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BACKGROUND: This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24% respectively cleared cytomegalovirus DNA at week 8 (treatment responders). METHODS: Baseline and post-treatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54 and UL27. RESULTS: At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n=1) and UL97 F342Y (n=3). Post-treatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 non-responders and 25 (86%) of the 29 non-responders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n=34), H411Y (n=26) and C480F (n=21), first detected 26 to 130 (median 56) days after starting maribavir. CONCLUSIONS: Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance. CLINICAL TRIALS REGISTRATION: NCT02931539 (SOLSTICE).

PMID: 37506264