Low Risk of Proximal Tubular Dysfunction Associated with Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women

Kenneth Mugwanya, Jared Baeten, Connie Celum, Deborah Donnell, Thomas Nickolas, Nelly Mugo, Andrea Branch, Jordan Tappero, James Kiarie, Allan Ronald, Michael Yin, Christina Wyatt, Robert W. Coombs, Lisa Frenkel, Craig W. Hendrix, Jairam R. Lingappa, M. Juliana McElrath, Eldoret Kenya, Kenneth H. Fife, Edwin WereElioda Tumwesigye, Patrick Ndase, Elly Katabira, Elizabeth Bukusi, Craig R. Cohen, Jonathan Wangisi, James D. Campbell, Jordan W. Tappero, Carey Farquhar, Grace John-Stewart, Nelly R. Mugo

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Objective.Tenofovir disoproxil fumarate (TDF) is associated with proximal tubular dysfunction (tubulopathy) when used in the treatment of human immunodeficiency virus (HIV) infection. We evaluated whether TDF causes tubulopathy when used as HIV preexposure prophylaxis (PrEP) and whether tubulopathy predicts clinically relevant decline (≥25%) in the estimated glomerular filtration rate (eGFR). Methods.A subgroup analysis of the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF, alone or with emtricitabine (FTC), in HIV-uninfected African men and women (Clinicaltrials.gov NCT00557245). Tubulopathy was assessed in concurrently obtained urine and serum samples at the 24-month or last on-treatment visit, predefined as ≥2 of the following: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate, and uric acid excretion. Results.Of 1549 persons studied (776 receiving FTC-TDF, 773 receiving placebo), 64% were male, and the median age was 37 years. Over a median 24 months of study-drug exposure, the frequency of tubulopathy was 1.7% for FTC-TDF versus 1.3% for placebo (odds ratio, 1.30; 95% confidence interval,. 52-3.33; P =. 68); Tubulopathy occurred in 2 of 52 persons (3.8%) with versus 3 of 208 (1.4%) without ≥25% eGFR decline (adjusted odds ratio, 1.39;. 10-14.0; P >. 99). Conclusions.Daily oral FTC-TDF PrEP was not significantly associated with tubulopathy over the course of 24 months, nor did tubulopathy predict clinically relevant eGFR decline.

Original languageEnglish (US)
Pages (from-to)1050-1057
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number7
DOIs
StatePublished - Oct 1 2016

Keywords

  • PrEP
  • TDF nephrotoxicity
  • TDF toxicity
  • proximal tubular dysfunction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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