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CMV Prophylaxis
CMV: Still Lurking Under the Bridge From Transplant to Recovery

Released: September 05, 2025

Marcus Pereira
Marcus Pereira, MD, MPH, FAST
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Key Takeaways
  • Developments in CMV prevention and treatment are providing new opportunities to mitigate the impact of the troll of transplantation.

Tremendous progress in solid organ transplantation serves to remind us that there is a lurking troll called cytomegalovirus (CMV) that is eager to leverage any opportunity to affect outcomes. For example, with an expanding armamentarium, posttransplant immunosuppression is becoming quite complex with combinations of medications potentially including steroids, calcineurin inhibitors, mycophenolic acid, cell cycle inhibitors, mTOR inhibitors, anti–T-cell antibodies, or belatacept.

The overall level of immunosuppression for transplant recipients is also determined by a combination of other factors. How sick were they before the transplant? What medications are they taking? Do they have comorbidities such as diabetes? Do they have advanced age, leukopenia, and/or hypogammaglobulinemia?

Not all of us can get CMV IgG titers. Many institutions like mine only provide a positive or negative result. A low positive IgG titer, however, means that your patient is at risk for CMV reactivation. This has been demonstrated in both kidney and liver transplant patients. So all of these factors can contribute to CMV reactivation. In fact, CMV itself can cause immunosuppression along with other opportunistic herpesviruses such as varicella zoster virus, herpes simplex virus, or even Epstein-Barr virus (EBV).

CMV Replication and Transplant Outcomes
What is the risk of CMV replication in solid organ transplant recipients? Patients can have symptoms like CMV syndrome (which I tell my patients is generally something similar to mononucleosis) or tissue-invasive disease, which is more serious.

The effects that we see the most, however, are not necessarily the direct effects of CMV replication but the indirect effects. These include immunosuppressive effects of viral infection, as previously mentioned, along with proinflammatory effects, alloreactivity, and direct interaction with other herpesviruses. When it comes to reactivation of EBV, then you are worried about posttransplant lymphoproliferative disease. Any or all of these effects can lead to bacterial and fungal superinfections, graft dysfunction or rejection, and even mortality.

Modern Approaches
Fortunately, developments in CMV prevention and treatment are also providing new opportunities to mitigate the impact of the troll of transplantation.

For example, my center often takes a hybrid approach to CMV prevention in high-risk patients, where we give patients antiviral prophylaxis, and then after it ends, we survey the patient with serial PCR testing.

Another development is that valganciclovir is no longer the only antiviral available for prophylaxis. Letermovir, which was originally approved for CMV prevention in allogeneic hematopoietic cell transplant recipients, was extended for high-risk kidney transplant recipients in 2023. Unlike valganciclovir, letermovir is not associated with bone marrow suppression or renal toxicity. Letermovir does increase levels of tacrolimus and sirolimus.

Your Thoughts
Is CMV becoming a bigger or smaller factor for your outcomes for transplant? Let us know by leaving a comment below and check out the on-demand webcast of our recent satellite symposium at the 2025 World Transplant Congress to learn more!

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