Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women

William R. Zhang, Rebecca Scherzer, Michelle M. Estrella, Simon B. Ascher, Anthony Muiru, Vasantha Jotwani, Carl Grunfeld, Chirag R. Parikh, Deborah Gustafson, Seble Kassaye, Anjali Sharma, Mardge Cohen, Phyllis C. Tien, Derek K. Ng, Frank J. Palella, Mallory D. Witt, Ken Ho, Michael G. Shlipak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Urinary biomarkers of kidney injury may have potential to identify subclinical injury attributable to tenofovir disoproxil fumarate (TDF) toxicity.Design:This observational study included 198 HIV-infected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, who initiated TDF between 2009 and 2015 and had urine samples collected at baseline before and after TDF initiation.Methods:We used linear mixed-effects models controlling for urine creatinine and time on TDF to evaluate the effects of TDF initiation on changes in 14 urinary biomarkers.Results:Within 1 year after TDF initiation, concentrations of trefoil factor 3 [+78%; 95% confidence interval (CI) +38%, +129%), alpha-1 microglobulin (1m) (+32%; 95% CI +13%, +55%), clusterin (+21%; 95% CI +6%, +38%), uromodulin (+19%; 95% CI +4%, +36%), and kidney injury molecule-1 (KIM-1) (+13%; 95% CI +1%, +26%) significantly increased, whereas interleukin-18 (IL-18) significantly decreased (-13%, 95% CI -7%, -25%). Subsequent to the first year of TDF use, biomarker concentrations stabilized, and these changes were not statistically significant. When stratifying by baseline viremia (HIV-1 RNA < vs. ≥80copies/ml), concentration changes for most biomarkers during the first year of TDF use were greater among aviremic vs. viremic participants, with significant differences in 1m (+80 vs. +22%), KIM-1 (+43 vs. +10%), beta-2 microglobulin (+83 vs. -10%), YKL-40 (+33 vs. -5%), and IL-18 (+20 vs. -27%).Conclusions:TDF initiation was associated with substantial changes in urinary biomarkers of kidney injury within the first year of use, particularly among aviremic participants. A urinary biomarker panel may be a clinically useful tool to detect and monitor the heterogeneous effects of TDF on the kidney.

Original languageEnglish (US)
Pages (from-to)723-733
Number of pages11
JournalAIDS
Volume33
Issue number4
DOIs
StatePublished - Mar 15 2019

Funding

Data in this manuscript were collected by the Women’s Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Mirjam-Colette Kempf and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adi-mora), U01-AI-103390; Connie Wofsy Women’s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I – WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women’s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA), and P30-AI-050410 (UNC CFAR). Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels, Oto Martinez-Maza), U01-AI35040; Harbor-University of California, Los Angeles (Mallory Witt), UL1-TR001881; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D’Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http://aidscohortstudy.org/. M.G.S. is supported by the NIH/NIA (5R01AG034853). W.R.H. is supported by the NIH/NCATS (TL1TR001871). M.G.S. is a Scientific Advisor and holds stock options in the following companies: TAI Diagnostics and Cricket Health, Inc. For the remaining authors, no disclosures were declared. There are no conflicts of interest.

Keywords

  • HIV
  • biomarkers
  • kidney
  • nephrotoxicity
  • tenofovir disproxil fumarate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women'. Together they form a unique fingerprint.

Cite this