Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection.
J Infect Dis
; 2024 Sep 20.
Article
em En
| MEDLINE
| ID: mdl-39302855
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.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).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos