According to a recent presentation at the Conference on Retroviruses and Opportunistic Infections (CROI), a weekly injection of semaglutide has shown promising results in reducing liver fat in individuals with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD). This marks the first clinical trial of semaglutide for MASLD in people living with HIV.

The study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), was conducted in the United States and Brazil by ACTG, a global clinical trials network focused on HIV and other infectious diseases. Funding for the research was also contributed by the McGovern Medical School at UTHealth Houston.

MASLD, previously known as nonalcoholic fatty liver disease, is a condition characterized by the buildup of excess fat in the liver, unrelated to alcohol consumption or viral hepatitis. Over time, this can lead to inflammation, cellular damage, and increase the risk of cardiovascular and liver diseases. MASLD is commonly associated with obesity, type 2 diabetes, and other metabolic disorders. It is a leading cause of chronic liver disease in the United States and a significant factor for liver transplantation.

In the Phase 2b pilot study, 49 participants with HIV and MASLD, aged 18 and older, were enrolled. All participants had their viral load effectively suppressed to undetectable levels through antiretroviral therapy (ART). The participants represented diverse ethnicities, races, genders, and age groups. The majority (82%) of participants were on ART regimens that included an integrase strand transfer inhibitor, a class of antiretroviral drugs known for effectively suppressing HIV but sometimes associated with weight gain.

Throughout the study, participants self-administered semaglutide injections on a weekly basis, gradually increasing the dosage until reaching 1 milligram at week four. The study team closely monitored the participants' safety during frequent visits. After 24 weeks, the researchers assessed the changes in liver fat content using a specialized MRI designed to measure liver fat. On average, participants experienced a remarkable 31% reduction in liver fat, with 29% achieving complete resolution of MASLD, where liver fat decreased to 5% or less of the overall liver content.

Notably, participants also observed weight loss and improvements in fasting blood glucose and fasting triglyceride levels, consistent with previous studies on semaglutide in individuals without HIV. A separate analysis further indicated a decrease in the volume of the psoas muscle, a large muscle connecting the torso to the lower body, without significant changes in physical function.

Semaglutide, already approved as an antidiabetic medication for type 2 diabetes and for long-term weight management, exhibited a favorable safety profile throughout the study. Gastrointestinal adverse events such as nausea, diarrhea, vomiting, and abdominal pain were the most frequently reported side effects. Only two participants experienced more significant adverse events potentially linked to semaglutide but were able to continue in the study. Importantly, all participants completed the full 24 weeks of therapy as prescribed.

These findings suggest that semaglutide is a safe and effective therapy for individuals with HIV and MASLD. The study's results provide valuable insights that can inform healthcare decisions by individuals and their healthcare providers, supporting a holistic approach to healthier aging with HIV over the lifespan. The researchers are currently conducting further investigations to explore any unique immunologic or inflammatory pathway changes in people with HIV undergoing semaglutide therapy.

The research conducted by NIAID, ACTG, and their collaborators sheds light on potential treatment options for MASLD in the context of HIV. By investigating the causes, prevention, diagnosis, and treatment of infectious and immune-mediated diseases, NIAID continues to contribute towards better health outcomes. These findings represent another step forward in turning scientific discoveries into improved healthcare for individuals living with HIV and metabolic dysfunction-associated steatotic liver disease.

For further inquiries and discussions regarding this research, Dr. Sarah Read, deputy director of NIAID's Division of AIDS, is available. Additional information about NIAID and its research can be found on the official NIAID website. The National Institutes of Health (NIH), the primary federal agency dedicated to medical research, supports and conducts a wide range of studies to advance medical knowledge and find solutions for both common and rare diseases.