title: Renal function in antiretroviral-experienced patients treated with tenofovir disoproxil fumarate associated with atazanavir/ritonavir.
abstract: OBJECTIVE
  To determine the evolution of renal function in highly treatment-experienced patients with normal renal function at baseline receiving tenofovir disoproxil fumarate (TDF) as part of a fixed combined antiretroviral regimen and to identify prognostic factors of change in renal function, including tenofovir concentrations.
  
  
  METHODS
  A prospective 48-week open-label trial was carried out, evaluating the safety of TDF, associated with atazanavir/ritonavir, and optimized nucleoside reverse transcriptase inhibitors, in patients with documented failure in previous treatments. Statistical analysis was performed on an intent-to-treat basis.
  
  
  RESULTS
  Fifty-three patients were included, with a median CD4+ T-cell count of 206 x 10(6)/l and a median HIV RNA level of 5 log10 copies/ml. All patients had normal serum creatinine levels and creatinine clearances (CL(Cr)) at baseline, which were stable within the 2 months preceding inclusion. Two patients discontinued TDF as a result of severe renal impairment. Two patients never started TDF. A total of 49 patients without clinical nephrotoxicity were analysed. The median creatinine level increased significantly from baseline to week 48 (+0.04 mg/dl [+5.8%]; P = 0.008), and the median CL(Cr) decreased significantly (-7.8 ml/min [-7.6%]; P = 0.005). Trough tenofovir concentration was not associated with change in CL(Cr), (P = 0.79). No risk factors, including tenofovir plasma trough levels, were significantly associated with change in CL(Cr) at week 24.
  
  
  CONCLUSIONS
  This study confirms that TDF-related severe nephrotoxicity is an uncommon event. In patients without clinical nephrotoxicity, the use of TDF during a 1-year period was associated with a slight but significant alteration of renal function, which was not associated with increased trough concentration.
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.forename: Corine
authors.initials: C
authors.lastname: Chazallon
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.forename: Christophe
authors.initials: C
authors.lastname: Piketty
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009842:Oligopeptides / Q000627:therapeutic use*; D063065:Organophosphonates / Q000009:adverse effects* / Q000493:pharmacokinetics; D011379:Prognosis; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine; D019438:Ritonavir