title: Neither boosted elvitegravir nor darunavir with emtricitabine/tenofovir disoproxil fumarate increase insulin resistance in healthy volunteers: results from the STRIBILD-IR study.
abstract: Insulin resistance (IR) was one of the first reported complications in HIV-positive patients who were receiving antiretroviral therapy (ART). However, the metabolic effects of newer fixed-dose ART combinations are unclear.
  
  
  
  This Phase I prospective randomized open-label study evaluated the effects on IR in 30 healthy volunteers who were receiving newer fixed-dose combinations of tenofovir disoproxil fumarate, emtricitabine, elvitegravir and cobicistat (E/C/F/TDF, 10 patients) or the established ART regimens, such as tenofovir disoproxil fumarate/emtricitabine with lopinavir/ritonavir (F/TDF+LPV/r, 9 patients) or darunavir/ritonavir (F/TDF+DRV/r, 9 patients). IR was measured before and after the 14-day treatments using the hyperinsulinemic-euglycemic clamp technique, and changes in IR were evaluated using the mean glucose disposal rate that was normalized to body weight (MBW) and lipid metabolism.
  
  
  
  The groups exhibited similar pretreatment IR, although MBWwas significantly lower after the 14-day F/TDF+LPV/r treatment compared with baseline (12.5 ±3.3 versus 9.2 ±1.8 mg glucose/min×kg; P=0.037). No significant IR changes were observed for E/C/F/TDF (11.2 ±3.2 versus 11.3 ±2.5) or F/TDF+DRV/r (11.6 ±2.5 versus 11.3 ±2.4). Compared with baseline, F/TDF+LPV/r and F/TDF+DRV/r treatments significantly increased day 14 triglyceride levels (62 [54-73] versus 119 [77-147] mg/dl, P=0.0109; 75 [56-95] versus 96 [93-128] mg/dl, P=0.009, respectively).
  
  
  
  Short-term treatment using fixed-dose combinations of E/C/F/TDF or F/TDF+DRV/r did not affect IR, although IR significantly increased after treatment using F/TDF+LPV/r.
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Spinner
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Kern
authors.affiliation: Department of Dermatology and Allergology, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zink
authors.affiliation: MUC RESEARCH, Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wolf
authors.affiliation: MUC RESEARCH, Munich, Germany.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Noe
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Von Werder
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schwerdtfeger
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Iakoubov
mesh_terms: D000328:Adult; D000069454:Darunavir / Q000494:pharmacology*; D000068679:Emtricitabine / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D007333:Insulin Resistance; D011446:Prospective Studies; D015363:Quinolones / Q000494:pharmacology*; D000068698:Tenofovir / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D015363:Quinolones; D014280:Triglycerides; C509700:elvitegravir; D000068698:Tenofovir; D000068679:Emtricitabine; D000069454:Darunavir