The effect of anti‐thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis

Basso, Geovana; Felipe, Cláudia Rosso; Cristelli, Marina Pontello; Siliano, Juliana Mansur; Viana, Laila Almeida; Brigido, Alexandra Nicolau Ferreira; Martins, Suelen Bianca Stopa; Santos, Daniel Wagner de Castro Lima; Aguiar, Wilson; Tedesco‐Silva, Hélio; Medina-Pestana, José

doi:10.1111/tid.12919

Cited by 7 publications

(4 citation statements)

References 32 publications

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Section: Discussionmentioning

confidence: 99%

“…mTORi limit CMV viral replication using several complex and integrated mechanisms, including enhancement of innate immunity, inhibition of viral mRNA translation, and expansion of the number and quality of antigen‐specific CD8+ memory T cells . Patients treated with EVR show lower viral load compared with those treated with mycophenolate, even receiving r‐ATG inducting therapy . Furthermore, patients treated with EVR show a significant increase in CMV‐specific effector‐type CD8 and CD4 T‐cell counts compared with patients receiving either cyclosporine or mycophenolate .…”

Section: Discussionmentioning

confidence: 99%

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Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

Cristelli

Felipe

Prizmic

et al. 2019

Clinical Transplantation

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Objectives To describe the incidence of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving an mTOR‐inhibitor‐containing immunosuppressive regimen without prophylactic CMV treatment. Methods This single‐center retrospective cohort analysis included all de novo kidney transplant recipients (09/15/2015‐07/31/2017) receiving 3 mg/kg single dose of rabbit antithymocyte globulin induction, tacrolimus, everolimus, and prednisone. Preemptive therapy was initiated only in patients deemed at higher risk for CMV infection: (a) D+/R− CMV patients; (b) after treatment for acute rejection (ARt); and (c) after everolimus discontinuation (EVRd). Results Of 230 patients, there were no episodes of CMV disease among 217 (94%) without criteria to initiate preemptive therapy. Of 77 (33.5%) patients initiating preemptive therapy, 13 were D+/R−, 30 were ARt, and 34 were EVRd. The overall incidence of first CMV infection/disease was 6% (46.1% in D+/R−, 13.3% ARt [all patients had also discontinued everolimus], and 11.8% after early [<90 days] EVRd). The incidence of biopsy‐proven acute rejection was 5.6%, and median glomerular filtration rate at month 12 was 47 mL/min/1.73m2. One‐year patient and death‐censored graft survivals were 97.4% and 98.1%. Conclusion This study suggests that everolimus‐containing immunosuppressive regimen reduces the need for preventive strategies for CMV infection in the majority of kidney transplant recipients, reducing antiviral drug‐associated toxicities and healthcare‐related expenditures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

Cristelli

Felipe

Prizmic

et al. 2019

Clinical Transplantation

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“…7 Incidence of viremia, viral load peaks, and AUC have frequently been used in traditional statistical methods to characterize the burden of CMV viral load and predict CMV-related outcomes. 5,7,16 Although these summary measures are relevant, they remain incomplete as they do not capture viral load dynamics, such as the frequency of change between viral load levels or states over time needed to capture viral load volatility. 17 load monitoring, similar to our study, and provide valid inference for such data.…”

Section: Introductionmentioning

confidence: 99%

“…When considering CMV serostatus, we previously reported that high‐risk belatacept‐treated recipients (donor/recipient serostatus pair: D+/R−) showed a higher cumulative incidence of CMV viremia, higher area under the viral load curves (AUC), and a trend of high risk of graft loss than tacrolimus‐treated recipients 7 . Incidence of viremia, viral load peaks, and AUC have frequently been used in traditional statistical methods to characterize the burden of CMV viral load and predict CMV‐related outcomes 5,7,16 . Although these summary measures are relevant, they remain incomplete as they do not capture viral load dynamics, such as the frequency of change between viral load levels or states over time needed to capture viral load volatility 17 …”

Section: Introductionmentioning

confidence: 99%

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

Magua

Johnson

Karadkhele

et al. 2022

Transplant Infectious Dis

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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.

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Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Webster

Lee

Chapman

et al. 2006

Cochrane Database of Systematic Reviews

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TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed.

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The effect of anti‐thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis

Abstract: These data suggest that mTOR inhibitors reduce the incidence of CMV infection by limiting CMV viral replication.

Cited by 7 publications

References 32 publications

Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

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

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

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