ACTG Presents Four Studies at CROI Describing Findings from SLIM LIVER

Presentations highlight relationship between semaglutide and blood markers of gene modification age predictors, gut bacteria, heart and metabolic effects, and fat in the liver

LOS ANGELES, March 10, 2025 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced new findings from the SLIM LIVER study (also known as A5371). These data suggest that blood-based epigenetic biomarkers (gene modifications) may help predict how well people living with HIV respond to semaglutide as a treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). These results were presented in the oral abstract, “Epigenetic Age Predictors of Semaglutide-Related Liver Fat Changes in People With HIV,” at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, California.

SLIM LIVER was the first clinical trial to test semaglutide as a treatment for MASLD in people living with HIV. MASLD, previously known as non-alcoholic fatty liver disease (NAFLD), is a common and serious condition in which fat builds up in the liver. In people living with HIV, MASLD may cause faster liver damage than in people with MASLD but without HIV and increase the risk of organ dysfunction. While semaglutide (a medication commonly used for weight loss and diabetes) has been associated with cardiometabolic improvements in the general population, the primary analysis of SLIM LIVER was the first time that it was shown to improve, and in some cases resolve completely, MASLD among people living with HIV.

New Findings: Can Blood Markers Predict Who Benefits Most?
The secondary SLIM LIVER analysis that was presented today used clinical samples from the study to measure epigenetic biomarkers in blood cells. These biomarkers are based on DNA methylation—chemical changes in DNA that reflect aging and lifestyle factors. By analyzing these changes, researchers can estimate biological age, as well as risks for diseases, mortality, and overall physical fitness. In this analysis, the team investigated whether these epigenetic biomarkers could help predict how well a person living with HIV and MASLD would respond to semaglutide treatment.

At the beginning of the study, the average age of SLIM LIVER participants was 49 years old, but their average epigenetic (biological) age was 59.2 years—showing that their bodies were aging faster than expected. One of the key biomarkers examined in this study was DNAmGripmax, an epigenetic measure correlated with grip strength that provides insight into a person’s muscle function and biological aging. Researchers found that participants whose measure of epigenetic age that includes this grip strength marker was lower (meaning their muscle function appeared weaker at a biological level) experienced greater reductions in liver fat after taking semaglutide. This suggests that individuals whose bodies are aging faster in terms of muscle function may benefit more from this treatment.

“Today’s data from SLIM LIVER highlight the potential of epigenetic age biomarkers to identify individuals who will benefit most from semaglutide treatment, marking an important step toward translating these insights into meaningful, actionable strategies in clinical care for people living with HIV,” said Michael Corley, Ph.D., University of California San Diego, who led this secondary analysis.

Additional SLIM LIVER Findings at CROI
ACTG researchers also presented three posters with further insights from the SLIM LIVER study:

• How Semaglutide Affects Gut Bacteria in People with HIV (Stephanie Dillon, et al.)
• Semaglutide’s Impact on Heart Health and Metabolism (Jordan Lake, et al.)
• How Semaglutide Reduces Liver Inflammation in People with HIV (Jordan Lake, et al.)
  

“The primary findings from SLIM LIVER were groundbreaking for people living with HIV, and we are eager to add to that body of knowledge with our four presentations at CROI,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “We are particularly excited about the findings that minimally invasive biomarkers have the potential to help us better identify which people living with HIV will benefit most from treatment with semaglutide.”

SLIM LIVER is led by Jordan E. Lake, M.D., M.Sc., UTHealth Houston and Kristine Erlandson, M.D., University of Colorado Anshchutz (Co-Chairs), and Fred Sattler, M.D., University of Southern California (Vice Chair). ACTG is led by Dr. Eron and Rajesh T. Gandhi, M.D., Massachusetts General Hospital and Harvard Medical School (ACTG Vice Chair). It is sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634, and received additional funding from UTHealth Houston McGovern School of Medicine.

About ACTG
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.

Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH.

Media Contact:
Rachel Reiss, ACTG
RLReiss@mednet.ucla.edu