Chou Sunwen, Winston Drew J, Avery Robin K, Cordonnier Catherine, Duarte Rafael F, Haider Shariq, Maertens Johan, Peggs Karl S, Solano Carlos, Young Jo-Anne H, Gu Joan, Pocock Ginger, Papanicolaou Genovefa A
Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA.
Research and Development Service, Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
J Infect Dis. 2025 Mar 17;231(3):e470-e477. doi: 10.1093/infdis/jiae469.
Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively. Development of maribavir and ganciclovir resistance was compared after receiving either drug.
Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and posttreatment.
Prior antiviral drug exposure was limited, with only 2 instances of baseline drug resistance detected. An equal number (n = 241) received valganciclovir or maribavir for at least 21 days (median, 55-56 days). Among them, drug resistance mutations were detected in 24 (10%) maribavir recipients at 35-125 days (median, 56 days) after starting therapy, including in 12 of 14 who experienced a viral load rebound while on therapy. Ganciclovir resistance mutations developed in 6 (2.5%) valganciclovir recipients at 66-110 days (median, 90 days). One maribavir recipient developed a novel UL97 gene mutation (P-loop substitution G343A) that conferred strong maribavir and ganciclovir resistance in vitro. Viral clearance was confirmed in 17 (74%) of 23 patients with emergent maribavir resistance after retreatment with an alternative CMV antiviral drug.
After 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy. Clinical Trials Registration. NCT02927067 (AURORA).
在547例接受马立巴韦或缬更昔洛韦治疗造血细胞移植后首次发作的巨细胞病毒感染的患者中，治疗有效率分别为69.6%和77.4%。比较接受这两种药物治疗后马立巴韦和更昔洛韦耐药性的发生情况。
在基线和治疗后分析血浆DNA提取物中赋予耐药性的病毒突变。
既往抗病毒药物暴露有限，仅检测到2例基线耐药情况。同等数量（n = 241）的患者接受缬更昔洛韦或马立巴韦治疗至少21天（中位数为55 - 56天）。其中，在开始治疗后35 - 125天（中位数为56天），24例（10%）接受马立巴韦治疗的患者中检测到耐药突变，其中14例在治疗期间病毒载量反弹的患者中有12例出现耐药突变。6例（2.5%）接受缬更昔洛韦治疗的患者在66 - 110天（中位数为90天）出现更昔洛韦耐药突变。1例接受马立巴韦治疗的患者出现一种新的UL97基因突变（P环取代G343A），该突变在体外赋予了对马立巴韦和更昔洛韦的强耐药性。23例出现马立巴韦耐药的患者中，17例（74%）在改用另一种抗巨细胞病毒抗病毒药物再次治疗后病毒清除得到证实。
治疗3 -
