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Abstract
Background: The phase 4, METABOLIK trial demonstrated that changes in metabolic parameters with darunavir with low-dose ritonavir (DRV/r) were comparable to those observed with atazanavir with low-dose ritonavir (ATV/r). A comprehensive assessment of the effects of these agents on insulin sensitivity will provide additional, relevant clinical information.
Methods: In this substudy of METABOLIK, HIV-1–infected, antiretroviral agent–naïve male subjects aged ≥18 years with a viral load of >1,000 copies/mL were randomized to receive DRV/r 800/100 mg once daily (qd) or ATV/r 300/100 mg qd, both with a fixed dose of tenofovir disoproxil fumarate/emtricitabine 300/200 mg qd. The effects of DRV/r versus ATV/r on insulin sensitivity over 48 weeks were compared using the euglycemic hyperinsulinemic clamp, the preferred method to assess insulin sensitivity; primary end point was the effect on insulin sensitivity during the first 12 weeks.
Results: Twenty-seven subjects completed the study. In the DRV/r arm (n = 14), median glucose disposal from baseline through weeks 12 and 48 was 9.3, 11.4, and 9.9 mg/kg*min, respectively; in the ATV/r arm (n = 13), these values were 8.9, 8.6, and 9.1 mg/kg*min, respectively. Median insulin sensitivity in the DRV/r arm at baseline, week 12, and week 48 was 24.0, 25.0, and 21.5 mg/kg*min per μIU/mL × 100, respectively; these values in the ATV/r arm were 20.7, 22.0, and 22.0 mg/kg*min per μIU/mL × 100, respectively. Most subjects had ≥1 adverse event, including three serious adverse events (n = 2 [DRV/r], n = 1 [ATV/r]).
Conclusions: DRV/r and ATV/r displayed similar modest effects on insulin sensitivity using a euglycemic hyperinsulinemic clamp.
Acknowledgements
The authors would like to thank the subjects and their families, the principal investigators (Carl Fichtenbaum, Nur Onen, Edgar T Overton, Frank Rhame, and Pablo Tebas), the METABOLIK substudy Janssen study team, and the study center staff for their participation in the substudy. Editorial support for this manuscript was provided by Courtney St. Amour, PhD, of MedErgy, and was funded by Janssen.