Characteristics and Outcomes of Cytomegalovirus Infection in Seropositive Kidney Transplant Recipients in the Era of Antiviral Prophylaxis with Valacyclovir: A Single-Center Study in Morocco

Abstract

Purpose: Despite the use of antiviral prophylaxis with valacyclovir, cytomegalovirus infection (CMV) can still occur in seropositive kidney transplant recipients. In this study, we aimed to assess the incidence of CMV DNAemia and its risk factors in Moroccan transplant recipients. Patients and Methods: Sixty kidney recipients with positive cytomegalovirus serostatus, receiving post-transplant prophylaxis were enrolled between 2013 and 2017. In total, 455 plasma samples were collected and tested for CMV DNAemia using PCR-based Abbott RealTime assays. Results: The incidence of CMV infection in seropositive patients was 63%. In patients with quantifiable DNAemia, the duration of CMV infection was significantly shorter than in those with detectable DNAemia (141.5 ± 96.9 vs 294.1 ± 112.6 days, P < 0.001). During prophylactic treatment, 14 of 30 patients (47.0%) experienced active replication with quantifiable DNAemia, whereas none of eight patients with detectable DNAemia did (P = 0.017). Patients with symptomatic DNAemia were significantly younger than those without symptoms (28.8 ± 5.12 vs 38.1 ± 12.34 years, P = 0.007). The peak viral loads were significantly associated with viral disease (odds ratio: 3.39, 95% confidence interval: 1.21-9.53, P = 0.02). The duration of DNAemia (21.2 vs 13.4 days, P = 0.028) was significantly longer in symptomatic patients. Significantly higher rates of acute rejection were exclusively observed in recipients with disease (4/8, 50% vs 0/22, 0%, P = 0.003). Conclusion:Patients with high-level DNAemia were at an increased risk of progression to disease and acute rejection. Monitoring the viral load during the first year posttransplantation is essential, to support current preventive strategies.

Infection, Rejection, and the Connection

“…Specifically, CMV viremia is associated with an increased risk of acute rejection. 21,[36][37][38][39][40][41][42] Consistent with this association, CMV antiviral prophylaxis and surveillance with pre-emptive therapy decrease the risk of rejection. 41,[43][44][45] However, one large kidney transplant study indicates that CMV contributes to acute rejection only in recipients receiving 3-drug maintenance immunosuppression.…”

“…• Viremia associated with increased risk of acute rejection 21,[36][37][38][39][40][41][42] • Reduction of immunosuppression • Antiviral prophylaxis decreases rejection risk 41,[43][44][45] • Antivirals: valganciclovir, ganciclovir, foscarnet, cidofovir, letermovir 46 • History of viremia associated with increased risk of chronic rejection 7,10,[47][48][49][50] • Donor/recipient serostatus matching 51 • Upregulates adhesion molecules promoting allograft infiltration and inflammation [52][53][54] • Modulates MHC expression [55][56][57][58][59] • Induces inflammatory NK and T cells 60,61 • Induces proinflammatory T-cell aging [62][63][64][65] BKV…”

Challenging the Conventional Interpretation of HCMV Seronegativity

“…These may be transient with control by NK cells (as in Case 2) or persistent with seroconversion blocked by vIL-10. It is clear that seropositivity is a risk factor for adverse outcomes following renal transplantation [37]. However, some seronegative individuals still face complications following organ transplantation and HCMV may play a role.…”

Challenging the Conventional Interpretation of HCMV Seronegativity

“…These may be transient with control by NK cells (as in case 2) or persistent with seroconversion blocked by vIL-10. It is clear that seropositivity is a risk factor for adverse outcomes following renal transplantation [27]. However some seronegative individuals still face complications following organ transplantation and HCMV may play a role.…”