Novel MRI assessment of treatment response in HIV-associated NAFLD: a randomized trial of an SCD1 inhibitor (ARRIVE Trial)

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 (SCD1) inhibitor, has been shown to reduce hepatic-fat content in patients with primary nonalcoholic-fatty-liver-disease (NAFLD), however, its effect in patients with HIV-associated NAFLD is unknown. The ARRIVE trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by MRI-proton-density-fat-fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n=25) or placebo (n=25) for 12 weeks. The primary endpoint was a change in hepatic-fat as measured by MRI-PDFF in co-localized regions-of-interest. Secondary endpoints included changes in liver-stiffness using MR-elastography (MRE) and vibration-controlled-transient-elastography (VCTE) and exploratory endpoints included changes in total body fat and muscle depots on DXA, whole-body and cardiac MRI. The mean (±SD) of age and BMI were 48.2±10.3 years and 30.7±4.6kg/m2 respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline-MRI-PDFF:15.6% vs end-of-treatment MRI-PDFF:14.4%, p=0.24) versus placebo at -1.4% (baseline-MRI-PDFF:13.3% vs end-of-treatment MRI-PDFF:11.9%, p=0.26), respectively. There was no difference in the relative decline in mean MRI-PDFF between aramchol group and placebo (6.8% versus 1.1%, p=0.68). There were no differences in MRE and VCTE derived liver-stiffness, and whole body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events.

CONCLUSION: Aramchol, over a 12-week period, did not reduce hepatic-fat or change body fat and muscle composition by utilizing novel MRI-based assessment in patients with HIV-associated NAFLD.