title: The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers.
abstract: BACKGROUND
  Certain antiretrovirals are known to affect lipid and glucose homeostasis. The aim of this study was to assess the effect on insulin sensitivity (determined by peripheral glucose uptake using a hyperinsulinaemic euglycaemic clamp) of tenofovir disoproxil fumarate (TDF) administration compared with placebo for 2 weeks in HIV-1-seronegative healthy male volunteers. Changes in lipids, adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and the adhesion molecules E-selectin and P-selectin were also assessed.
  
  
  METHODS
  This was a single-centre, randomized, double-blinded, placebo-controlled study that used a two-sequence, two-period cross-over design. A total of 19 HIV-negative males were recruited to the study and randomized 1:1 to receive either 2 weeks of TDF (300 mg once daily) followed by 2 weeks of placebo or placebo initially followed by tenofovir. Clamps were performed at baseline, after 2 weeks and after 4 weeks.
  
  
  RESULTS
  All three clamps were completed by 16 participants. During the euglycaemic clamp, there were no significant changes in insulin sensitivity after 2 weeks of TDF administration compared with placebo or baseline. There was a significant reduction in the mean total cholesterol (9.4%) and low-density lipoprotein (LDL; 8.1%) cholesterol following 2 weeks of TDF compared with placebo. Levels of adiponectin, leptin, PAI-1, P-selectin and E-selectin were not significantly altered.
  
  
  CONCLUSIONS
  TDF use for 2 weeks does not affect insulin sensitivity, as assessed by the hyperinsulinaemic euglycaemic clamp in HIV-negative male volunteers. TDF use resulted in modest, but statistically significant, reductions in total and LDL cholesterol.
authors.affiliation: Chelsea and Westminster Hospital, London, UK. paul.randell@chelwest.nhs.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Randell
authors.forename: Akil G
authors.initials: AG
authors.lastname: Jackson
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhong
authors.forename: Kitty
authors.initials: K
authors.lastname: Yale
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Moyle
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D054392:Adipokines / Q000378:metabolism*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D015309:Glucose Clamp Technique; D018023:HIV Seronegativity / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000068698:Tenofovir; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054392:Adipokines; D019380:Anti-HIV Agents; D008078:Cholesterol, LDL; D007328:Insulin; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D002784:Cholesterol; D000068698:Tenofovir; D000225:Adenine