Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis.
Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis.
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Brincidofovir 预防的 2 期临床试验中编码巨细胞病毒 DNA 聚合酶的基因突变分析。
DOI：
10.1093/infdis/jiw073
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Mommeja-Marin,Herve
中科院分区：
文献类型：
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作者：
Lanier,ERandall;Foster,Scott;Brundage,Tom;Chou,Sunwen;Prichard,MarkN;Kleiboeker,Steven;Wilson,Chad;Colville,Donella;Mommeja-Marin,Herve
Brincidofovir是一种用于预防巨细胞病毒病的口服抗病毒药物。一项比较brincidofovir与安慰剂预防造血细胞移植受者巨细胞病毒感染的2期试验的巨细胞病毒基因分型结果提供了brincidofovir临床耐药概况的初步数据。在这项研究中，在brincidofovir治疗的受试者中未检测到已知的耐药相关突变；鉴定出的基因型替换并未在体外产生对巨细胞病毒抗病毒药物的耐药性，这表明这些变化代表了与brincidofovir耐药性无关的多态性。缺乏预防期间基因型耐药的证据表明，一线使用brincidofovir预防巨细胞病毒感染可能为患者保留下游选择。
Brincidofovir is an oral antiviral in development for prevention of cytomegalovirus disease. Cytomegalovirus genotyping results from a phase 2 trial comparing brincidofovir to placebo for prophylaxis against cytomegalovirus infection in hematopoietic cell transplant recipients provided initial data on the clinical resistance profile for brincidofovir. In this study, no known resistance-associated mutations were detected in brincidofovir-treated subjects; identified genotypic substitutions did not confer resistance to cytomegalovirus antivirals in vitro, suggesting that these changes represent polymorphisms unrelated to brincidofovir resistance. Lack of evidence for genotypic resistance during prophylaxis suggests that first-line use of brincidofovir for prevention of cytomegalovirus infection may preserve downstream options for patients.