Impact of semaglutide on liver fibrosis score in people with HIV: findings from the CNICS cohort

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis are key drivers of morbidity and mortality in people with HIV (PWH). Limited evidence exists in PWH for managing MASLD and liver fibrosis with semaglutide. METHODS: We studied adult PWH in care at 10 CFAR Network of Integrated Clinical Systems sites who initiated semaglutide for diabetes and/or weight loss and had liver fibrosis score (FIB-4) data from 4/2018-11/2024. We used adjusted linear mixed models for a quasi-experimental, pre-/post-, new-user analysis of semaglutide on FIB-4 score with several a priori stratifications by baseline fibrosis category and other relevant clinical factors. RESULTS: Among 1850 PWH at baseline, 1368 had FIB-4 2.67 (advanced fibrosis). Most PWH had cardiometabolic conditions (diabetes 59%, dyslipidemia 62%, hypertension 80%, BMI ≥30 80%), drank alcohol with low levels of use (57%, mean AUDIT-C 1.6), and did not have hepatitis B (93%) or hepatitis C infection (86%). Mean time on semaglutide was 218 days. Semaglutide was associated with reductions in liver fibrosis score in PWH with baseline moderate-to-advanced fibrosis (FIB-4 ≥1.3; ΔFIB-4: -0.11, P < 0.01) with greatest decreases in advanced fibrosis (FIB-4 >2.67; ΔFIB-4: -0.64, P < 0.001). CONCLUSIONS: Semaglutide was associated with declines in liver fibrosis scores in PWH with moderate-to-advanced fibrosis and high levels of cardiometabolic conditions. Together with evidence from the general population, these findings suggest that semaglutide could help manage MASLD and liver fibrosis in PWH, especially as PWH age and experience long-term impacts of cardiometabolic disease.