Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy vs. prophylaxis

Danniel Zamora; Sayan Dasgupta; Terry Stevens-Ayers; Bradley Edmison; Drew J. Winston; Raymund R. Razonable; Aneesh K. Mehta; G. Marshall Lyon; Michael Boeckh; Nina Singh; David M. Koelle; Ajit P. Limaye

doi:10.1172/jci.insight.180115

Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy vs. prophylaxis

Danniel Zamora,¹ Sayan Dasgupta,² Terry Stevens-Ayers,² Bradley Edmison,² Drew J. Winston,³ Raymund R. Razonable,⁴ Aneesh K. Mehta,⁴ G. Marshall Lyon,⁵ Michael Boeckh,¹ Nina Singh,⁶ David M. Koelle,¹ and Ajit P. Limaye¹

Published August 5, 2024 - More info

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Abstract

Cytomegalovirus (CMV)-specific T-cells, NK cells, and neutralizing antibodies (nAb) were assessed in a randomized trial of CMV prevention with preemptive antiviral therapy (PET) vs. prophylactic antiviral therapy (PRO) in donor seropositive/recipient seronegative (D+R-) liver transplant recipients (LTxR), at 100 days (end of intervention), and at 6 and 12 months post-transplant. The PET group had significantly increased numbers of circulating polyfunctional T-cells, NK cells, and nAb compared to the PRO group at day 100 and several CMV immune parameters remained significantly higher by 12 months post-transplant. Among PET recipients, preceding CMV viremia (vs. no preceding viremia) was associated with significantly higher levels of most CMV immune parameters at day 100. Higher numbers of CMV-specific polyfunctional T-cells and NKG2C⁺ NK cells at day 100 were associated with a decreased incidence of CMV disease in multivariable Cox regression. The strongest associations with protection against CMV disease were with increased numbers of CMV-specific polyfunctional CD4 T-cells, CD3^negCD56^dimCD57^negNKG2C^pos, and CD3^negCD56^dimCD57^posNKG2C^pos NK cells. PET is superior to PRO for CMV disease prevention by allowing low-level CMV replication and associated antigen exposure that is promptly controlled by antiviral therapy and facilitates enhanced CMV protective immunity in D+R- LTxR.

Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy vs. prophylaxis

Danniel Zamora,¹ Sayan Dasgupta,² Terry Stevens-Ayers,² Bradley Edmison,² Drew J. Winston,³ Raymund R. Razonable,⁴ Aneesh K. Mehta,⁴ G. Marshall Lyon,⁵ Michael Boeckh,¹ Nina Singh,⁶ David M. Koelle,¹ and Ajit P. Limaye¹

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Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy vs. prophylaxis

Danniel Zamora,1 Sayan Dasgupta,2 Terry Stevens-Ayers,2 Bradley Edmison,2 Drew J. Winston,3 Raymund R. Razonable,4 Aneesh K. Mehta,4 G. Marshall Lyon,5 Michael Boeckh,1 Nina Singh,6 David M. Koelle,1 and Ajit P. Limaye1

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Danniel Zamora,¹ Sayan Dasgupta,² Terry Stevens-Ayers,² Bradley Edmison,² Drew J. Winston,³ Raymund R. Razonable,⁴ Aneesh K. Mehta,⁴ G. Marshall Lyon,⁵ Michael Boeckh,¹ Nina Singh,⁶ David M. Koelle,¹ and Ajit P. Limaye¹