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Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2024 Sep 20. Date of Electronic Publication: 2024 Sep 20. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- 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.<br />Methods: Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment.<br />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.<br />Conclusion: After 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy.<br />Clinical Trials Registration: NCT02927067 (AURORA).<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Details
- Language :
- English
- ISSN :
- 1537-6613
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 39302855
- Full Text :
- https://doi.org/10.1093/infdis/jiae469