Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 18, Issue 12, Pages 3060-3064Publisher
WILEY
DOI: 10.1111/ajt.15135
Keywords
antibiotic: antiviral; antibiotic: antiviral-ganciclovir/valganciclovir; clinical research/practice; infection and infectious agents - viral: Cytomegalovirus (CMV); infectious disease; off-label drug use; translational research/science
Categories
Funding
- National Institute of Allergy and Infectious Diseases [R01 AI-116635]
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Following a year of valganciclovir prophylaxis, a lung transplant recipient developed cytomegalovirus (CMV) infection that became resistant to ganciclovir, as confirmed by detection of UL97 kinase mutation M460V and a previously uncharacterized UL54 DNA polymerase mutation L516P. The latter mutation is now shown to confer ganciclovir and cidofovir resistance. As predicted from the viral genotype, foscarnet therapy was effective, but resumption of valganciclovir as secondary prophylaxis resulted in a plasma viral load rebound to 3.6 log(10) copies/mL several weeks later. Valganciclovir was then replaced by letermovir, resulting in gradual viral load reduction in the first 5 weeks to below the quantitation limit (2.7 log(10) copies/mL) for 1 week, followed by 10 weeks of rising viral loads reaching 4.3 log(10) copies/mL while on letermovir. At this point, CMV genotypic testing revealed UL56 mutation C325Y, which confers absolute resistance to letermovir. Retreatment with foscarnet was successful. This case adds to the considerable list of proven ganciclovir resistance mutations, and provides an early experience with letermovir resistance after off-label therapeutic use. This experience is consistent with in vitro observations of rapid emergence of letermovir-resistant CMV after drug exposure.
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