Does the Use of Serum Ganciclovir Levels to Adjust Valganciclovir Dosing Prevent the Development of CMV Resistance in CMV Mismatched Heart Transplant Recipients? The Mid America Experience

• Published in: The Journal of heart and lung transplantation Vol. 38; no. 4; p. S119
• Main Authors: Linard, J., Knutson, C., Wells, R., Borkon, A.M., Kao, A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-04-2019
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2019.01.280

Cytomegalovirus (CMV) infection can lead to devastating sequelae post heart transplant (HTx), such as organ invasive disease, rejection and coronary allograft vasculopathy. CMV naive HTx patients (pts) who receive organs from CMV positive donors are at very high risk for CMV-related complications. The standard prophylaxis is renally-dosed valganciclovir (VAL) for 12 months, but this one-size-fits-all approach may lead to inadequate serum ganciclovir (GCV) levels, predisposing the pts to VAL resistance.
We conducted a retrospective chart review of HTx pts who were CMV recipient negative/donor positive from 12/15-9/18. We started using serum trough GCV levels to guide VAL dosing in 6/17, aiming for trough level of 0.35-0.7 mcg/mL. Pts followed before protocol implementation were in group A and pts who had GCV levels drawn proactively any time during their first year post HTx were in group B. GCV trough levels were checked at 2 weeks, 3 and 6 months, as well as 2 weeks after GCV dose adjustment. CMV viremia was defined as ≥ 137 IU/mL.
This retrospective study included 29 pts (5 women, mean age 56.3±12.4 years). Group A had 8 pts and group B had 21 pts. 5 pts in group A developed CMV viremia, and 3 developed VAL resistance, requiring treatment with cidofovir or foscarnet. For group B pts, GCV levels ranged from 0.1 to 1.9 mcg/mL. 10 pts achieved therapeutic GCV levels on standard VAL dosing. The other pts required VAL dosing adjustments in increments of 450 mg (maximum 1350 mg/day). 5 pts with levels higher than 0.9 mcg/mL developed leukopenia and VAL dose was adjusted. 3 group B pts developed CMV viremia prior to establishing goal GCV trough levels but none developed CMV resistance. At the end of year 1, CMV IgG was tested, and VAL continued until seroconversion occurred. One pt who remained CMV IgG negative developed viremia when VAL was inadvertently discontinued at 1 year.
Given the increasing frequency of CMV resistance in HTx pts, we began using trough GCV level-guided VAL dosing instead of standard dosing in 6/17. Our initial experience showed 3/8 seronegative pts developed VAL resistance using standard dosing, whereas 0/21 pts developed VAL resistance using GCV level to adjust VAL dosing. These encouraging findings will warrant a larger experience for confirmation.