Impact of belatacept and tacrolimus on cytomegalovirus viral load control and relapse in moderate and high‐risk cytomegalovirus serostatus kidney transplant recipients

Abstract

Background Belatacept improves long‐term graft survival, but control of some primary viral infections may be impaired. We evaluated the impact of belatacept and tacrolimus on cytomegalovirus (CMV) viral control, remission and relapse in CMV high‐risk and moderate‐risk recipients. Methods Using a multistate Markov model, we evaluated viral load state transitions of 173 kidney transplant recipients with at least one episode of viremia within 1 year after transplant: state 1, undetectable/low viral load; state 2, moderate viremia; and state 3, severe viremia. Results Among high‐risk recipients, belatacept‐treated recipients exhibited a significantly higher probability of entering moderate viremia (.36; 95% CI = .31, .41) than tacrolimus‐treated recipients (.20; 95% CI = .13, .29). The expected number of days in viremic states differed. High‐risk belatacept‐treated recipients persisted in moderate viremia for significantly longer (128 days, 95% CI = 110, 146) than did tacrolimus‐treated recipients (70.0 days, 95% CI = 45.2, 100) and showed a trend of shorter duration in low/undetectable viral load state (172 days, 95% CI = 148, 195) than did tacrolimus‐treated recipients (239 days, 95% CI = 195, 277). Moderate‐risk recipients showed better viral load control and with no differences by immunosuppression. Conclusion High‐risk belatacept‐treated recipients showed defects in sustaining viral control relative to tacrolimus‐treated recipients. Avoidance of initial use belatacept in high‐risk recipients or development of modified management protocols should be considered.

The Best Method for CMV Prevention in High-risk Kidney Transplant Recipients? Either, per National Norwegian Transplant Database: Commentary on Blom et al, Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management

“…5,6 Costs for each type of prevention are significant, although both approaches are usually found to be cost-effective compared with no prevention, and should be evaluated in individual transplant programs and regions. Whether specific populations (ie, D+R− on belatacept 7 ) might benefit from one method of prevention over another merit further investigation, as does selecting the best prophylactic drug, given the recent emergence of multiple CMV-specific antiviral agents that may be useful for prophylaxis (ie, letermovir, maribavir). 8 This work by Blom et al 1 highlights the overall high rates of CMV infection even with the current best methods of prevention in the D+R− population (40% with prophylaxis, 64% with preemptive therapy), similar to what was seen with 100 d of prophylaxis in the IMPACT trial of D+R− kidney transplant recipients where 39% developed CMV disease (albeit with less routine monitoring than in this Norwegian work), although almost twice that seen with 200 d of prophylaxis in that trial at 21%.…”

“…5,6 Costs for each type of prevention are significant, although both approaches are usually found to be cost-effective compared with no prevention, and should be evaluated in individual transplant programs and regions. Whether specific populations (ie, D+R− on belatacept 7 ) might benefit from one method of prevention over another merit further investigation, as does selecting the best prophylactic drug, given the recent emergence of multiple CMV-specific antiviral agents that may be useful for prophylaxis (ie, letermovir, maribavir). 8…”