Assessment of mitochondrial toxicity in newborns and infants with congenital cytomegalovirus infection treated with valganciclovir

缬更昔洛韦治疗先天性巨细胞病毒感染新生儿和婴儿的线粒体毒性评估

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作者:Alba Ortiz-Gracia, María Ríos, Ester Tobías, Antoni Noguera-Julian, Francesc Josep García-García, Judith Cantó-Santos, Laura Valls-Roca, Glòria Garrabou, Josep Maria Grau, Francesc Cardellach, Emilia Sánchez, Constanza Morén #, Clàudia Fortuny #

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.

Conclusions

No evidence of mitochondrial toxicity was found in infants treated with valganciclovir for congenital CMV.

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.

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.

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.

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