Background:
Metabolic-Associated Steatotic Liver Disease (MASLD) is common among people with HIV (PWH) and likely synergistic with HIV-1 to accelerate hepatic injury and organ dysfunction. The glucagon-like peptide-1 receptor agonist semaglutide is associated with cardiometabolic improvements in the general population through its effects on weight reduction and systemic inflammation. We designed a phase IIb, single-arm, pilot study of the effects of semaglutide on magnetic resonance imaging-proton density fat fraction (MRI-PDFF)-quantified intrahepatic triglyceride (IHTG) content in PWH and MASLD.
Methods:
ACTG A5371 enrolled PWH ≥18 years of age on suppressive antiretroviral therapy (ART) with central adiposity, insulin resistance or pre-diabetes and SLD (defined as ≥5% IHTG on MRI-PDFF). All participants received semaglutide for 24 weeks (titrated to 1mg sc weekly by week 4). IHTG content was measured by a central, blinded reader. Mean changes and 95% confidence intervals (CI) were estimated using linear regression. Spearman correlations assessed associations between outcome measures.
Results:
Participants (n=49) had median age 52 years, BMI 35 kg/m2, 39% Hispanic ethnicity and 33% Black/African American race; 43% were cis or trans women and 82% were on integrase strand transfer inhibitor-based ART. Semaglutide was well-tolerated, with only 2 possibly-related Grade 3 (1 nausea, 1 serotonin syndrome) and no Grade 4 adverse events. Mean baseline (standard deviation) IHTG was 12.7% (6.1%). Mean (95% CI) absolute and relative declines in IHTG were -4.2% (-5.4, -3.1) and -31.3% (-39.0, -23.6), respectively (both p<0.001); 29% of participants had complete resolution of MASLD (absolute IHTG <5%); and 58% had a ≥30% relative reduction in IHTG. Trends toward greater improvements in IHTG were seen in women, Hispanics, non-Hispanic whites and with increasing age. Significant improvements in weight, waist circumference, fasting glucose and triglyceride concentrations were also observed (Table). Improvements in IHTG correlated with weight loss on semaglutide (r=0.54, p<0.0001).
Conclusions:
Low-dose (1mg weekly) semaglutide is a safe and effective pharmacologic therapy for MASLD in PWH and shows evidence of broader cardiometabolic benefit. Further analyses will assess specific immunologic and inflammatory pathway changes with semaglutide therapy in PWH, including those that may be unique to this population.
