Famous weight loss drug may help people with HIV get healthier, MUSC researcher says

New findings from research that includes the work of infectious diseases specialist Allison Eckard, M.D., at the Medical University of South Carolina, show people with HIV appear to benefit from a well-known weight loss drug in ways that go beyond the numbers on a scale.

“It's a really good study and really very timely,” Eckard said. 

She and her colleagues are looking at ways to help people on antiretroviral treatment, or ART, fight some of the treatment’s side effects. People on ART tend to gain weight, some in potentially dangerous ways. 

The scientists recently gave an update of their findings at the Conference on Retroviruses and Opportunistic Infections in Denver. The study team includes researchers at University Hospitals Cleveland Medical Center, Case Western Reserve University and Ohio State University.

Findings

Doctors have long sought ways to help people with HIV live healthier lives. Eckard is happy to be part of that effort – an effort that has led to important new findings. 

 

She explained the core problem her team focused on. “There are some people with HIV who don’t just gain weight when they start ART but gain an excessive amount of visceral fat. Fat accumulates around their organs and in their abdominal cavities. And we know that’s the bad kind of fat,” she said.

“So our study targets people who have what we term HIV-associated lipohypertrophy, where most of the weight gain they experience with HIV treatment is from an abnormal accumulation of visceral fat.”

Unlike subcutaneous fat, the so-called pinchable kind, visceral fat is hidden deep in the body. “When you have the negative effects of both HIV and its treatment compounded on top of the already harmful effects of visceral fat, it creates even more dysfunctional fat and higher levels of inflammation in someone’s body. Too much inflammation, particularly when chronic, is bad for a person’s health,” Eckard said.

“It increases your risk of heart disease, and bone disease, and what we call sarcopenia, which in HIV is both a loss of muscle mass and muscle that doesn’t function as well. We also see a lot of metabolic comorbidities like insulin resistance and diabetes. These complications of the virus and its treatment occur commonly in people with HIV, but the risk is even higher in someone with HIV-associated lipohypertrophy.”

Comorbidities means having more than one health problem at a time, a common issue for people with HIV. “They have, on average, more comorbidities that occur at an earlier age than the general population. Many studies show that they occur about a decade sooner and in greater number,” Eckard said.

“Maybe somebody in the general population develops hypertension in their sixties. Well, somebody with HIV may develop diabetes, hypertension and even heart disease in their fifties. It’s one of the most pressing concerns and limitations of modern HIV treatment right now because we have very good antiretrovirals that allow people to live decades longer than before, but they often struggle with all these additional diagnoses that occur because of the indirect effects of HIV and its treatment.”

New potential use for weight loss drugs

Researchers in many fields are looking at the effects of the new weight loss drugs on a range of health conditions. Eckard’s study focuses on whether semaglutide (Ozempic, Wegovy) could not only help people with HIV lose weight – which could reduce the risk of a host of health conditions – but also reduce inflammation. 

“One of the key causes of comorbidities in HIV is chronic inflammation. Even if you have an undetectable viral load and are doing well, people with HIV have more inflammation and more immune dysfunction than somebody without HIV,” Eckard said.

“What we found in our study was that even in our adjusted models, C-reactive protein, a huge risk factor or predictor of cardiovascular disease, decreased by 40% in the group that received semaglutide versus the group that got placebo over 32 weeks. And what was really huge in our study, versus some of the studies in obesity or diabetes, is that the decrease in inflammation was independent of weight loss.”

Eckard said that’s probably related to the immune dysfunction that occurs in HIV. “We are still investigating why we saw such a dramatic reduction in levels of certain markers of inflammation, but perhaps semaglutide shifted some of the abnormal immune pathways to healthier ones. But the take-home message is that it decreased inflammation and is the most important finding from our data.”

Going forward

But further study is needed, she said. “We have to be cautious. Participants lost significant amounts of both visceral and subcutaneous fat and showed a decrease in lean body mass that likely includes some amount of muscle loss. So, I don't think this drug is for everybody. There are people still living with severe lipoatrophy from the very toxic drugs we used during the early part of the epidemic.” 

Lipoatrophy means an excessive unhealthy loss of subcutaneous fat. “You have to have some amount of subcutaneous fat to be healthy. So for people with severe lipoatrophy, a drug that causes additional subcutaneous fat loss would not be good for them. And, for some older, more frail individuals, we should be cautious about giving them a drug that could cause additional muscle loss. So those are the pieces we're still teasing out.”