CMV Landscape
Cytomegalovirus (CMV) is among the most significant pathogens that can complicate solid organ transplantation (SOT), particularly in high-risk cases having seronegative recipients and seropositive donors. Without antiviral prophylaxis, CMV infection develops in many high-risk SOT recipients and can lead to viremia, disease, and organ damage.1
Antivirals Do Not Fully Mitigate the Risk of CMV2
The standard antivirals selected to combat CMV infection, whether as monotherapy or in combination with a CMV intravenous immunoglobulin (CMV-IGIV), are ganciclovir or valganciclovir.3
Antiviral drugs are unable to prevent free virus particles from infecting healthy cells2
- Although antiviral drugs block viral replication within the host cell, they cannot destroy intracellular or extracellular viruses, which may result in a rebound effect when antiviral therapy is discontinued4
- A limitation of antivirals is that they may be withdrawn due to poor antiviral activity or toxicity2,4
Although antiviral monotherapy has reduced CMV rates, CMV prevention continues to be a challenge.5
In Adult SOT Recipients
Standard of Care Guidelines Recommend CMV Prevention Approaches According to the Specific Organ3
Recommended Approaches for CMV Prevention in Different Organs in Adult SOT3
| Organ | Serostatus | Risk level | Recommended | Alternative |
|---|---|---|---|---|
| All | D–/R– | Low | Monitoring for clinical symptoms; consider antiviral prophylaxis against other herpes infections |
Preemptive therapy (if higher risk, ie, significant transfusions) |
| Kidney | D+/R– | High | 6 months of GCV/VGCV OR preemptive therapy | |
| R+ | Intermediate | 3 months of VGCV OR preemptive therapy | ||
| Liver | D+/R– | High |
3-6 months of VGCV (VGCV not FDA approved in liver) OR preemptive therapy |
|
| R+ | Intermediate |
3 months of VGCV (VGCV not FDA approved in liver) OR preemptive therapy |
||
| Pancreas | D+/R– | High | 3-6 months of VGCV | Preemptive therapy |
| R+ | Intermediate | 3 months of VGCV OR preemptive therapy | ||
| Islet | D+/R– | Intermediate | 3 months of VGCV | Preemptive therapy |
| R+ | Intermediate |
3 months of VGCV (VGCV not FDA approved in liver) OR preemptive therapy |
||
| Heart | D+/R– | High | 3-6 months of GCV/VGCV |
– Preemptive therapy – Some experts add CMV Ig to prophylaxis |
| R+ | Intermediate | 3 months of GCV/VGCV OR preemptive therapy | ||
| Lung | D+/R– | High |
6-12 months of GCV/VGCV – Some experts add CMV Ig to prophylaxis |
Preemptive therapy |
| R+ | Intermediate | Minimum 6 months of GCV/VGCV | ||
| Intestinal, composite tissue | D+/R– | High | Minimum 6 months GCV/VGCV +/– surveillance after prophylaxis | – Preemptive therapy – Some experts add CMV Ig |
| R+ | High | 3-6 months GCV/VGCV +/– surveillance after prophylaxis |
SOT, solid organ transplant; D–, donor CMV-negative serostatus; R–, recipient CMV-negative serostatus; D+, donor CMV-positive serostatus; R+, recipient CMV-positive serostatus; GCV/VGCV, oral ganciclovir/oral valganciclovir; FDA, Food and Drug Administration; CMV Ig, cytomegalovirus immunoglobulin.
References: 1. Haidar G, Boeckh M, Singh N. Cytomegalovirus infection in solid organ and hematopoietic cell transplantation: state of the evidence. J Infect Dis. 2020;221(Suppl 1):S23-S31. 2. Majewska A, Młynarczyk-Bonikowska B, Malejczyk M, Majewski S, Młynarczyk G. Possibilities of prevention and treatment of human cytomegalovirus infections including new drugs and compounds with potential application. Advancements Microbiol. 2019:58(3):291-299. 3. Kotton CN, Kumar D, Caliendo AM. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018;102(6):900-931. 4. Acosta E, Bowlin T, Brooks J, et al. Advances in the development of therapeutics for cytomegalovirus infections. J Infect Dis. 2020;221(Suppl 1):S32-S44. 5. Grossi PA, Mohacsi P, Szabolcs Z, Potena L. Cytomegalovirus immunoglobulin after thoracic transplantation: an overview. Transplantation. 2016;100(Suppl 3):S1-S4.