CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

861

Cardiometabolic Effects of Semaglutide in People With HIV: The SLIM LIVER Study Jordan E. Lake 1 , Doug Kitch 2 , Amy Kantor 2 , Raja Muthupillai 3 , Pablo Belaunzarán Zamudio 4 , Carl Fichtenbaum 5 , Hugo Perazzo 6 , Sonya L. Heath 7 , Todd Brown 8 , Alan Landay 9 , Jennifer Kinslow 10 , Fred R. Sattler 11 , Kristine M. Erlandson 12 , for the ACTG A5371 Protocol Team 1 University of Texas Health Science Center at Houston, Houston, TX, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 ForeSpect PLLC, Pearland, TX, USA, 4 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 5 University of Cincinnati Medical Center, Cincinnati, OH, USA, 6 Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, 7 University of Alabama at Birmingham, Birmingham, AL, USA, 8 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 9 University of Texas Medical Branch, Galveston, TX, USA, 10 Rush University, Chicago, IL, USA, 11 University of Southern California, Los Angeles, CA, USA, 12 University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: The glucagon-like peptide-1 receptor agonist semaglutide (SEMA) reduces weight and inflammation in the general population. We previously reported reductions in weight (mean -7.8 kg, 95% confidence interval, [CI, -9.5, -6.1]), insulin resistance (IR), serum triglycerides and liver fat in people with HIV (PWH) receiving SEMA in ACTG A5371, the SLIM LIVER study. Here we report additional metabolic, fat imaging and inflammatory marker endpoints, including follow-up after SEMA discontinuation. Methods: ACTG A5371 enrolled PWH >/=18 years old on suppressive antiretroviral therapy (ART) with metabolic dysfunction-associated steatotic liver disease. All received low-dose, subcutaneous (sc) SEMA 1mg weekly for 24 weeks (W) followed by 24 W off SEMA. Biomarker/immune profiles and magnetic resonance imaging (MRI) were available at W 0 and 24, and other measures at W 0, 24 and 48. Mean (95% CI) changes were estimated using linear regression and risk estimates by a log link GEE model (a=0.05) Results: PWH (n=49) had: median age 52 years, BMI 35 kg/m 2 , 39% Hispanic ethnicity, 33% Black/African American race, 43% cis/trans female and 82% INSTI-based ART. 24 W of SEMA was associated with a 25% reduction in metabolic syndrome risk and reduced visceral (-13%) and abdominal sc (-12%) fat by MRI (all p<0.05). A trend towards improvement in the frequency of elevated alanine aminotransferase (ALT, a steatohepatitis surrogate) occurred in women (women: 68% to 42%, p=0.06; men: 43% to 41%). Significant changes in adiponectin ( ↑ ), leptin ( ↓ ) and CRP ( ↓ ) were observed, with no change in IL-6 or monocyte/T cell profiles (data not shown). After 24 W off SEMA (Fig.), absolute weight regain was +2.9 kg (1.5, 4.3), with women, White non-Hispanics and PWH <40 years of age regaining more. Among those who lost and regained weight (n=31), 75% of lost weight was regained. Weight regain was accompanied by significant increases in waist circumference (2.0 cm [0.9, 3.1]) and fasting glucose (5.1 mg/dL [0.9, 9.3]) without significant short-term changes in blood pressure, total or LDL cholesterol, triglycerides or metabolic syndrome. Elevated ALT frequency increased (women: 42% to 59%; men: 41% to 54%). Conclusions: Short-term, low-dose SEMA was associated with cardiometabolic benefit in PWH. Rapid weight regain and some loss of cardiometabolic benefit occurred off SEMA, similar to the general population. Further study of higher dose SEMA and strategies to maintain benefits of SEMA following initial therapy are needed in PWH. The figure, table, or graphic for this abstract has been removed. Durability of Semaglutide Effects After Drug Discontinuation in HIV-Associated Lipohypertrophy Allison Ross Eckard 1 , Qian Wu 2 , Abdus Sattar 2 , Kianoush Ansari-Gilani 3 , Danielle Labbato 3 , Corrilynn O. Hileman 4 , Aaron A. Fletcher 3 , Grace A. McComsey 2 1 Medical University of South Carolina, Charleston, SC, USA, 2 Case Western Reserve University, Cleveland, OH, USA, 3 University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 4 MetroHealth Medical Center, Cleveland, OH, USA Background: Lipohypertrophy (central adipose tissue (AT) accumulation) and AT abnormalities are common in people with HIV (PWH) and are key drivers of cardiometabolic co-morbidities. In a recent randomized, double-blind, placebo-controlled phase 2b clinical trial, we observed significant effects of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), semaglutide, over 32 weeks on key outcome measures, including reductions in weight, total body fat, and visceral adiposity in people with HIV-associated lipohypertrophy. The current analysis investigates the durability of semaglutide effects 24 weeks after drug discontinuation.

Methods: Virologically-suppressed PWH without known diabetes on stable antiretroviral therapy with body mass index ≥25 kg/m 2 and increased waist circumference/waist-to-hip ratio were included. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly nurse-administered subcutaneous injection) or matching placebo (intervention phase). Drug discontinuation occurred at week 32; outcome measures were reassessed at week 56 (post-interventional phase). Analyses were performed with intention-to-treat principles using sex-adjusted multiplicative regression modeling. Results: 108 participants (N=54 semaglutide) were enrolled (median age: 53 years; 60% male); 16 and 12 participants withdrew before week 32 and 56, respectively. Some residual semaglutide effects remained but were no longer statistically significant at week 56 (24 weeks after discontinuation) in key outcome measures (Figure 1). Semaglutide effects for weight, total body fat, abdominal visceral AT, and abdominal subcutaneous AT showed decreases from baseline of -5%, -12%, -16%, and -3% at week 56 (all p>0.05) vs. -10%, -20%, -32%, and -12% at week 32 (all p≤0.01), respectively. Improvements in glucose metabolism observed at 32 weeks were no longer evident at week 56 (0% and -1% at week 56 vs. baseline for hgbA1c and fasting glucose, respectively). Among 24 of 39 (62%) participants in the semaglutide group who lost ≥5% body weight during the intervention phase and completed week 56, 12 (50%) regained half to all the weight. Conclusions: Much of the positive semaglutide effects achieved over 32 weeks was reversed after 24 weeks off drug. Apparent lack of durability with GLP-1 RA treatment in PWH raises concern for prolonged treatment requirements. Larger trials, particularly those assessing safety with higher doses and longer GLP-1 RA use, are needed in HIV. The figure, table, or graphic for this abstract has been removed. Impact of Antidiabetic Medications on Weight Change Among People With HIV Lara Haidar 1 , Robin M. Nance 2 , Bridget M. Whitney 2 , Stephanie A. Ruderman 2 , Allison Webel 2 , Geetanjali Chander 2 , Amanda Willig 3 , Edward Cachay 4 , Kenneth Mayer 5 , Jeffrey M. Jacobson 6 , Richard Moore 7 , Lydia N. Drumright 2 , Heidi M. Crane 2 , Joseph A. Delaney 2 , Sherif Eltonsy 1 , for the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) 1 University of Manitoba, Winnipeg, Canada, 2 University of Washington, Seattle, WA, USA, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 University of California San Diego, La Jolla, CA, USA, 5 The Fenway Institute, Boston, MA, USA, 6 Case Western Reserve University, Cleveland, OH, USA, 7 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: While novel antidiabetic medications like glucagon like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated weight loss in the general population, data on their impact on weight loss in PWH remains limited. Methods: We identified adult PWH in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort who initiated GLP-1RAs, SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP4is), or sulfonylureas between 1996-2023 who had ≥2 weight measurements available, including 1 prior to and ≥1 post medication initiation. The primary outcome evaluated was percent weight change at 1 year, analyzed using a linear mixed model. We also assessed whether the effect of GLP-1RAs and SGLT2is on weight change varied by diabetes status. The secondary outcome evaluated, time to ≥5% weight loss, was analyzed using a Cox proportional hazards model. Both models were adjusted for relevant demographic and clinical characteristics. Results: Overall, 2086 patients met inclusion criteria, with 638 on GLP1-RA, 295 on SGLT2i, 219 on DPP4i, and 934 on sulfonylureas. Mean age at baseline was 52 years (SD: 10), 25% were female, and 47% were Black. At baseline, average weight was 98 kg (SD:25), 83% had diabetes, and 92% were on antiretroviral therapy. In adjusted analyses, percent weight change was significantly greater for GLP-1RAs (-4.13; 95%CI: -4.99, -3.28) compared to SGLT2is (-2.50; 95%CI: -3.72, -1.28), DPP4is (-0.57; 95%CI: -1.49,0.35), and sulfonylureas (-0.49; 95%CI: -1.11,0.13) (interaction p values all <0.05; see Figure). Among PWH on GLP-1RAs, those without diabetes experienced greater percent weight loss (-5.39; 95%CI: -7.20, -3.58) compared to those with diabetes (-3.56; 95%CI: -4.50, -2.62), although the interaction p-value was not significant (p=0.08). Conversely, SGLT2is trended towards a greater percent weight loss for those with diabetes (-3.23; 95%CI: -4.45, -2.00) compared to those without (-0.86; 95%CI: -3.53,1.80), however this interaction p-value was also non-significant

Poster Abstracts

863

862

CROI 2025 264