The Journal of infectious diseases · 2025
Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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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
Аннотация
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 posttreatment.
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 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.
CONCLUSIONS: 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).
METHODS: Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and posttreatment.
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 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.
CONCLUSIONS: 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).