Among the challenges of living with HIV is a higher risk of fatty liver, a condition that can lead to chronic disease, a liver transplant or even death. Kristine Erlandson, MD, a University of Colorado Department of Medicine faculty member, has found that a medication used to treat diabetes and obesity – and touted on social media for weight loss – can be a powerful weapon against a type of fatty liver disease in people with HIV. Erlandson is an associate professor in the Division of Infectious Diseases. Her research is focused on helping people with the human immunodeficiency virus, or HIV, live longer lives despite the health challenges they often face.
In their study, published April 30 in the journal Annals of Internal Medicine, Erlandson and colleagues across the United States and in Brazil focused on the use of a medication called semaglutide in treating metabolic dysfunction-associated steatotic liver disease, or MASLD, among people living with HIV.
MASLD is the most common cause of chronic liver disease and of liver-related deaths. It’s a new term for what used to be called nonalcoholic fatty liver disease, which as the name suggests is not linked to drinking alcohol. It’s associated with at least one metabolic risk factor, such as obesity or high cholesterol.
“It basically just means increased fat in the liver,” Erlandson says. “Fatty liver is one of the more common reasons for a liver transplant in the U.S. We know that fatty liver occurs in about 25% to 30% of the general population, but it occurs in up to 50% of people with HIV.”
In some cases, fatty liver in people with HIV can be related to the side effects of certain antiretroviral therapies, particularly older ones, she says. It appears that HIV may help to accelerate MASLD’s progression to liver damage, cirrhosis, and liver failure.
Best known as Ozempic, Wegovy
“Currently the mainstay of treatment for fatty liver is weight loss, and we all know that weight loss can be difficult for many people to achieve and to ultimately maintain,” Erlandson says. That led her and her colleagues to focus on investigating semaglutide as a therapy.
Semaglutide was approved by the U.S. Food & Drug Administration in 2017 as a treatment for type 2 diabetes, often under the brand name Ozempic. More recently, a higher dosage of semaglutide, sold as Wegovy, was approved for use for treating obesity or for managing weight with accompanying health conditions.
Lately, the drug has gained widespread popularity as an off-label treatment for general weight loss, boosted by internet chatter and celebrity endorsements.
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“Because weight loss is the recommendation for fatty liver, and there aren’t any approved therapies for decreasing liver fat, our idea was that if we had an effective drug for weight loss, we would likely see improvements in fatty liver,” Erlandson says.
Fatty liver also is associated with metabolic dysfunction involving regulation of glucose, she adds. “If we could target that metabolic aspect, too, we might have greater improvement. There also appear to be anti-inflammatory and immune changes associated with this class of drugs. Since this may contribute to progression of fatty liver in people with HIV, we thought that the immune and inflammation pathways may be a unique aspect of how this drug may work in people with HIV and fatty liver, making it more effective than just giving a different weight-loss drug.”
A highly effective therapy
For the trial, adult participants with HIV and MASLD were recruited in the United States and Brazil. Participants also had a larger-than-typical waist circumference, but they were not necessarily overweight. It was an “open label, single arm” study, meaning that there was no control group getting a placebo, and participants knew what drug they were getting.
After 24 weeks, the participants were evaluated; 29% showed no signs of MASLD, and another 58% showed significant reductions in liver fat, enough to lower their risk of progression to advanced liver disease. “And we saw improvements in many other metabolic markers,” Erlandson says. “Not surprisingly, we saw very impressive weight loss among essentially all of our participants.”
The study concluded that semaglutide is “a highly effective MASLD therapy” for people with HIV. It also found evidence that the drug may reduce risk of cardiovascular disease, which is higher among people with HIV, by reducing liver fat.
→ Current HIV-related clinical trials and other research studies on the CU Anschutz Medical Campus.
Erlandson notes that study participants were given a smaller dose of semaglutide than the FDA now allows. “I suspect if we’re using the larger doses now approved, we’ll see an even greater benefit,” she says.
Meanwhile, she hopes that insurance companies can be convinced to treat fatty liver as a qualifying condition for semaglutide, “because many patients can’t afford to pay for it out of their pocket and insurance often won’t cover it.”
Aging differently with HIV
Erlandson says she got interested in her research specialty during her infectious disease fellowship. “A lot of the patients we were seeing in the hospital who had HIV weren’t hospitalized with advanced HIV, but instead for things like heart attacks or fatty liver complications or hip fractures, things that really seemed related to age, but at much younger ages than I’d expect,” she says. “There were signs of accelerated or accentuated aging with HIV. At the time, this was a new topic.”
When it was first identified in 1983, with no effective treatments, HIV amounted to a death sentence, leading inevitably to AIDS. Over time, new and better treatments have been developed, extending life expectancy. As a result, researchers like Erlandson are investigating how people with HIV “may age differently than the general population. I’ve been really interested in how we can help people age with HIV successfully to the same age as their peers without HIV.”
She adds: “A lot of my patients in my clinic are older men who had many friends or partners who died from AIDS early on, and they have gone on to live with it for almost 40 years now. I listen to them say, ‘Initially, my doctor said, go have fun, because there’s no reason not to, you’re not going to live, essentially.’ And then one day, that changed to, ‘Oh, I am living. I should start eating better and exercising. Now I need to focus on how I can live another 40 years.’ It was an abrupt shift in how we think about care.”
Photo at top: Kristine Erlandson, MD, presents at the 2024 Conference on Retroviruses and Opportunistic Infections in Denver. Photo courtesy of Kristine Erlandson.
