New findings from research including that of infectious disease specialist Allison Eckardt, M.D., of the Medical University of South Carolina, suggest that people with HIV may benefit from a popular weight-loss drug in ways that go beyond the number on the scale.
“This is a really fascinating study and very timely,” Eckerd said.
She and her colleagues are looking for ways to help people on antiretroviral therapy (ART) combat the side effects of their treatment, which can be dangerous as it makes them prone to weight gain.
The scientists, who presented an update on their findings recently at the Conference on Retroviruses and Opportunistic Infections in Denver, included researchers from University Hospitals of Cleveland, Case Western Reserve University and Ohio State University.
Investigation result
Doctors have long been searching for ways to help people with HIV live healthier lives, and Eckardt is pleased to be part of that effort, which has led to an important new discovery.
She explained the core problem the team focused on: “Some people with HIV not only gain weight when they start ART, but they also accumulate excess visceral fat – fat that accumulates around the organs and in the abdominal cavity. And we know that it's the bad kind of fat,” she said.
“Our study therefore focuses on patients with what's called HIV-associated lipohypertrophy. Most of the weight gain experienced with HIV treatment is due to the abnormal accumulation of visceral fat.”
Unlike subcutaneous fat, or the fat you can pinch, visceral fat is hidden deep within the body. “When the already harmful effects of visceral fat are compounded with the negative effects of HIV and its treatment, you end up with even more dysfunctional fat and inflammation levels in the body. Too much inflammation, especially chronic inflammation, has negative effects on health,” says Eckerdt.
“There's an increased risk of heart disease, bone disease, and a condition called sarcopenia, which involves both loss of muscle mass and muscle function in people with HIV. There are also more metabolic complications, such as insulin resistance and diabetes. These complications from the virus and its treatments are common in people with HIV, but those with HIV-associated lipohypertrophy are at even higher risk.”
Comorbidity means having more than one health problem at once, and it's a common problem among people with HIV. “People with HIV, on average, tend to develop comorbidities at a younger age than the general population. Many studies have shown that comorbidities develop as much as 10 years earlier and are increasing in number,” Eckerd said.
“Someone in the general population may develop hypertension in their 60s, whereas someone with HIV may develop diabetes, hypertension or even heart disease in their 50s. This is currently one of the most pressing concerns and limitations of modern HIV treatment, because we have very good antiretroviral drugs that allow us to live decades longer than before. But many people suffer from all these additional diagnoses that arise as an indirect effect of HIV and its treatment.”
New possibilities for weight loss drugs
Researchers in many fields are studying the effects of newer weight-loss drugs on a variety of health conditions. Eckardt's research focuses on whether semaglutide (Ozempic, Wegovy) can help people with HIV lose weight (potentially reducing the risk of a variety of health conditions) but also reduce inflammation.
“One of the main causes of HIV complications is chronic inflammation,” Eckerd says. “Even when people with HIV have undetectable viral loads and are in good health, they are more likely to develop inflammation and immune dysfunction than people without HIV.”
“What we found in our study is that even in adjusted models, C-reactive protein, which is a big risk factor or predictor of cardiovascular disease, was reduced by 40% over 32 weeks in the group receiving semaglutide compared with the group receiving placebo. And what's really big in our study, compared with some studies on obesity and diabetes, is that the reduction in inflammation was independent of weight loss.”
Eckardt said this was probably related to the immune dysfunction that occurs with HIV: “We're still investigating why levels of certain markers of inflammation dropped so dramatically, but perhaps semaglutide redirected some of the abnormal immune pathways into healthier ones. But the key is that inflammation was reduced, and this is the most important finding from our data.”
from now on
But more research is needed, she says: “We have to be cautious. Participants lost a significant amount of both visceral and subcutaneous fat, and showed a loss of lean body mass, which appears to include muscle loss. So I don't think this drug is suitable for everyone. There are people out there who are still suffering from severe lipoatrophy due to the very toxic drugs used early in the epidemic.”
Lipoatrophy means an unhealthy excess loss of subcutaneous fat. “You need some subcutaneous fat to be healthy, so if someone has severe lipoatrophy, drugs that will further reduce that fat are not appropriate. And if someone is older and frail, you have to be careful about giving them drugs that might further reduce muscle. So these are some of the things we're still figuring out.”
