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Kidney Week

Abstract: PO2097

Resistant Cytomegalovirus After Kidney Transplant: Reduced Immunosuppression, High-Dose Valganciclovir, and Letermovir Prophylaxis Guided by T Cell Immunity Assessment

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Hoffman, William F., UPMC Pinnacle, Harrisburg, Pennsylvania, United States
  • Singh, Manpreet, UPMC Pinnacle, Harrisburg, Pennsylvania, United States
  • Mandel, Julie, UPMC Pinnacle, Harrisburg, Pennsylvania, United States
  • Silveira, Fernanda P., University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
Introduction

CMV infections resistant to available antivirals are associated with increased morbidity and mortality after kidney transplant.

Case Description

A 58 yo male with ADPKD underwent pre-emptive LURTx. IS included Thymoglobulin, followed by tacrolimus, mycophenolate (MMF), and prednisone. Ten days after completing 6 mos. of valganciclovir(VGCV) prophylaxis(ppx) for CMV D+/R- serostatus he developed malaise and fever; CMV PCR was 197,033 IU/ml.
VGCV 900 mg BID was started and MMF reduced. CMV PCR declined to 1399 IU/ml after 6 weeks, but then plateaued. CMV resistance testing (VGCV treatment day 62) found wild-type and mutated virus (UL54 T503I mutation and UL97 H520Q mutation) with predicted resistance to ganciclovir and cidofovir, but susceptibility to foscarnet.
MMF was stopped and VGCV was increased to 1350 mg BID (150% dose for GFR). Foscarnet was avoided due to risk of nephrotoxicity, lack of disease, and time from transplant. There was no significant leukopenia on VGCV. Over the next 2 months, CMV PCR decreased to several hundred IU/ml to Below the Limit of Quantification. Letermovir ppx was started (VGCV t. day 85) and VGCV stopped 8 days later.
CMV PCR remained negative to BLQ on letermovir. Low dose MMF was restarted. T cell immunity panel (Viracor) showed good CD8 (5.04%), but low CD4 (0.15%) response, suggesting CMV infection would recur without prophylaxis. The patient remains on letermovir ppx. Letermovir is a CYP3A inhibitor, and tacrolimus required 25% dose reduction. DSA is negative at 1 yr post-transplant; creatinine remains around 1.1 mg/dl.
Letermovir is a new CMV selective antiviral with novel mechanism of action inhibiting the viral terminase complex in late stages of replication. It is approved for prophylaxis in HCT, active against resistant strains, and not associated with myelo or nephrotoxicity.

Discussion

Resistant CMV infection is a clinical challenge. While susceptibility to foscarnet was predicted in this case, it was avoided (nephrotoxicity). Instead, immunosuppression was cautiously reduced and higher-dose VGCV was tolerated well. Once CMV viral load was negligible, a newer agent with novel mechanism of action, letermovir, was used for prophylaxis. Letermovir has been continued based on a low level of anti-CMV CD4 response, predicting high-risk for CMV recurrence.