Provincial de Barcelona)
Cardellach, Francesc (Hospital Clínic i Provincial de Barcelona)
Sánchez, Emilia (Universitat Ramon Llull)
Morén, Constanza (Hospital Clínic i Provincial de Barcelona)
Fortuny Guasch, Claudia (Red de Investigación Translacional en Infectología Pediátrica (RITIP))

Date:	2022
Abstract:	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. Some antivirals are associated with mitochondrial toxicity due to off-target inhibition of DNA-polymerases. This study looks for evidence of mitochondrial toxicity in infants with congenital CMV infection, treated with valganciclovir. In a series of experiments no evidence of mitochondrial toxicity was found.
Grants:	Instituto de Salud Carlos III PI17/00359 Ministerio de Economía y Competitividad PI13/01738
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cell biology ; Child development ; Deafness ; Toxicology ; Virology
Published in:	Archives of Disease in Childhood, Vol. 107 (march 2022) , p. 686-691, ISSN 1468-2044

DOI: 10.1136/archdischild-2021-322996
PMID: 35288419

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