title: Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.
abstract: BACKGROUND
  Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy.
  
  
  METHODS
  Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression.
  
  
  RESULTS
  We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI, .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy.
  
  
  CONCLUSIONS
  This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.
authors.affiliation: Research Department of Infection and Population Health, University College London.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jose
authors.affiliation: Kings College Hospital National Health Service (NHS) Foundation Trust and King's College London School of Medicine.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hamzah
authors.affiliation: Kings College Hospital National Health Service (NHS) Foundation Trust and King's College London School of Medicine.
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Campbell
authors.affiliation: Research Department of Infection and Population Health, University College London.
authors.forename: Teresa
authors.initials: T
authors.lastname: Hill
authors.affiliation: Brighton and Sussex University Hospitals NHS Trust, Brighton.
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.affiliation: The Lothian University Hospitals NHS Trust, Edinburgh.
authors.forename: Clifford
authors.initials: C
authors.lastname: Leen
authors.affiliation: Mortimer Market Centre, University College Medical School.
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.affiliation: Imperial College Healthcare NHS Trust.
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.affiliation: Chelsea and Westminster NHS Foundation Trust.
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.affiliation: St George's Healthcare NHS Trust.
authors.forename: Phillip
authors.initials: P
authors.lastname: Hay
authors.affiliation: Royal Free Hampstead NHS Trust.
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.affiliation: South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Chadwick
authors.affiliation: London School of Hygiene and Tropical Medicine, London.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nitsch
authors.affiliation: Chelsea and Westminster NHS Foundation Trust.
authors.forename: Rachael
authors.initials: R
authors.lastname: Jones
authors.affiliation: Research Department of Infection and Population Health, University College London.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: Kings College Hospital National Health Service (NHS) Foundation Trust and King's College London School of Medicine.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine
keywords: eGFR; eGFR slopes; highly active antiretroviral therapy; kidney; renal function; tenofovir