Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals

Vasantha Jotwani, Rebecca Scherzer, David V. Glidden, Megha Mehrotra, Patricia Defechereux, Albert Liu, Monica Gandhi, Michael Bennett, Steven G. Coca, Chirag R. Parikh, Robert M. Grant, Michael G. Shlipak

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: 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: a1-microglobulin (a1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. Setting: 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. Methods: 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. Results: In iPrEx, there were no significant differences in urine a1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine a1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable a1m 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%). Conclusion: PrEP with TDF/FTC was associated with a statistically significant rise in urine a1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

Original languageEnglish (US)
Pages (from-to)169-174
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume78
Issue number2
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Keywords

  • Alpha-1 microglobulin
  • HIV prevention
  • Kidney injury
  • Nephrotoxicity
  • Pre-exposure prophylaxis (PrEP)
  • Tubular dysfunction
  • Urine biomarkers

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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