Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Abstract

Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analysed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: -12.0±4.2 mL·min -1 ·1.73m -2 , P=0.005). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex.

Current characteristics and outcomes of Cytomegalovirus Reactivation in kidney transplant seropositive recipients in the era of prophylaxis treatment. Lesson from single Moroccan center experience

“…Considering other infections than CMV, the occurrence of intercurrent infection was more frequent in those patients with symptomatic reactivation 6 (75%) vs. 5 (22.7%), P= 0.028. Our finding agreed with Blazquez-Navarro et al [54] who revealed a strong association between the reactivation of cytomegalovirus and BK virus regardless of the level of viral load measurement.…”

“…The rate was found higher than in the previously two published studies [47,53] with 34% and 30%, respectively. Similarly, in another report, the high level of CMV viraemia was positively associated with acute rejection [OR= 3.27,95%IC = 1.08-9.4, P= 0.039] [54]. But in our study, the number of events was too small to assess a peak viral load effect on the occurrence of rejection episode.…”

Impaired Humoral and Cellular Immunity after SARS-CoV2 BNT162b2 (Tozinameran) Prime-Boost Vaccination in Kidney Transplant Recipients

“…This has been comprehensively documented e.g. for cytomegalo-, Epstein-Barr-and BK-virus infection (2), commonly affecting renal transplant recipients with potential implications for allograft function. A growing body of evidence indicates that both patient groups show considerably increased mortality after SARS-CoV2 infection (3)(4)(5)(6), arguing in favor of their prioritization in coronavirus disease 2019 (COVID-19) vaccination programs.…”

Assessing Anti-HCMV Cell Mediated Immune Responses in Transplant Recipients and Healthy Controls Using a Novel Functional Assay

“…Recent data suggest that the prophylactic strategy requires less intensive patient monitoring in SOT, and is associated with lower viraemia and a lower risk of HCMV reactivation/reinfection compared to pre-emptive treatment (Griffiths, 2019 ). However prophylactic treatment also leads to an increased risk of late-onset disease due to poorer cell-mediated immunity in D+R– transplants (Limaye et al, 2019 ); and poorer patient outcomes, including reduced kidney function and increased risk of graft rejection (Blazquez-Navarro et al, 2019 ). There is conflicting evidence as to whether prophylaxis significantly increases the risk of drug resistance (Hakki and Chou, 2011 ; López-Aladid et al, 2017 ).…”