CROI 2025 Abstract eBook

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Poster Abstracts

Conclusions: Metabolic disturbances linked to liver steatosis and CVD differ across BMI categories in PLHIV. Lean PLHIV with liver steatosis, unlike their overweight/obese counterparts, show common metabolic perturbation with future CVD events. This suggests a heightened CVD risk in lean PLHIV with liver steatosis, potentially opening avenues for interventions targeting the arachidonic acid metabolism, such as aspirin therapy, to mitigate this risk. The figure, table, or graphic for this abstract has been removed. Incidence and Impact of Hepatic Steatosis in People With HIV: Insights From the NA-ACCORD Cohort Jennifer Price 1 , Nina Kim 2 , Marina Klein 3 , Vincent Lo Re 4 , M. John Gill 5 , Michael Horberg 6 , Jennifer O. Lam 7 , Catherine Lesko 8 , Angel Mayor 9 , Richard Moore 8 , George Yendewa 10 , Giada Sebastiani 3 , for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Washington, Seattle, WA, USA, 3 McGill University Health Centre, Montreal, Canada, 4 University of Pennsylvania, Philadelphia, PA, USA, 5 University of Calgary, Calgary, Canada, 6 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA, 7 Kaiser Permanente Northern California, Oakland, CA, USA, 8 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 9 Universidad Central del Caribe, Bayamon, Puerto Rico, 10 Case Western Reserve University, Cleveland, OH, USA Background: Hepatic steatosis is an increasingly important comorbidity in aging people with HIV (PWH). Population-representative estimates of incidence, risk factors and association with liver-related events are not well understood. We evaluated the incidence of hepatic steatosis and its association with liver related events and overall mortality within the NA-ACCORD. Methods: Hepatic steatosis was defined using the hepatic steatosis index (HSI), a biomarker based on sex, liver aminotransferases, diabetes status, and body mass index. Steatosis was defined as an HSI >36. Adult PWH without viral hepatitis coinfection from 11 cohorts were followed from first HSI measurement after 1/1/2000 until first occurrence of a liver-related event (ascites, encephalopathy, variceal bleeding, or hepatorenal syndrome confirmed by adjudication), death, one year after last CD4 or HIV RNA, or 12/31/2015. We reported the incidence of and risk factors for hepatic steatosis and is association with liver-related events and overall mortality. Results: 20,903 PWH without viral hepatitis (mean age 39 yrs, 81% males) were included. The incidence rate (IR) of hepatic steatosis was 180 per 1000 person-years (PY) (95% CI 173-185). The IR was 188/1000 PY (95% CI 177-201) from 2000-2004, 206/1000 PY (95% CI 196-217) from 2005-2008, and 168/1000 PY (95% CI 162-174) from 2009-2015 (Figure). After adjusting for age, ethnicity, smoking, alcohol use, and dyslipidemia, hypertension was independently associated with a higher risk of hepatic steatosis (adjusted hazard ratio [adjHR] 1.41, 95% CI 1.22-1.62) as was antiretroviral therapy exposure (adjHR 1.09, 95% CI 1.02-1.16), and higher CD4 cell count was protective against hepatic steatosis (CD4 204-386: adjHR 0.85, 95% CI 0.78-0.93; CD4 387-585: adjHR 0.80, 95% CI 0.73-0.87; CD4 >585: adjHR 0.75, 95% CI 0.68-0.82). The IR of hepatic steatosis on liver-related events was 1.7/1000 PY (95% CI 1.5-2.0) and on death was 15.2/1000 PY (95% CI 14.4-15.9). Hepatic steatosis was not associated with liver-related events but was associated with overall mortality (adjHR 1.02, 95% 1.01-1.04), after adjusting for age, ethnicity, smoking, alcohol use, CD4 cell count, dyslipidemia, and hypertension. Conclusions: Hepatic steatosis was prevalent among PWH in this large North American cohort but did not increase the risk of liver-related events. However, its association with overall mortality underscores the need for further research into the long-term health implications of hepatic steatosis in PWH.

demonstrated beneficial effects of semaglutide on gut microbiota profiles and improved disease outcomes, though the effects on human gut microbiota are unknown. We previously demonstrated that semaglutide was highly effective in improving MASLD for PWH. Here we investigated the effects of semaglutide on the gut microbiome within that cohort. Methods: SLIM LIVER, a single-arm, pilot study enrolled PWH ≥18 years old on suppressive antiretroviral therapy (ART) with MASLD. Participants received semaglutide 1 mg/week subcutaneously for 24 weeks. 16S rRNA and shotgun metagenomic sequencing was performed on stool collected at Weeks (W) 0 and 24. The treatment effects on microbiota were analyzed using generalized linear mixed modeling accounting for age, race/ethnicity, and gender identity (other demographic/clinical variables were not associated with microbiota at W0). Results: 51 people were enrolled; paired W0 and 24 stool samples were available from 42 participants (mean age 49 years, [SD 11]; BMI 35.4 [5.9] kg/m 2 ; 35% cis and 7% trans female; 31% Black; 38% Hispanic/Latino; 79% on INSTI-based ART). Overall microbiota composition (β-diversity; GLMM MiRKAT) differed between W0 and 24 at genus (P=0.002) and species levels (P=0.011). α-diversity increased (Shannon H, P=0.0075) over 24 weeks. Relative abundances of bacterial genera Clostridium and Enterococcus increased significantly (FDR<0.05). Anaerostipes , Ruminococcus-torques-group , and Lachnoclostridium significantly decreased. Metagenomic analysis identified an increase in Methanobrevibacter sp. (domain Archaea) over time (nominal p<0.05). Conclusions: We provide first-in-human evidence that use of semaglutide alters gut microbiota profiles in PWH with MASLD. Potentially beneficial effects included increasing diversity and abundance of genera (e.g. Methanobrevibacter ) where low abundance was associated with MASLD pathogenesis in people without HIV. However, we observed decreases in some bacteria (e.g. Lachnoclostridium ) where low abundance was previously associated with MASLD in other populations. Thus, semaglutide treatment in PWH with MASLD had a range of impact on microbiota abundance. Distinct Metabolic Perturbations Link Liver Steatosis and Incident CVD in Lean but Not Obese PLHIV Nadira Vadaq 1 , Louise E. van Eekeren 1 , Marc J. T. Blaauw 2 , Albert L. Groenendijk 3 , Wilhelm A. Vos 4 , Erni Nelwan 5 , Janneke Stalenhoef 4 , Marvin Berrevoets 2 , Mihai G. Netea 1 , Gert Weijers 1 , Joost Rutten 1 , Quirijn de Mast 1 , Eric Tjwa 1 , Leo Joosten 1 , for the 2000HIV Human Functional Genomics Partnership Program 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands, 3 Erasmus University Medical Center, Rotterdam, Netherlands, 4 OLVG, Amsterdam, Netherlands, 5 University of Indonesia, Jakarta, Indonesia Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a key risk factor for cardiovascular disease (CVD), potentially driven by shared metabolic mechanisms. However, the metabolic perturbations linking MASLD and CVD remains unexplored in people living with HIV (PLHIV). Methods: We investigated subjects from the longitudinal multicenter 2000HIV study (NCT03994835), which included 1895 virally suppressed PLHIV on antiretroviral treatment. Of these, 970 participants had liver measurements. Liver steatosis (CAP > 263 dB/m) and fibrosis (LSM ≥ 7.0) were assessed using transient elastography with the controlled attenuation parameter (CAP). CVD history and new incidents within a two-year follow-up, including myocardial infarction, stroke, peripheral arterial disease, and angina, were extracted from medical records, while carotid artery plaques were assessed via ultrasonography. Mass spectrometry-based untargeted metabolomics (n=500 metabolites) and nuclear magnetic resonance spectroscopy for targeted lipoproteomics (n=246 metabolites) were used to analyze metabolic perturbations linked to MASLD and CVD. Results: PLHIV with liver steatosis were more likely to have arterial plaques (47% vs. 36%; P-value = 0.003) and CVD history (11% vs. 6.8%; P-value = 0.021) than PLHIV without liver steatosis. These associations were more pronounced in lean PLHIV compared to those with BMI ≥ 25 kg/m 2 . Metabolic pathways associated with liver steatosis and fibrosis primarily involved lipid and amino acid metabolism (Figure 1); a finding validated by targeted lipoproteomic measurements. Notably, metabolomic pathways and lipoproteomic signatures associated with MASLD were mostly distinct from those associated with CVD parameters. However, several pathways were shared, especially in lean PLHIV (Figure 1), including arachidonic acid metabolism and formation of prostaglandin, purine metabolism, cholecalciferol metabolism, and glycine, serine, alanine- and threonine metabolism.

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