The AIDS Clinical Trials Group (ACTG) has announced promising cardiovascular findings from the SLIM LIVER study, demonstrating that semaglutide significantly improved multiple biomarkers of cardiovascular risk in people living with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD). The results were presented at the 2025 AASLD Liver Meeting in Washington D.C.
First-of-Its-Kind Trial in HIV Population
SLIM LIVER (ACTG A5371) represents the first clinical trial to test semaglutide as a treatment for MASLD specifically in people living with HIV. MASLD, previously known as non-alcoholic fatty liver disease (NAFLD), is a condition where fat accumulates in the liver and poses particular risks for HIV patients, who may experience faster liver damage and increased organ dysfunction compared to the general population with MASLD.
"This SLIM LIVER analysis provides important insights into the impact of semaglutide on a whole host of cardiovascular biomarkers for people living with HIV and MASLD," said ACTG Chair Joseph J. Eron, M.D., from the University of North Carolina. "People living with HIV are at increased risk for cardiovascular disease and they experience MASLD in greater numbers than the general population."
Study Design and Patient Population
The current cardiovascular analysis included 36 people living with HIV who were taking antiretroviral therapy (ART) and had MRI-defined MASLD. The study population had a median age of 52 years and median BMI of 34 kg/m². The demographic breakdown showed 39 percent were Hispanic, 28 percent were Black, and 45 percent were female. Additionally, 77 percent of participants were taking an ART regimen containing an integrase inhibitor.
Independent Cardiovascular Benefits
The analysis revealed significant reductions in cardiovascular risk-associated lipoproteins and glycoproteins that were notably independent of the changes in weight, liver fat, or insulin resistance previously reported in the primary analysis. This finding suggests that semaglutide operates through an independent mechanism to provide cardiovascular protection beyond its established metabolic effects.
"While larger studies with clinical endpoints are still needed to optimize cardiovascular risk among people living with HIV and MASLD, these findings are an important first step in understanding the impact of semaglutide among these individuals and have the potential to meaningfully impact their health," said lead author Jordan E. Lake, M.D., M.Sc., from UTHealth Houston.
Building on Previous MASLD Findings
Today's cardiovascular data expands upon previously presented primary results from SLIM LIVER, which showed that semaglutide improved weight, intra-hepatic triglyceride content, insulin resistance, glucose, and triglycerides in HIV patients with MASLD. The primary analysis had demonstrated that semaglutide not only improved MASLD but in some cases resolved the condition completely among people living with HIV.
Clinical Significance for HIV Care
The findings address a critical unmet need in HIV care, as MASLD is increasingly recognized as a major contributor to illness and death among people living with HIV. Lake emphasized that "identifying treatments that can attenuate its impact is an important priority in HIV research."
ACTG Chair Eron noted the organization's commitment to addressing HIV comorbidities: "ACTG is committed to conducting research that identifies solutions to the comorbidities that most impact people living with HIV and we are encouraged by these results."
Research Leadership and Funding
SLIM LIVER is led by Dr. Lake and Kristine Erlandson, M.D., from the University of Colorado Anschutz as Co-Chairs, with Fred Sattler, M.D., from the University of Southern California serving as Vice Chair. The study is sponsored by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) and received additional funding from UTHealth Houston McGovern School of Medicine.
