The Effects of Semaglutide on Inflammation and Immune Activation in HIV-associated Lipohypertrophy.

Background: Cardiovascular and metabolic comorbidities are common in people with HIV (PWH) and are linked to chronic inflammation and immune activation. We assessed the effects of semaglutide on plasma markers of immune activation/inflammation that are known to be increased in PWH and are associated with morbidity and mortality in this population.

Methods: We conducted a single-site, randomized, double-blinded, placebo-controlled trial of virologically suppressed, nondiabetic PWH ≥18 years of age on stable antiretroviral therapy with body mass index ≥ 25 kg/m², increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after antiretroviral therapy initiation (clinicaltrials.gov: NCT04019197). Participants were randomized 1:1 to 32 weeks of semaglutide (8-week titration + 24 weeks of 1.0 mg weekly subcutaneous injection) or matching placebo. Signed-rank tests were used to determine changes over 32 weeks in soluble markers and cellular phenotypes of inflammation/immune activation within groups; semaglutide effects were assessed using linear or quantile regression analyses.

Results: A total of 108 participants were enrolled and evenly randomized to semaglutide versus placebo. Eight (15%) in each group withdrew prematurely. Thirty-two weeks of semaglutide treatment reduced baseline levels of C-reactive protein, interleukin-6, and soluble CD163 (all P < .02) and trended to reduce levels of sCD14 (P = .08). Circulating monocyte proportions and T-cell phenotypes were not altered by semaglutide.

Conclusions: In this randomized controlled trial of semaglutide in PWH, we report significant decreases in markers of inflammation that are associated with morbidity and mortality in this population. These results add to the growing literature demonstrating the anti-inflammatory effects of semaglutide. Further studies in PWH are warranted.