Background:
Lipohypertrophy (central adipose tissue (AT) accumulation) is a common and significant problem in people with HIV (PWH). We previously demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, significantly decreased central AT in PWH with lipohypertrophy, primarily driven by reductions in visceral AT. Here, we assessed the effects of semaglutide on inflammation and immune activation biomarkers, known to be increased in PWH and associated with cardiovascular disease (CVD).
Methods:
We conducted a single-site randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥25 kg/m², increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Sign-rank test was used to determine changes over 32 weeks in soluble markers of inflammation/immune activation within groups; semaglutide effects were assessed using generalized estimating equations.
Results:
108 participants were enrolled (N=54 semaglutide: median age=52 years, 70% male, 61% Black, 83% integrase inhibitor). Groups were well-matched in demographics and BMI at baseline. Significant changes within semaglutide group were seen between baseline and week 32 geometric means (standard deviation) for interleukin-6 (IL-6) [2.51 (2.05), 2.13 (1.85) pg/mL; P=0.016], high-sensitivity C-reactive protein (hsCRP) [2.98 (2.69), 1.83 (2.96) µg/mL; P=0.008] (Figure 1), and sCD163 [583 (1.48), 511 (1.54) ng/mL; P=0.005] with a trend in sCD14 [1694 (1.3), 1575 (1.28) ng/mL; P=0.085]. No significant changes were observed for soluble intercellular adhesion molecule-1 (sICAM-1) or TNF-receptor-I/-II. Biomarker levels did not change significantly within the placebo group. Treatment effects of semaglutide were significant in regression analyses (β coefficient [95% confidence interval]) for log IL-6 (-0.30 [-0.54, -0.06]; P=0.015) and log hsCRP (-0.51 [-0.90, -0.12]; P=0.011) with trends in log sCD14 (-0.08 [-0.18, 0.01]; P=0.083) and log sICAM-1 (-0.11 [-0.24, 0.02]; P=0.088).
Conclusions:
In non-diabetic PWH with lipohypertrophy, semaglutide had significant effects on several key biomarkers associated with CVD in HIV. Further investigation is warranted to determine the effect on co-morbidities in HIV.
