The Use of Sofosbuvir (SOF)-Containing Direct Antiviral Agents (DAA)-Based Regimens Requires Increase in Tacrolimus (Tac) Doses in Kidney Transplant (KT) Recipients with Hepatitis C Virus (HCV) Infection.
1Nephrology, Hospital Universitario “12 de Octubre”, Madrid, Spain
2Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Madrid, Spain
3Gastroenterology, Hospital Universitario “12 de Octubre”, Madrid, Spain
4Biochemistry, Hospital Universitario “12 de Octubre”, Madrid, Spain.
Meeting: 2016 American Transplant Congress
Abstract number: 73
Keywords: Calcineurin, Hepatitis C, Kidney transplantation
Session Information
Session Name: Concurrent Session: SOT: HIV, HBV, & HCV
Session Type: Concurrent Session
Date: Sunday, June 12, 2016
Session Time: 2:30pm-4:00pm
Presentation Time: 3:18pm-3:30pm
Location: Room 313
Background: The use of SOF-containing regimens based on NS5A inhibitors has not been shown interactions with Tac in liver transplant.Specific data on KT recipients are still lacking.
Methods: We prospectively analyzed all the KT recipients that received SOF-containing DAA-based therapy in our center between November 2014-November 2015.The primary end-point was sustained virologic response at 12 weeks after end of treatment (EOT) (SVR12).Therapeutic drug monitoring (TDM) for Tac and mofetil mycophenolate (MMF) was performed in whole blood samples at baseline and at weeks 2, 4, 8, 12, 24.Dose adjustments were made as required while on therapy to maintain levels of immunosuppressive drugs within pre-treatment ranges.
Results: We included 33 patients (mean age: 55.3 ± 10.3 y).Immunosuppression included Tac (100.0%), MMF (75.8%), prednisone (72.7%) and everolimus (6.1%).The DAA combinations used were SOF plus ledipasvir (90.9% [n= 30]) or daclatasvir (9.1% [n= 3]). At the time of analysis 14 patients (42.4%) had completed the entire course.The rates of undetectable HCV-RNA at EOT and SVR12 were 100.0% (14/14) and 100.0% (11/11), respectively.There were no significant differences in Tac (p= 0.911) or MMF levels (p= 0.785) between baseline and EOT
|
Variable (mean ± SD)
|
Baseline | W1 | W4 | W12 | W24 |
| Tac levels (ng/mL) | 7.8 ± 2.2 | 7.9 ± 2.6 | 6.1 ± 1.6 | 7.3 ± 1.9 | 7.1 ± 1.9 |
| MMF levels (ng/mL) | 1.8 ± 1.5 | 2.1 ± 2.4 | 2.7 ± 1.8 | 2.7 ± 1.8 | 1.9 ± 1.3 |
. However, Tac doses had to be increased in 92.8% (13/14) of patients by a median of 66.0%. Mean Tac daily doses at baseline and EOT were 2.6 ± 2.0 and 3.4 ± 1.4 mg, respectively (P<0.001). There were no episodes of acute rejection or other relevant adverse events.
Conclusion: The use of SOF-containing regimens in KT recipients requires close TDM of Tac. The underlying mechanism might be related to improvement in hepatic function and Tac clearance rather than to direct drug-to-drug interaction.
CITATION INFORMATION: Polanco Fernandez N, García Santiago A, Fernández Ruiz M, Muñoz R, Alvarez Vazquez C, Hernandez A, Mercado V, González Monte E, Fernández I, Aguado J, Praga M, Andres A. The Use of Sofosbuvir (SOF)-Containing Direct Antiviral Agents (DAA)-Based Regimens Requires Increase in Tacrolimus (Tac) Doses in Kidney Transplant (KT) Recipients with Hepatitis C Virus (HCV) Infection. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Fernandez NPolanco, Santiago AGarcía, Ruiz MFernández, Muñoz R, Vazquez CAlvarez, Hernandez A, Mercado V, Monte EGonzález, Fernández I, Aguado J, Praga M, Andres A. The Use of Sofosbuvir (SOF)-Containing Direct Antiviral Agents (DAA)-Based Regimens Requires Increase in Tacrolimus (Tac) Doses in Kidney Transplant (KT) Recipients with Hepatitis C Virus (HCV) Infection. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/the-use-of-sofosbuvir-sof-containing-direct-antiviral-agents-daa-based-regimens-requires-increase-in-tacrolimus-tac-doses-in-kidney-transplant-kt-recipients-with-hepatitis-c-virus-hcv-infect/. Accessed May 21, 2025.« Back to 2016 American Transplant Congress