DENVER — People with HIV who received semaglutide (Ozempic, Wegovy) had reduced levels of several inflammatory biomarkers associated with cardiovascular disease, a randomized controlled trial showed.

After 32 weeks, interleukin (IL)-6 levels decreased by 18.8%, high-sensitivity C-reactive protein (hsCRP) levels decreased by 39.9%, and soluble CD163 levels decreased by 12.3% with the GLP-1 receptor agonist, while the placebo group had nonsignificant changes in these biomarkers, reported Allison Ross Eckard, MD, of the Medical University of South Carolina in Charleston, during the Conference on Retroviruses and Opportunistic Infections.

“Weight gain associated with antiretroviral therapy [ART] is a major problem with HIV,” Eckard noted, but “more concerning is the increased accumulation of visceral adipose fat and ectopic fat depots in people with HIV associated with lipohypertrophy.”

Lipohypertrophy contributes to chronic inflammation and cardiometabolic risk in people with HIV, but there are currently few treatments, and they often have ineffective response rates.

Past research has shown that semaglutide significantly reduced central adipose tissue, particularly visceral adiposity, in people with HIV who have lipohypertrophy. Research has also shown that GLP-1 receptor agonists decrease systemic inflammation, though the mechanisms by which they do that are unclear. These new findings, Eckard said, suggest “perhaps that semaglutide would be an effective treatment for lipohypertrophy.”

As previously reported at IDWeek 2023, patients taking semaglutide experienced a 30.6% reduction in visceral adipose tissue, an 11.2% reduction in subcutaneous adipose tissue, a 10.4% loss of body weight, and a 5.7% loss in lean body mass at 32 weeks.

Frank Palella, MD, of Northwestern University Feinberg School of Medicine in Chicago, told MedPage Today that “it’s not terribly surprising that overall loss of weight would also result in beneficial reductions in systemic inflammation.”

“It is curious, though, that the fat reduction was not directly correlatable with the inflammation reduction, since we’re used to fat being a source of inflammation,” he added. “What remains to be seen are the long-term benefits of the weight loss, the fat loss, and the inflammation reduction all together.”

Todd Brown, MD, PhD, of Johns Hopkins University in Baltimore, who moderated the session, said it will be important to find out whether GLP-1 physiology is any different in people with HIV compared with those without it.

In the REPRIEVE trial, for example, people with HIV saw a greater cardiovascular benefit from the low-density lipoprotein cholesterol-lowering effects of pitavastatin (Livalo) than people without HIV usually see from statins. Considering that and what we still don’t know about GLP-1 agonists’ effects in people with HIV, “the physiology may be different, and so the management strategy may be different,” he told MedPage Today.

Brown said these results were impressive and expects the next phase, looking at cellular effects from GLP-1 agonists in people with HIV, to “be even more impressive.”

“One of the proposed drivers of a lot of the comorbid diseases that we see in people with HIV is increased systemic inflammation,” he noted. With systemic inflammation linked to cardiovascular disease, diabetes, osteoporosis, kidney disease, impaired cognition, and various other conditions, a major goal in the HIV field has been to target inflammation to decrease the burden of these comorbidities, but few interventions have had success.

The cardiovascular benefits of GLP-1 agonists may be due to the glucose and fat reduction effects and direct effects on the vascular endothelium and the myocardium, he said, “but some of it may be mediated through decreasing inflammation, so if there were a big cardiovascular outcome trial in people with HIV with GLP-1 receptor agonists, would we see an even better benefit than we’ve seen in the SELECT trial?”

The study included 108 adults with HIV who did not have diabetes, but had a body mass index (BMI) of 25 or greater, a waist circumference/waist-to-hip ratio of at least 95 cm for men and 94 cm for women, and subjective increased abdominal girth after beginning ART.

All participants were virologically suppressed and had been stable on ART for at least 12 weeks. Patients with diabetes, cardiovascular disease, severe lipoatrophy, or pregnancy were excluded. Most participants were Black (61%) men (70%) on integrase inhibitors (83%), with an average age of 52.

In the intervention arm, 54 participants received 24 weeks of 1-mg subcutaneous semaglutide injections after an 8-week titration phase. The other 54 participants received placebo.

In this analysis, the researchers used beta coefficients in linear regression to estimate the inflammation-related effects between the semaglutide and placebo groups at 32 weeks, adjusted for baseline marker values, smoking, male sex, and age. Only hsCRP was significant (β -0.51, 95% -0.87 to -0.15, P=0.006), while the difference for IL-6 was -0.21 (95% CI -0.44 to 0.02, P=0.074) and -0.13 for soluble CD163 (95% -0.26 to -0.002, P=0.046).

The anti-inflammatory effects of semaglutide were not explained by decreases in weight, Eckard reported, with no significant correlation between hsCRP change and weight or between hsCRP change and changes in visceral adipose tissue.

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