Belatacept-related cytomegalovirus infection: Advocacy for tailored immunosuppression based on individual assessment of immune fitness

Belatacept, a fusion protein combining cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the Fc region of human IgG1, is increasingly used as a calcineurin inhibitor-sparing regimen in patients with chronic graft dysfunction. Older kidney transplant recipients, particularly from expanded criteria donors, may be switched to belatacept due to poor renal recovery. However, late-onset cytomegalovirus (CMV) reactivation is increasingly reported with this treatment, especially in older patients with graft dysfunction. This suggests a progressive loss of CMV-specific T cell response, potentially driven by T cell exhaustion. Contributing factors include preexisting T cell dysfunction, increased viral antigen exposure, and interference in the PD-L1/PD-1 pathway by belatacept. mTOR inhibitors have shown efficacy in preventing CMV reactivation by reinvigorating CMV-specific T cells. These findings support combining belatacept with mTOR inhibitors in high-risk CMV-seropositive recipients and emphasize the need for personalized immune assessments to guide immunosuppressive strategies.