title: Reversibility of Glomerular Renal Function Decline in HIV-Uninfected Men and Women Discontinuing Emtricitabine-Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis.
abstract: BACKGROUND
  Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis (PrEP) use is associated with a small but statistically significant decline in estimated glomerular filtration rate (eGFR). We investigated the reversibility of eGFR decline among HIV-uninfected adults discontinuing PrEP.
  
  
  METHODS
  Data were from the Partners PrEP Study, a randomized trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African HIV-uninfected men and women with baseline creatinine clearance ≥60 mL/min. Serum creatinine was measured quarterly while on-study medication and at month 1 and 2 after discontinuation. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation.
  
  
  RESULTS
  A total of 3924 individuals had a poststudy drug serum creatinine measurement after the scheduled drug discontinuation (1271 for TDF, 1308 for FTC-TDF, and 1345 for placebo); 65% were men, median age was 35 (range 18-64) years. Median time on study drug was 33 (interquartile range 25-36) months overall, and 36 months (interquartile range 30-36) for TDF and FTC-TDF. Mean eGFR at the last on-treatment visit was 129 mL·min·1.73 m for TDF and 128 mL·min·1.73 m for FTC-TDF versus 131 mL·min·1.73 m for placebo (2-3 mL·min·1.73 m mean decline for PrEP versus placebo, P ≤ 0.01), and this difference reversed by 4 weeks after drug discontinuation (mean eGFR at the first postdrug visit: 130 mL·min 1.73 m in all groups). More than 96% of participants had a confirmed >75% eGFR rebound to baseline level by 8 weeks after drug discontinuation, with similar proportions across treatment groups.
  
  
  CONCLUSIONS
  In this large, placebo-controlled study of TDF-based PrEP, the small reduction in mean eGFR associated with PrEP reversed within weeks after discontinuation.
authors.affiliation: *Department of Epidemiology, University of Washington, Seattle, WA;†Division of Disease Control, School of Public Health, Makerere University, Kampala, Uganda;‡Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY;Departments of §Global Health;‖Medicine, University of Washington, Seattle, WA;¶Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;#Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya; and**Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Mugwanya
authors.forename: Christina
authors.initials: C
authors.lastname: Wyatt
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.forename: Allan
authors.initials: A
authors.lastname: Ronald
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006678:HIV; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D065129:Pre-Exposure Prophylaxis; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D003404:Creatinine