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B382 - Recurrent Cytomegalovirus (CMV) Infection in Solid Organ Transplant (SOT) Patients: Incidence, Risk Factors and Outcomes

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Author Block: A. N. Mughrabi, M. A. Alshehri, D. W. Challener, R. R. Razonable, Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN
*Purpose: Recurrence of CMV infection is common in SOT recipients despite the use of secondary prophylaxis. Here, we describe the outcomes of CMV infection and identify clinical and virologic predictors of recurrence.
*Methods: Adult SOT recipients with a positive quantitative plasma CMV PCR in December 2023 were identified. The primary outcome was recurrent CMV infection, after two negative tests and after completion of anti-CMV therapy. Secondary outcomes were mortality, hospitalization, and rejection within 1 year.
*Results: Among 65 patients with CMV infection, almost half (n=32; 49.2%) developed recurrence, at a median of 43 days (21-88) after clearance of index CMV infection. However, only 9 (13.8%) were clinically significant recurrences; the majority (n=23) only had “CMV blips” (Figure 1). Age, sex, transplanted organ, D/R serostatus, and immunosuppression were similar between the recurrence and no-recurrence groups. Kidney and liver were the most common transplanted organs, and D+/R+ was the predominant serostatus, followed by D+/R-. In contrast, virologic characteristics differed between groups: the peak viral load at index infection in the recurrence group was significantly higher than in the no-recurrence group (2.98 [2.51-3.69] vs 1.86 [1.54-3.20] log10 IU/mL, p = 0.009). Moreover, the time to peak viral load during the index infection was faster among patients with recurrence (16 days [11-23]) vs. the no-recurrence group (29 days [20-32], p = 0.058). One-year all-cause mortality was low (2 deaths in no-recurrence group); there were no CMV-related deaths. One-year all-cause hospitalization and biopsy-proven rejection were comparable between groups (Table 1). In a subgroup analysis, there was no significant difference in the characteristics of SOT patients with or without clinically significant CMV recurrence.
*Conclusions: Recurrence of CMV is common in SOT recipients, but the majority were not clinically significant and did not require antiviral treatment. Higher viral load and faster time to peak viral load at index CMV episode were significant risk factors for CMV recurrence.
Baseline and Index CMV Infection Characteristics as well as 1-Year Outcomes by Recurrence Status
CharacteristicNo Recurrence (n=33)Recurrence (n=32)Total (N=65)P Value
Age at index CMV (Cytomegalovirus), in years56 (45 - 62)61 (48.75 - 64)58 (48 - 64)0.382
Induction immunosuppression:0.606
Lymphocyte-nondepleting (Basiliximab, Steroids only)56 (45 - 62)22 (68.8%)42 (64.6%)
Lymphocyte-depleting (Thymoglobulin, Alemtuzumab)13 (39.4%)10 (31.2%)23 (35.4%)
Maintenance immunosuppression at index CMV, n (%)1.000
Triple regimen (Calcineurin inhibitor + antimetabolite + steroid)26 (78.8%)26 (81.2%)52 (80%)
Dual/Mono regimen (Any 1 or 2 of the agents above)7 (21.2%)6 (18.8%)13 (20%)
Index initial VL (Viral load) (log10 IU/mL), median [IQR]1.54 (1.54 - 1.81)1.94 (1.48 - 2.60)1.57 (1.48 - 2.30)0.365
DNQ at initial viral load, n (%)20 (60.6%)14 (43.8%)34 (52.3%)0.218
Peak VL (log10 IU/mL), median [IQR] 1.86 (1.54 - 3.20)2.98 (2.51 - 3.69)2.64 (1.77 - 3.67)0.009
DNQ at peak, n (%)11 (33.3%)2 (6.2%)13 (20%)0.011
Peak occurred at initial test, n (%)20 (60.6%)9 (28.1%)29 (44.6%)0.013
Time to peak, days, median [IQR], in patients whose VL peaked after initial test29 (20 - 32)16 (11 - 23)20 (13.75 - 29.25)0.058
Index episode length, days, median [IQR]68 (35 - 136)44.5 (37 - 73.75)54 (36 - 91)0.270
Index CMV phenotype (asymptomatic / syndrome / EOD), n (%) per level:1.000
Asymptomatic23 (69.7%)23 (71.9%)46 (70.8%)
Syndrome8 (24.2%)8 (25%)16 (24.6%)
EOD2 (6.1%)1 (3.1%)3 (4.6%)
Any antiviral treatment given for index CMV, n (%) 20 (60.6%)30 (93.8%)50 (76.9%)0.002
Total index treatment duration, days, median [IQR]55 (38 - 93)35 (29- 53)39 (32- 73)0.061
Resistance test sent, n (%)2 (6.1%)0 (0%)2 (3.1%)0.492
Secondary prophylaxis used, n (%)11 (33.3%)6 (18.8%)17 (26.2%)0.260
Secondary prophylaxis agent, n (% of prescribed) per level:0.676
Valganciclovir8 (72.7%)6 (100%)14 (82.4%)
Letermovir2 (18.2%)0 (0%)2 (11.8%)
Valganciclovir then Letermovir1 (9.1%)0 (0%)1 (5.9%)
Duration of secondary prophylaxis, median [IQR]56 (28 - 132)22 (16 - 25)37 (14 - 68)0.108
Hospitalized within 1 year (excluding any index CMV hospitalization), n (%)16 (48.5%)17 (53.1%)33 (50.8%)0.806
Biopsy-proven graft rejection within 1 year (excluding ≤30 d from index), n (%)6 (18.2%)3 (9.4%)9 (13.8%)0.475
All-cause mortality within 1 year, n (%)2 (6.1%)0 (0%)2 (3.1%)0.492
CMV-related mortality within 1 year, n (%)0 (0%)0 (0%)0 (0%)-