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
In solid organ transplant recipients2
CMV Seroprevalence is high in the general population and extends to one-half of high-risk solid organ transplant (SOT) recipients3
In the United States, CMV seroprevalence in the adult population is estimated to be 75%. Globally, CMV seroprevalence is estimated to be 83% in the general population.4
More than 50% of US adults have been infected with CMV by age 40, and CMV seroprevalence increases with age.5,6
Cytomegalovirus (CMV) still occurs in up to 50% of high-risk solid organ transplant (SOT) patients. Post-transplant, CMV infection can have significant direct and indirect effects on transplant outcomes, but prevention strategies decrease the risk of CMV disease.7
The Risk of CMV Disease Is Associated With CMV Seroprevalence Status4
In solid organ transplantation (SOT), the risk varies based on whether the organ donor is CMV-seropositive (D+) or CMV-seronegative (D−) and whether the organ recipient is CMV-seropositive (R+) or CMV-seronegative (R−).4
D, donor; R, recipient; +, CMV-seropositive; –, CMV-seronegative.
CMV +/– Serostatus Is Independently Associated With Worse Allograft and Patient Survival in SOT8
In a large study (N=22,461) of SOT patients separated according to seroprevalence status, 10 years after transplantation, the 73.6% survival rate (95% CI, 72.3, 74.9) for the D–/R– group was significantly higher (P<0.0001) than all the other groups combined (66.1% [65.3, 66.9])8
The High-Risk CMV D+/R– Group Had Significantly Lower Patient Survival vs Low-Risk CMV D–/R– Patients8
D, donor; R, recipient; +, CMV-seropositive; –, CMV-seronegative.
STUDY DESIGN: From the UK Transplant Registry, Desai and colleagues identified all recipients of kidney, liver, heart, and lung transplants in the United Kingdom between 1987 and 2007 with known CMV immunoglobulin G status. Recipients were classified according to donor (D) and recipient (R) serostatus: high-risk (D+/R−), intermediate-risk (D+/R+ or D−/R+), and low-risk (D−/R−). Therefore, recipients were divided into 4 groups: D−/R−, D−/R+, D+/R+ and D+/R−. Cancer data were obtained from the Office for National Statistics. The impact of CMV infection on survival and cancer incidence was assessed.8
In the United States
The Proportion of High-Risk CMV D+/R– Patients in the SOT Population Continues to Increase
Over a span of 22 years, the prevalence of CMV D+/R– in kidney, lung, heart, and liver solid organ transplant (SOT) recipients, respectively, increased significantly and is projected to continue to increase.9
Observed Average Increase and Predicted Increase of CMV D+/R– SOT Patients Over 40 Years (SRTR)
avg, average; CMV, cytomegalovirus; D+/R–, donor positive/recipient negative
Over 4 decades, the predicted percentage increase in SOT D+/R– CMV prevalence from the year 2000 to 2040 is:
Kidney: 2.6% increase
Lung: 9.0% increase
Heart: 9.3% increase
Liver: 10.4% increase
CMV, cytomegalovirus; D+/R–, donor positive/recipient negative.
STUDY DESIGN: Imlay and colleagues obtained donor (D) and recipient (R) CMV serostatus and demographic factors from the Scientific Registry of Transplant Recipients for persons ≥18 years undergoing a first SOT between January 1, 2000 and December 31, 2020 in the United States. The proportions of D+/R– SOTs over time were assessed using Chi square for trend and modeled through 2040. Factors associated with D/R seropositivity were assessed using logistic models.9
The increasing prevalence of D+/R– transplants necessitates further CMV preventive strategies.9,10
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. Downes KJ, Sharova A, Boge CLK, et al. CMV infection and management among pediatric solid organ transplant recipients. Pediatric Transplant. 2022;26(3):e14220. doi:10.1111/petr.14220. 3. Hernandez C, Mabilangan C, Burton C, Doucette K, Preiksaitis J. Cytomegalovirus transmission in mismatched solid organ transplant recipients: Are factors other than anti-viral prophylaxis at play? Am J Transplant. 2021;21:3958–3970. doi:10.1111/ajt.16734 4. Zuhair M, Smit GSA, Wallis G et al. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev Med Virol. 2019;e2034. doi:10.1002/rmv.2034 5. Centers for Disease Control and Prevention. About Cytomegalovirus (CMV). https://www.cdc.gov/cmv/overview.html. Accessed February 9, 2024. 6. Fowler K, Mucha J, Neumann M, et al. A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development. BMC Public Health. 2022;22:1659. doi:10.1186/s12889-022-13971-7 7. Kotton CN, Kamar N. New insights on CMV management in solid organ transplant patients: prevention, treatment, and management of resistant/refractory disease. Infect Dis Ther. 2023;12:333-342. doi:10.1007/s40121-022-00746-1 8. Desai R, Collett D, Watson CJE, Johnson PJ, Moss P, Neuberger J. Impact of cytomegalovirus on long-term mortality and cancer risk after organ transplantation. Transplantation. 2015;99:1989-1994. 9. Imlay H, Wagener MM, Vutien P, Perkins J, Singh N, Limaye AP. Increasing proportion of high-risk cytomegalovirus donor-positive/recipient-negative serostatus in solid organ transplant recipients. Transplantation. 2023;107(4):988-993. 10. Grossi PA, Kamar N, Saliba F, et al. Cytomegalovirus management in solid organ transplant recipients: a pre-COVID-19 survey from the Working Group of the European Society for Organ Transplantation. Transpl Int. 2022;35:10332. doi:10.3389/ti.2022.10332