Reversibility of Glomerular Renal Function Decline in HIV-Uninfected Men and Women Discontinuing Emtricitabine-Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis

J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):374-80. doi: 10.1097/QAI.0000000000000868.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / adverse effects*
  • Creatinine / blood
  • Drug Administration Schedule
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / adverse effects*
  • Female
  • Glomerular Filtration Rate / drug effects*
  • HIV
  • HIV Infections / prevention & control
  • Humans
  • Kidney Diseases / chemically induced*
  • Male
  • Middle Aged
  • Pre-Exposure Prophylaxis*
  • Young Adult


  • Anti-HIV Agents
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
  • Creatinine