Purpose: Ganciclovir-resistant cytomegalovirus (GR-CMV) is serious complication after transplantation. Recurrence after primary GR-CMV infection is common, with literature defined rates of approximately 20-30%. It is unknown if recurrent CMV infections in patients with historical GR-CMV maintain resistance upon virus reactivation, or if the virus can revert back to a wild-type, ganciclovir-susceptible strain.

Methods: Adult transplant recipients with documented GR-CMV viremia via genetic sequencing from 1/1/2011–7/1/2017 were evaluated. The primary endpoint was the re-demonstration of resistance during episodes of recurrent viremia.

Results: A total of 23 patients were screened; 14 were excluded due to lack of repeat genetic resistance testing during episodes of repeat viremia and 4 due to lack of viremic clearance between testing, leaving 5 for evaluation. Median CMV viral load (VL) at time of primary diagnosis of ganciclovir resistance was 10,814 IU/mL. All patients had mutations at UL97, none at UL54. Duration of negativity between clearance of primary disease and recurrence was 72 ± 129 days. Median VL at recurrence detection was 363 IU/mL. Four patients demonstrated the same resistance mutation as during their primary infection. One patient did not have resistance to UL97 or UL54 on repeat testing. Median VL at time of genetic testing was 3,720 IU/mL. VL at time of resistance testing in the patient with ganciclovir-susceptibility was 11,000 IU/mL. Of these 5 patients, 2 went on to a documented second CMV recurrence. Mean duration of negativity in these patients was 12±3 days. Median VL at recurrence was 408 IU/mL. Repeat resistance testing did not demonstrate any mutations at UL97 or UL54, suggesting reversion to wild-type in both patients. Median VL at time of resistance testing was 1905 IU/mL and therefore would be considered to be adequate for genotyping.

Conclusion: In this small case series of transplant recipients it appears that ganciclovir-resistance can be maintained during viral latency. However, we demonstrate here for the first time that the genotype of recurrent viremia may be of wild-type rather than resistant CMV. This finding is clinically important, and suggests that repeat genetic testing in patients with recurrent CMV viremia is necessary, even if ganciclovir resistance was previously demonstrated.

CITATION INFORMATION: Fose J., Jorgenson M., Degrave Z., Redfield R., Smith J., Mandelbrot D. Recovery of Wild-Type Genotype after Documented Ganciclovir-Resistance in Transplant Recipients with Recurrent CMV Viremia Am J Transplant. 2017;17 (suppl 3).

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