title: Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial.
abstract: OBJECTIVE
  Tenofovir disoproxil fumarate (TDF) use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by persons with human immunodeficiency virus (HIV) type 1, but limited data are available for risk when used as preexposure prophylaxis (PrEP) for HIV-1 prevention.
  
  
  OBJECTIVE
  To determine whether TDF-based PrEP causes eGFR decline in HIV-1-uninfected adults.
  
  
  METHODS
  A per-protocol safety analysis of changes in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among heterosexual HIV-1-uninfected members of serodiscordant couples in Kenya and Uganda. The trial was conducted from 2008 to 2012.
  
  
  METHODS
  Predefined outcomes of this analysis were mean eGFR change and a 25% or greater eGFR decline from baseline. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation.
  
  
  RESULTS
  Of 4640 participants in the once-daily TDF (n = 1548), FTC-TDF (n = 1545), or placebo (n = 1547) groups, 63% were men. At enrollment, median age was 35 years (range, 18-64 years), and mean eGFR was 130 mL/min/1.73 m². During a median follow-up of 18 months (interquartile range 12-27 months), mean within-group eGFR change from baseline was +0.14 mL/min/1.73 m² for TDF, -0.22 mL/min/1.73 m² for FTC-TDF, and +1.37 mL/min/1.73 m² for placebo, translating into average declines in eGFR attributable to PrEP vs placebo of -1.23 mL/min/1.73 m² (95% CI, -2.06 to -0.40; P = .004) for TDF and -1.59 mL/min/1.73 m² (95% CI, -2.44 to -0.74; P < .001) for FTC-TDF. The difference in mean eGFR between PrEP and placebo appeared by 1 month after randomization, was stable through 12 months, and then appeared to wane thereafter. The respective proportions of persons who developed a confirmed 25% or greater eGFR decline from baseline by 12 and 24 months was 1.3% and 1.8% for TDF and 1.2% and 2.5% for FTC-TDF, and these frequencies were not statistically different from the confirmed decline in the placebo group (0.9% and 1.3% by 12 and 24 months, respectively).
  
  
  CONCLUSIONS
  In this large randomized, placebo-controlled trial among heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36 months, daily oral TDF-based PrEP resulted in a small but nonprogressive decline in eGFR that was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00557245.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle2Division of Disease Control, School of Public Health, Makerere University, Kampala, Uganda.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Mugwanya
authors.affiliation: Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York.
authors.forename: Christina
authors.initials: C
authors.lastname: Wyatt
authors.affiliation: Department of Epidemiology, University of Washington, Seattle4Department of Global Health, University of Washington, Seattle5Department of Medicine, University of Washington, Seattle.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Department of Global Health, University of Washington, Seattle6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.affiliation: Department of Global Health, University of Washington, Seattle7Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Nelly R
authors.initials: NR
authors.lastname: Mugo
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 Global Health, University of Washington, Seattle9Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya.
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Ronald
authors.affiliation: Department of Epidemiology, University of Washington, Seattle4Department of Global Health, University of Washington, Seattle5Department of Medicine, University of Washington, Seattle.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine