title: Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study.
abstract: BACKGROUND
  A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort.
  
  
  METHODS
  We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model.
  
  
  RESULTS
  Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR] = 2.34 [95% CI 1.24-4.42]), higher baseline cGFR (HR = 1.03 [95% CI 1.02-1.04] by 10 ml/min), TDF use (HR = 1.84 [95% CI 1.35-2.51]) and boosted protease inhibitor use (HR = 1.71 [95% CI 1.30-2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency.
  
  
  CONCLUSIONS
  There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.
authors.affiliation: Division of Infectious Diseases, University Hospital Berne, Berne, Switzerland. christoph.fux@insel.ch
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.forename: Mathew
authors.initials: M
authors.lastname: Simcock
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Milos
authors.initials: M
authors.lastname: Opravil
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D013557:Switzerland; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine