Ganciclovir resistant (GCV-R) CMV is uncommon, occurring in 1-10% of solid organ transplant (SOT) recipients, but is associated with decreased renal function in part due to use of nephrotoxic second line medications and ultimately with increased mortality. Our study aims to evaluate the prevalence and associated clinical outcomes of GCV-R CMV in SOT at our center.
We obtained all CMV genotypic resistance testing from 2011 to 2016. Patient demographics, co-morbidities, immunosuppression (IS), antiviral exposure and dosing, treatment, graft and mortality outcomes were reviewed.
During the study period 35 CMV genotypes were obtained from 23 immunosuppressed patients. GCV-R was identified in 9 patients, 6 of which were renal transplant (RT) recipients (figure 1).
Among the 6 RT cases, 5 CMV D+/R- patients received valganciclovir (VGCV) prophylaxis. Median peak CMV viral load was 5.98 log. VGCV prophylaxis was underdosed in 2/5 (40%) and administered for <200 days in 2/5 (40%). CMV viremia and diagnosis of CMV resistance occurred at a median of 310.5 and 411.5 days post-transplant, respectively. All 6 patients had UL97 mutations; patient (PT) 3 also had a UL54 mutation. Treatment with foscarnet and withdrawal of mycophenolate mofetil in PT 1, 2, 4, and 6 led to resolution of viremia. PT 4 progressed to chronic renal failure. PT 3 received foscarnet followed by cidofovir but ultimately suffered graft loss. Patient 5 (CMV D-/R-) developed primary infection remote from transplant and was treated with VGCV and IS withdrawal alone.
Treatment courses were prolonged, ranging from 6 weeks to 6 months of intravenous therapy in 5/6 patients. Although all patients survived, 3/6 (50%) experienced rejection following CMV infection, 1 had decline in graft function and 1 had graft loss.
CMV resistance is uncommon but associated with poor graft outcomes in RT recipients related to antiviral nephrotoxicity, reduction in IS, and direct CMV effects. Our institution has implemented a pharmacy-driven VGCV dose adjustment protocol following RT to decrease the risk of GCV-R emergence secondary to suboptimal VGCV prophylaxis. Development of new, less nephrotoxic antivirals is needed for treatment of GCV-R CMV in SOT recipients.
M. Landry, None
M. Malinis, None