Sunwen Chou,Drew J Winston,Robin K Avery,Catherine Cordonnier,Rafael F Duarte,Shariq Haider,Johan Maertens,Karl S Peggs,Carlos Solano,Jo-Anne H Young,Joan Gu,Ginger Pocock,Genovefa A Papanicolaou
{"title":"治疗巨细胞病毒感染的随机 3 期临床试验中出现的马立巴韦和更昔洛韦耐药性对比。","authors":"Sunwen Chou,Drew J Winston,Robin K Avery,Catherine Cordonnier,Rafael F Duarte,Shariq Haider,Johan Maertens,Karl S Peggs,Carlos Solano,Jo-Anne H Young,Joan Gu,Ginger Pocock,Genovefa A Papanicolaou","doi":"10.1093/infdis/jiae469","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nAmong 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.\r\n\r\nMETHODS\r\nViral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment.\r\n\r\nRESULTS\r\nPrior 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) 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). 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 re-treatment with an alternative CMV antiviral drug.\r\n\r\nCONCLUSION\r\nAfter 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy.\r\n\r\nCLINICAL TRIALS REGISTRATION\r\nNCT02927067 (AURORA).","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection.\",\"authors\":\"Sunwen Chou,Drew J Winston,Robin K Avery,Catherine Cordonnier,Rafael F Duarte,Shariq Haider,Johan Maertens,Karl S Peggs,Carlos Solano,Jo-Anne H Young,Joan Gu,Ginger Pocock,Genovefa A Papanicolaou\",\"doi\":\"10.1093/infdis/jiae469\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND\\r\\nAmong 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.\\r\\n\\r\\nMETHODS\\r\\nViral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment.\\r\\n\\r\\nRESULTS\\r\\nPrior 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) 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). 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 re-treatment with an alternative CMV antiviral drug.\\r\\n\\r\\nCONCLUSION\\r\\nAfter 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy.\\r\\n\\r\\nCLINICAL TRIALS REGISTRATION\\r\\nNCT02927067 (AURORA).\",\"PeriodicalId\":501010,\"journal\":{\"name\":\"The Journal of Infectious Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Infectious Diseases\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiae469\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Infectious Diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/infdis/jiae469","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection.
BACKGROUND
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.
METHODS
Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment.
RESULTS
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) 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). 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 re-treatment with an alternative CMV antiviral drug.
CONCLUSION
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).