Impact of Belatacept and Tacrolimus on Cmv Viral Load Control and Relapse in Moderate and High-risk Cmv Serostatus Kidney Transplant Recipients

W. Magua¹, A. C. Johnson¹, G. M. Karadkhele¹, I. R. Badell¹, P. Vasanth¹, M. G. Lyon III², A. K. Mehta², K. A. Easley³, J. Rickert⁴, C. P. Larsen¹

¹Department of Surgery, Emory University, Atlanta, GA, ²Department of Medicine, Emory University, Atlanta, GA, ³Biostatistics and Bioinformatics, Emory University, Atlanta, GA, ⁴RStudio and R Consortium, San Jose, CA

Meeting: 2021 American Transplant Congress

Abstract number: 791

Keywords: Cytomeglovirus, Immunosuppression, Kidney transplantation, T cells

Topic: Clinical Science » Infectious Disease » Kidney Infectious Non-Polyoma & Non-Viral Hepatitis

Session Information

Session Name: Kidney Infectious Non-Polyoma & Non-Viral Hepatitis

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: We aim to evaluate the impact of belatacept and tacrolimus on CMV viral load control, remission and relapse in CMV high-risk (serostatus, D+/R-) and moderate-risk (D+/R+ or D-/R+) recipients.

*Methods: We included 175 CMV recipients with at least 1 episode of viremia within 1 year after transplantation. We used a multi-state, continuous time homogenous Markov model to evaluate viral load transitions across states: state 1, undetectable or low viral load [0, 500) copies/mL; state 2, moderate viremia [500, 10⁴) copies/mL; and state 3, high viremia (viral load >= 10⁴).

*Results: CMV high-risk belatacept-treated recipients presented an increased risk (HR = 2.06; CI = 1.14, 3.74) of transition from state 1 to 2 and a decreased risk (HR = 0.365; CI = 0.164, 0.812) of transitioning from state 2 to 3 than high-risk tacrolimus-treated recipients. Hence, state 2 emerged as a sticky state for high-risk belatacept-treated recipients. High-risk belatacept-treated recipients were predicted to persist in state 2 for a significantly longer time (128 days, CI =110,145) than high-risk tacrolimus-treated recipients (70.6 days, CI = 47.6, 99.2). Conversely, the high-risk tacrolimus group had greater persistence in state 1 compared to belatacept. In contrast, moderate-risk belatacept-treated recipients showed much better viral load control with a decreased risk of transitioning from state 2 to state 3 (HR 0.307; CI =0.110, 0.852) and with no other significant differences in viral load transition risks and in the short durations in viremic states when compared to moderate-risk tacrolimus-treated recipients.

*Conclusions: High-risk belatacept-treated recipients showed a pattern of protracted viremia with impaired development of protective immunity. High-risk tacrolimus-treated recipients established some level of protective immunity despite blocking signaling in both naïve and memory T cells. Viral control was similar in moderate risk recipients treated with belatacept or tacrolimus. The results suggest that knowledge of viral-specific T cell response remains incomplete and that belatacept should be used with caution in CMV high-risk recipients while further strategies that can improve CMV serostatus matching are considered.

To cite this abstract in AMA style:

Magua W, Johnson AC, Karadkhele GM, Badell IR, Vasanth P, III MGLyon, Mehta AK, Easley KA, Rickert J, Larsen CP. Impact of Belatacept and Tacrolimus on Cmv Viral Load Control and Relapse in Moderate and High-risk Cmv Serostatus Kidney Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-belatacept-and-tacrolimus-on-cmv-viral-load-control-and-relapse-in-moderate-and-high-risk-cmv-serostatus-kidney-transplant-recipients/. Accessed November 21, 2024.

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