Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec;24(6):e13983.
doi: 10.1111/tid.13983. Epub 2022 Nov 14.

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

Wairimu Magua  1 , Aileen C Johnson  1 , Geeta M Karadkhele  1 , Idelberto R Badell  1 , Payaswini Vasanth  1 , Aneesh K Mehta  2 , Kirk A Easley  3 , Kenneth A Newell  1 , Joseph B Rickert  4   5 , Christian P Larsen  1
Affiliations

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

Wairimu Magua et al. Transpl Infect Dis. 2022 Dec.

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.

Keywords: CMV bidirectional viral load state transitions; CMV control; CMV high-risk; CMV management strategies; CMV moderate-risk; CMV relapse; CMV serostatus risk; CMV viral infection and infectious agents; CMV viral load dynamics; CMV viral load volatility; Markov multistate; belatacept; clinical research/practice; cytomegalovirus; immunosuppression/immune modulation; immunosuppressive regimens-maintenance; infectious disease; kidney (allograft) function/disfunction; kidney transplant; length of stay in viral load state; tacrolimus; viral load trajectory; viremia.

PubMed Disclaimer

Conflict of interest statement

All authors in this manuscript declared no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart illustrating the selection of the study cohort. †Recipients who remained negative for viremia consistently throughout the study period. ‡Recipients who experienced at least one episode of viremia within 1 year after transplant
FIGURE 2
FIGURE 2
Area under the cytomegalovirus (CMV) viral curves (AUC) as a summary measure within CMV risk status (A moderate risk, B high risk) and by immunosuppression protocol using nonparametric Mann–Whitney U test
FIGURE 3
FIGURE 3
Estimated probability of remaining in a viral load state by immunosuppression protocol within cytomegalovirus (CMV) serostatus risk groups after the complete evolution of the Markov process
FIGURE 4
FIGURE 4
Estimated total length of stay (days) over the entire evolution of the Markov process in each state by immunosuppression protocol within recipient cytomegalovirus (CMV) risk status
See this image and copyright information in PMC

References

    1. López‐Oliva MO, Flores J, Madero R, et al. Cytomegalovirus infection after kidney transplantation and long‐term graft loss. Nefrologia. 2017;37(5):515‐525. 10.1016/j.nefro.2016.11.018 - DOI - PubMed
    1. Kotton CN, Kumar D, Caliendo AM, et al. The third international consensus guidelines on the management of cytomegalovirus in solid‐organ transplantation. Transplantation. 2018;102(6):900‐931. 10.1097/TP.0000000000002191 - DOI - PubMed
    1. Xin W, Hui Y, Xiaodong Z, Xiangli C, Shihui W, Lihong L. Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in renal transplantation: a systematic review and meta‐analysis. J Pharm Pharm Sci. 2017;20(0):168‐183. doi: 10.18433/J3805B - DOI - PubMed
    1. Heldenbrand S, Li C, Cross RP, et al. Multicenter evaluation of efficacy and safety of low‐dose versus high‐dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients. Transpl Infect Dis. 2016;18(6):904‐912. 10.1111/tid.12609 - DOI - PubMed
    1. McBride JM, Sheinson D, Jiang J, et al. Correlation of cytomegalovirus (CMV) disease severity and mortality with CMV viral burden in CMV‐seropositive donor and CMV‐seronegative solid organ transplant recipients. Open Forum Infect Dis. 2019;6(2):ofz003. 10.1093/ofid/ofz003 - DOI - PMC - PubMed