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

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 MBW 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/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.