Background:  Some HIV-1 protease inhibitors (PI) are associated with insulin resistance. Healthy volunteer studies of unboosted 400 mg atazanavir (ATV) for 5 days did not alter glucose disposal rates during hyperinsulinaemic euglycaemic clamp. Changes observed in similar studies have included a 10% reduction in glucose disposal with atazanavir/ritonavir (ATV/r) 300/100 mg, a 17% reduction in glucose disposal on indinavir (IDV) for 4 weeks, and a 23% lower insulin sensitivity index with lopinavir/ritonavir (LPV/r) over 5 days of therapy. There are no data on the effect of either atazanavir or saquinavir (SQV) on glucose disposal when given as part of initial regimens to HIV-1-infected patients.

Methods:  A single-center, prospective randomized, open-label trial comparing the SQV/r 2000/100 mg with ARV/r 300/100 mg, with tenofovir (TDF)/emtricitabine (FTC) on glucose disposal rates during hyperinsulinemic euglycemic clamp performed at baseline and after morning dosing at week 4.

Results:  We randomized 22 HIV-1-infected males, naοve to ART and without metabolic disorders. Whole-body insulin sensitivity was determined by 180 minute hyperinsulinemic euglycemic clamp (40 mUnit.m^–2.min^–1). We assigned 10 patients to the SQV arm and 12 to ATV with mean age (SD) of 38 (±5.1) vs 38 (±4.6) years. Baseline median CD4 count was 224 vs 232 cells.mm^–3, with a median viral of 5.00 vs 4.92 log₁₀ copies.mL^–1 for SQV and ATV arms, respectively. Mean (SD) total body mass were 70.8 kg.m^{–2  (}11.7 and 23.1) for SQV compared with 75.5 kg.m^–2  (8.2 and 25.5) for ATV. The median percentage change in glucose disposal rate for treatment with SQV was a 10.8% decrease (range –33.6 to +32.0%) compared with a median increase of 2.3% (range –26.4 to +103.7%) in those patients on ATV. Median changes in lipid parameters over 4 weeks for SQV and ATV were:  total cholesterol (+7.4 vs +6.1%), fasting triglycerides (+39.4 vs +11.5%), HDL cholesterol (+0.7 vs +7.9%), and LDL-cholesterol (+0.7 vs +4.0%), respectively.

Conclusions:  Variable changes in glucose disposal are seen with both SQV/r and ATV/r at 4 weeks after initiation of antiretroviral therapy, with a modest median reduction in glucose disposal with SQV/r. Changes observed in the HIV treatment setting may differ from those observed in healthy volunteers. Lipid changes were modest with more favorable changes in triglycerides and HDL observed with ATV/r.