Correlation Between Tenofovir Drug Levels and the Renal Biomarkers RBP-4 and ß2M in the ION-4 Study Cohort.

Abstract

Background

Concomitant dosing of ledipasvir (LDV) and tenofovir disoproxil fumarate (TDF) results in an increased tenofovir (TFV) area under the curve (AUC). The aim of this study was to examine whether there was a correlation between the renal biomarkers retinol binding protein-4 (RBP-4) and β2 microglobulin (β2M) and tenofovir AUC.

Methods

The ION-4 trial enrolled HIV/hepatitis C virus-coinfected patients on nonpharmacologically boosted antiretroviral regimens with TDF-containing backbones. We assessed for a correlation between tenofovir AUC and urinary biomarkers and also for changes in serologic biomarkers with respect to clinically relevant changes in renal function (creatinine clearance decrease >25%, change in creatinine >0.2 mg/dL, change in proteinuria from negative/trace to ≥1+).

Results

Three hundred thirty-five patients were enrolled in the ION-4 study; their demographic characteristics have been previously described. Both RBP-4 and β2M exhibited positive correlations with tenofovir AUC. Baseline and study levels of RBP-4 and β2M were higher for patients with increases in urine proteinuria and an absolute creatinine increase.

Conclusions

TFV exposure is associated with increased proximal tubule urine biomarkers in participants on ledipasvir/sofosbuvir and nonpharmacologically boosted TDF-based antiretroviral regimens. Baseline proximal tubule biomarkers may predict nephrotoxicity risk if events are prevalent. Further studies assessing the predictive role of these urine biomarkers may help guide medical decision-making and risk/benefit assessments in patients with risk factors for renal dysfunction.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/ofid/ofy273

Publication Info

Chan, Austin, Lawrence Park, Lauren F Collins, Curtis Cooper, Michael Saag, Douglas Dieterich, Mark Sulkowski, Susanna Naggie, et al. (2019). Correlation Between Tenofovir Drug Levels and the Renal Biomarkers RBP-4 and ß2M in the ION-4 Study Cohort. Open forum infectious diseases, 6(1). p. ofy273. 10.1093/ofid/ofy273 Retrieved from https://hdl.handle.net/10161/26434.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Park

Lawrence P Park

Associate Professor in Medicine
Naggie

Susanna Naggie

Professor of Medicine

Dr. Susanna Naggie completed her undergraduate degrees in chemical engineering and biochemistry at the University of Maryland, College Park, and her medical education at Johns Hopkins School of Medicine. She conducted her internal medicine and infectious diseases fellowship training at Duke University Medical Center, where she also served as Chief Resident. She joined the faculty in the Duke School of Medicine in 2009. She is a Professor of Medicine and currently holds appointments at the Duke University School of Medicine, at the Duke Clinical Research Institute, and at the Durham Veterans Affairs Medical Center. Dr. Naggie is a clinical investigator with a focus in clinical trials in infectious diseases and translational research in HIV and liver disease. She is a standing member of the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents and the CDC/NIH/IDSA-HIVMA Opportunistic Infections Guideline. She is the Vice Dean for Clinical and Translational Research and Director for the Duke Clinical and Translational Sciences Institute.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.