Neither boosted elvitegravir nor darunavir with emtricitabine/tenofovir disoproxil fumarate increase insulin resistance in healthy volunteers: Results from the STRIBILD-IR study

Background: 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. Methods: 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 (M_BW) and lipid metabolism. Results: The groups exhibited similar pretreatment IR, although M_BW was 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/minxkg; 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). Conclusions: 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.