Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Adenovirus infection can lead to disease in solid organ transplant recipients, including disease of the allograft. Treatment options for severe disease are limited. Brincidofovir (BCV), a nucleotide analog, is active against human DNA viruses, including adenovirus and available for use through an open access investigational new drug (IND) protocol. We describe 3 cases of symptomatic adenovirus disease in adult renal transplant recipients successfully treated with BCV.
*Methods: This is a retrospective review of the electronic medical records of solid organ transplant recipients at our center with persistently high or rising adenovirus viral loads, with persistent fever and hemorrhagic cystitis for whom cidofovir was avoided due to risk of nephrotoxicity. BCV was obtained via IND protocol from Chimerix with FDA and institutional review board approval. All patients were treated per Chimerix’s dosing protocol and systematically monitored for side effects.
*Results: We reviewed 3 cases of adenovirus infection treated with BCV at our center between 8/2018 and 8/2019. All 3 patients were kidney transplant recipients including 2 males with history of deceased donor transplant and 1 female with living donor transplant, all 3 patients had rising Adenovirus PCR viral loads associated with hemorrhagic cystitis and were treated with BCV. The median age of the patients was 44 years (range 32 to 58 years) and the median number of days to adenoviremia detection was 347 days (range, 17 to 742 days) post-transplant. The peak viral load as determined by quantitative polymerase chain reaction (PCR) ranged from 219,000 to >10,000,000 copies/mL (median 827,000 copies/mL). No involvement of organs other than the bladder was noted in either of the reviewed cases. 1 patient received 2 doses of cidofovir prior to initiation of BCV, but was discontinued due to nephrotoxicity; the other 2 patients were treated exclusively with BCV with 1 patient also receiving adjunct IVIg. The median duration of BCV therapy was 4 weeks (range 10 days to 6 weeks) with a median time of 9 days to undetectable viremia from the 1st dose of BCV (range 7 to 23 days). All patients survived with sustained viremia clearance at 5 months follow-up. Two patients tolerated BCV with no gastrointestinal side effects and transient elevation of the transaminases to <3x the upper normal limit, which did not meet the criteria to discontinue therapy. The third patient developed diarrhea with Clostridium difficile infection and BCV was discontinued after diarrhea failed to improve on oral vancomycin therapy.
*Conclusions: BCV for adenovirus disease was well tolerated in 3 renal transplant recipients and associated with clearance of viremia in all patients.
To cite this abstract in AMA style:Zervou F, Zacharioudakis I, Mehta SA, Neumann HJ. Brincidofovir for Adenovirus Disease in Adult Renal Transplant Recipients: A Case Series [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/brincidofovir-for-adenovirus-disease-in-adult-renal-transplant-recipients-a-case-series/. Accessed March 6, 2021.
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