Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

Abstract

Background Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT). Methods Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers’ recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors. Results Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5%) experienced prophylaxis breakthrough and 35/585 (6.0%) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95% confidence interval [CI], 2.63 to 10.98; P < 0.001) and increasing % FUT with a prophylaxis score <90 (aHR, 1.16; 95% CI, 1.04 to 1.29; P = .01 per 10% longer FUT w/ score <90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95% CI, 3.34 to 121.9; P = .001), mainly due to liver or myelotoxicity. Conclusions Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents.

Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: A systematic literature review of real‐world evidence

“…With respect to CMV risk factors, recipient age and D+/R‐ CMV serostatus were found to be consistently associated with an increase in the risk of CMV infection/disease among adult KT recipients. Our findings are consistent with the prior literature 98‐100 and highlight that targeted intervention in high‐risk subpopulations may reduce the CMV burden in KT recipients. Furthermore, CMV infection/disease was associated with increased mortality and GL in adult KT recipients.…”

Letermovir prophylaxis in solid organ transplant—Assessing CMV breakthrough and tacrolimus drug interaction

“…An ideal sample size of 81 patients was found after sample size calculations were performed using a survey published in conjunction with the Infectious Diseases Society of America. 14…”

Development and Dynamics of Cytomegalovirus UL97 Ganciclovir Resistance Mutations in Transplant Recipients Detected by Next-Generation Sequencing

“…We have previously reported a higher rate of CMV breakthrough during primary prophylaxis among kidney recipients in our center due to the administration of (val)ganciclovir prophylaxis of 450 mg every other day [ 34 ], and this lower dosage may very well account for some of the UL97-GCV-R observed among the kidney recipients in the current study. The results of these two studies have prompted an increase in the administered dosage of valganciclovir prophylaxis for the kidney recipients at our center and underline the importance of optimal dosing of primary prophylaxis.…”