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  Conference on Retroviruses
and Opportunistic Infections
Denver, Colorado
March 3-6 2024
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Semaglutide Lowers Some Inflammation Markers in HIV Lipohypertrophy
  CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver
Mark Mascolini
In people with HIV-linked lipohypertrophy but not diabetes, 32 weeks of the weight-loss drug semaglutide significantly lowered levels of two inflammation/activation markers-high-sensitivity C-reactive protein (hsCRP) and sCD163-while trimming levels of a third marker, IL-6, nonsignificantly [1]. The results came in a trial that measured significant drops in total body fat and central fat, especially visceral adipose tissue (VAT), in these 108 people with lipohypertrophy [2].
Allison Eckard (Medical University of South Carolina) and collaborators at other centers noted that HIV-associated lipohypertrophy contributes to systemic inflammation and heightens cardiovascular risk. Evidence that semaglutide not only lowers central fat but also deflates levels of biomarkers tied to cardiovascular disease would add to the rationale for prescribing semaglutide if research further validates its merits and safety in people with HIV lipohypertrophy.
This single-center, double-blind phase 2b trial randomized enrollees in a 1-to-1 ratio to semaglutide, titrated up to 1 mg weekly by week 8 and given at that dose through week 32. Participants had to be at least 18 years old with a viral load below 400 copies for at least 6 months on stable antiretroviral therapy (ART). Physical requirements were a body mass index of at least 25 kg/m2, waist circumference above 95 cm in men and 94 cm in women, a waist-to-hip ratio above 0.94 in men and 0.88 in women, and the subjective impression that they added abdominal girth after starting ART. The trial excluded anyone with diabetes, known cardiovascular disease, and a few other serious conditions.
Researchers randomized 54 participants to semaglutide and 54 to placebo. Median ages in the semaglutide and placebo groups were 53 and 53. Respective proportions of men were 70% and 50%, blacks 61% and 63%, Hispanics 7% and 9%, and current smokers 28% and 43%. Median weight, body mass index, and waist circumference were similar in the two groups.
After statistical adjustment for baseline marker levels, smoking, male sex, and age, levels of two markers, the inflammation flag hsCRP and the macrophage activation signal sCD163 (which is associated with MAFLD) fell significantly in 32 weeks: 39.9% for hsCRP and 12.3% for sCD163. Levels of the inflammation marker IL-6 dropped 18.8%, but that fall did not reach statistical significance. Changes in hsCRP did not correlate with changes in weight or abdominal visceral adipose tissue, findings that indicate hsCRP trimmed marker levels independently of changes in weight or central fat. No other markers measured (sTNFR-I, sTNFR-II, sVCAM-1, D-dimer) changed significantly with semaglutide.
The investigators proposed that semaglutide may have value in treating lipohypertrophy and inflammation in people taking ART. But they cautioned that the drug’s impact on lean body mass may limit its use in some people.
1. Eckard AR, Wu Q, Sattar A, et al. Effects of semaglutide on inflammation and immune activation in HIV-associated lipohypertrophy. CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver. Abstract 798.
2. McComsey GA, Sattar A, Albar Z, et al. Effects of semaglutide on adipose tissue in HIV-associated lipohypertrophy. Open Forum Infect Dis. 2023;10(suppl 2). https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.111/7447334