Pompeu Fabra University, Barcelona, Spain.
Universitat Autònoma de Barcelona, Barcelona, Spain.
Arch Dis Child. 2022 Jul;107(7):686-691. doi: 10.1136/archdischild-2021-322996. Epub 2022 Mar 14.
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.
目前，对于有症状的先天性巨细胞病毒（CMV）感染患儿，在生命的前 6 个月内，推荐使用更昔洛韦/缬更昔洛韦进行治疗。然而，由于对 DNA 聚合酶的非靶向抑制，这种治疗方法可能具有诱导线粒体毒性的潜力。类似的抗 HIV 药物已被证明与线粒体毒性相关，但这在 CMV 中从未被探索过。
在患有有症状先天性 CMV 感染的新生儿和婴儿的外周血单核细胞中，从遗传、功能和生物发生水平上确定潜在的线粒体毒性特征。这些患儿分为接受缬更昔洛韦治疗、未接受治疗和未感染对照组。
纵向、观察性和对照研究。
研究对象在三级转诊医院 Sant Joan de Déu 招募，实验在西班牙 IDIBAPS-Hospital Clínic of Barcelona 进行。CMV 感染的新生儿接受了全面的每月临床随访。
在纳入研究时、3-6 个月和 12 个月后，测量线粒体参数、听力和神经评估。应用 Kruskal-Wallis 检验和 Friedman 检验进行重复测量。
与对照组相比，接受缬更昔洛韦治疗的先天性 CMV 感染婴儿的细胞色素 C 氧化酶 IV、柠檬酸合酶酶活性和线粒体 DNA 保持不变（所有情况下 p>0.05）。
在先天性 CMV 感染婴儿中使用缬更昔洛韦治疗未发现线粒体毒性的证据。
