Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria.
The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC.
A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE.
In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m2 (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: −7% to 20%).
PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.
*Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, CA;
†Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA;
‡Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA;
§Department of Biostatistics and Epidemiology, University of California, San Francisco, San Francisco, CA;
‖Gladstone Institutes, University of California, San Francisco, CA;
¶Bridge HIV, San Francisco Department of Public Health, San Francisco, CA;
#Department of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, CA;
**Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH;
††Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY;
‡‡Department of Medicine, Section of Nephrology, Yale University, New Haven, CT;
§§Program of Applied Translational Research, Yale University, New Haven, CT; and
‖‖Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA.
Correspondence to: Vasantha Jotwani, MD, 4150 Clement Street, 111A1, San Francisco, CA 94121, (e-mail: Vasantha.Jotwani@ucsf.edu).
Supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant 1K23DK109868 and by the University of California, San Francisco, Center For AIDS Research Mentored Science Award to Dr. Jotwani; by the National Institute on Aging grant 2R01AG034853 to Dr. Shlipak and Dr. Parikh; and by the National Institute of Allergy and Infectious Diseases grant 2R01AI098472 to Dr. Gandhi.
The authors have no funding or conflicts of interest to disclose.
Gilead Sciences donated tenofovir disoproxil fumarate and emtricitabine for the original studies, but provided no other financial support and did not contribute to data interpretation or manuscript development. D.V.G. has received fees from Gilead Sciences. R.M.G. has received research funding from ViiV Healthcare for a competing PrEP product. The remaining authors have no funding or conflicts of interest to disclose.
V.J., R.S., D.V.G., M.M., P.D., A.L., M.G., S.G.C., C.R.P., R.M.G., and M.G.S. contributed substantially to study design, data interpretation, and manuscript preparation. R.M.G. is the PI of iPrEx and iPrEx-OLE. M.M., P.D., D.V.G., A.L., M.G., M.B., S.G.C., C.R.P., V.J., and M.G.S. all contributed substantially to data collection and measurements. R.S. and D.V.G. performed all statistical analyses. V.J. and M.G.S. drafted the initial manuscript, with all authors contributing substantially to its development.
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Received December 07, 2017
Accepted January 25, 2018