Work

Impact of Direct‐Acting Antiviral Therapy on Tacrolimus Pharmacokinetics in Hepatitis C Virus Nucleic Acid Testing‐Positive Transplant Recipients

Year: 2025

Type: article

Abstract: Purpose: Direct‐acting antiviral agents (DAAs) against hepatitis C virus (HCV) such as sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) are effective in treating recipients of organs infected with HCV. The objective of this project is to identify changes in tacrolimus pharmacokinetics throughout DAA therapy in recipients of abdominal transplants from nucleic acid testing‐positive (NAT+) donors. Methods: Adult kidney or liver transplant recipients transplanted between 4/22/2019 and 6/23/2022 were included. Recipients of HCV NAT+ organs were treated with DAAs based on institutional protocol and insurance preference. Recipients of HCV NAT− organs from donors who fit Public Health Service (PHS) risk criteria for HCV transmission were included in the comparator group. Tacrolimus doses and concentrations were collected at DAA initiation and cessation and at the time of sustained virologic response assessment at 12 weeks after treatment completion (SVR12); these time points were matched in the NAT− control group. The primary outcome was difference in concentration‐to‐dose ratio (C/D) change (ΔC/D) over time between NAT+ and NAT− organ recipients. Results: At DAA initiation, NAT+ organ recipients required a lower tacrolimus dose to reach goal than NAT− organ recipients (ΔC/D NAT+ = −0.41, ΔC/D NAT− 0.60, p = 0.01); however, a known tacrolimus interaction with fluconazole—administered to liver transplant recipients at high risk for invasive fungal infection (IFI)—represents a significant confounding factor. No differences in average C/D ratio between NAT+ and NAT− organ recipients were identified at any time point. Conclusion: These results do not support empiric dose adjustments based on donor HCV NAT status or antiviral therapy.

Source: Journal of Clinical Pharmacy and Therapeutics

DOI: 10.1155/jcpt/5727663

Authors: Jared Walz, Glen Leverson, Lily Stalter, John Rice, David Al-Adra, Joshua J. Wiegel

Institutions: University of Wisconsin–Madison, UW Health University Hospital

Language: English

Topic: Hepatitis C virus research

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,700