title: Low Risk of Proximal Tubular Dysfunction Associated With Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women.
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.
authors.affiliation: Department of Epidemiology Department of Global Health Division of Disease Control, School of Public Health, Makerere University, Kampala, Uganda.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mugwanya
authors.affiliation: Department of Epidemiology Department of Global Health Department of Medicine, University of Washington.
authors.forename: Jared
authors.initials: J
authors.lastname: Baeten
authors.affiliation: Department of Epidemiology Department of Global Health Department of Medicine, University of Washington.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Department of Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.affiliation: Department of Medicine, Division of Nephrology.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nickolas
authors.affiliation: Department of Global Health Kenya Medical Research Institute.
authors.forename: Nelly
authors.initials: N
authors.lastname: Mugo
authors.affiliation: Department of Medicine, Division of Liver Diseases.
authors.forename: Andrea
authors.initials: A
authors.lastname: Branch
authors.affiliation: Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jordan
authors.initials: J
authors.lastname: Tappero
authors.affiliation: Department of Obstetrics and Gynecology, University of Nairobi, Kenya.
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Ronald
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center.
authors.forename: Michael
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Christina
authors.initials: C
authors.lastname: Wyatt
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018890:Chemoprevention / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D051437:Renal Insufficiency / Q000139:chemically induced*; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects*; D016482:Urinalysis; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D000068698:Tenofovir
keywords: PrEP; TDF nephrotoxicity; TDF toxicity; proximal tubular dysfunction