Correlation Between Tenofovir Drug Levels and the Renal Biomarkers RBP-4 and ß2M in the ION-4 Study Cohort.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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+).<h4>Results</h4>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.<h4>Conclusions</h4>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.
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https://hdl.handle.net/10161/26434Published Version (Please cite this version)
10.1093/ofid/ofy273Publication Info
Chan, Austin; Park, Lawrence; Collins, Lauren F; Cooper, Curtis; Saag, Michael; Dieterich,
Douglas; ... Naggie, Susanna (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). pp. 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.
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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 Duk
Lawrence P Park
Associate Professor in Medicine
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