CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

799

Effects of Semaglutide on Muscle Structure and Function in the SLIM Liver Study Grace L Ditzenberger 1 , Jordan E. Lake 2 , Douglas W. Kitch 3 , Amy Kantor 3 , Raja Muthupillai 4 , Pablo Belaunzaran-Zamudio 5 , Todd T. Brown 6 , Kathleen Corey 7 , Alan Landay 8 , Anchalee Avihingsanon 9 , Fred R. Sattler 10 , Kristine M. Erlandson 1 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 University of Texas at Houston, Houston, TX, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Baylor College of Medicine, Houston, TX, USA, 5 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 6 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 7 Massachusetts General Hospital, Boston, MA, USA, 8 Rush University, Chicago, IL, USA, 9 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 10 University of Southern California, Los Angeles, CA, USA Background: Semaglutide, a GLP-1 receptor agonist, is a highly effective medication for decreasing weight and weight complications by suppressing appetite, improving insulin signaling, and reducing intrahepatic triglycerides (IHTG). However, concomitant loss of muscle mass often accompanies weight loss, which may have consequences on muscle function. The purpose of this analysis was to examine changes in muscle quality, quantity, and function among people with HIV (PWH) treated with semaglutide for metabolic associated steatotic liver disease (MASLD). Methods: We leveraged data from the SLIM LIVER (ACTG A5371) study, a single arm pilot of the effects of semaglutide on IHTG in PWH with MASLD. Participants received subcutaneous semaglutide for 24 weeks (titrated to 1 mg/week by week 4). Psoas volume/fat fraction were assessed from liver magnetic resonance imaging and physical function by 10-time chair rise test and 4m gait speed, at baseline and week 24. Mean change from baseline was estimated with linear regression modeling and associations with Spearman's correlations. Results: 51 PWH enrolled; muscle measures were available from 46 participants. The mean age was 50 (standard deviation [SD] 11) years and BMI 35.5 (5.6) kg/m², 43% were women, 33% Black, and 39% Hispanic/Latino. Psoas muscle volume decreased by 9.3% (95% confidence interval [CI]: -13.4, -5.2; p<0.001) with an overall mean weight loss of -7.8 kg (CI: -9.5, -6.2) over 24 weeks. Decreases in psoas volume were greatest among PWH >60 years old (-22.8% [CI: -32.4, -13.3] vs -7.9% [CI: -12.3, -3.4]) in 40-60 and -2.4% [CI: -11.9, 7.2] in <40). No sex differences were observed. Reductions in psoas volume (%) correlated with decreases in IHTG (ρ=+0.32, p=0.028), BMI (ρ=+0.31, p=0.038), HbA1C (ρ=+0.39, p=0.007), and reduction in absolute volume was associated with reduction in fasting triglycerides (ρ=+0.33, p=0.027). Psoas muscle fat decreased by 0.42% (CI: -1.00, 0.17; absolute change), chair rise time improved by 0.73 seconds (CI: -1.4, 2.9) and gait speed improved by 0.05 m/sec (CI: -0.01, 0.10), though these changes did not reach statistical significance (p>0.078). The prevalence of slow gait speed (<1m/sec) decreased from 63% to 46% (p=0.029). Conclusion: In PWH using low-dose semaglutide for MASLD, muscle volume decreased, similar to volume changes seen in weight-loss interventions among overweight populations. The observed average improvement in muscle function suggests a beneficial effect of semaglutide on overall muscle quality. A Combination of Steatosis-Fibrosis Index Predict Mayor Cardiovascular Events in PLHIV María Luisa Montes, Carmen Busca, Antonio Olveira, Jose I Bernardino , Luz Martín-Carbonero, Marta Abadia, Eulalia Valencia, Rafael Mican, Rocio Montejano, Rosa De Miguel Buckley, Jose R. Arribas, Juan González-García La Paz University Hospital, Madrid, Spain Background: Metabolic dysfunction-Associated Steatosis Liver Disease (MASLD) is a high prevalent condition in people living with HIV (PLHIV) and cardiovascular events appear to depend on the presence of advanced stages of MASLD. Indeed, the underlying insulin resistance and liver fibrosis have demonstrated complex interlinked connections affecting cardiovascular damage evolution. Our objective is to analyze the usefulness of two easy-to-use surrogate biomarkers of insulin resistance and liver fibrosis in the prediction of major cardiovascular events (MACE) in PLHIV. Methods: A retrospective cohort of PLHIV receiving ART with metabolic disorders (metabolic syndrome, DM2, arterial hypertension, and obesity) and clinically suspected MASLD was studied. We recorded all MACE occurring during follow-up, and we calculated TyG and FIB-4 indexes from the blood results performed at the initial visit in the cohort. TyG>4.68 was considered as severe insulin resistance risk. FIB-4 cut-off values considered for significant fibrosis were adjusted by hepatitis C virus (HCV) coinfection background: >1.3 for non hepatitis C and >1.45 for HCV coinfected. TyG>4.68 plus FIB-4>1.3/1.45 was

798

Effects of Semaglutide on Inflammation and Immune Activation in HIV-Associated Lipohypertrophy Allison Ross Eckard 1 , Qian Wu 2 , Abdus Sattar 2 , Nicholas Funderburg 3 , Kate Ailstock 3 , Danielle Labbato 4 , Grace A. McComsey 2 1 Medical University of South Carolina, Charleston, SC, USA, 2 Case Western Reserve University, Cleveland, OH, USA, 3 The Ohio State University, Columbus, OH, USA, 4 University Hospitals Cleveland Medical Center, Cleveland, OH, USA 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). Conclusion: 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.

Poster Abstracts

800

CROI 2024 241

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