CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

873

Senescence-Associated Secretory Phenotype Biomarker Profiles of Age-Related Outcomes in PWH Mary C. Masters 1 , Janeway Granche 2 , Raha M. Dastgheyb 3 , Katherine Tassiopoulos 2 , Alan Landay 4 , Carrie Johnston 5 , Susan Koletar 6 , George A. Kuchel 7 , James L. Kirkland 8 , Tamar Tchkonia 8 , Kristine M. Erlandson 9 , Frank Palella 10 , for the ACTG A5322 (HAILO) Study Team 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 University of Texas Medical Branch, Galveston, TX, USA, 5 Weill Cornell Medicine, New York, NY, USA, 6 The Ohio State University, Columbus, OH, USA, 7 University of Connecticut Health Center, Farmington, CT, USA, 8 City of Hope, Duarte, CA, USA, 9 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 10 Northwestern University, Chicago, IL, USA Background: Cellular senescence is associated with age-related disease and has been a proposed mechanism in aging people with HIV (PWH) who may experience accelerated aging. We sought to characterize associations between pro-inflammatory signals secreted from senescent cells (the senescence associated secretory phenotype [SASP]), and age-associated outcomes. Methods: Clinical aging outcomes of frailty, cognitive impairment (CI), diabetes mellitus (DM), and cardiovascular disease (CVD) were collected at entry in the observational ACTG A5322 (HAILO) study of PWH ≥40 years old. There were 71 soluble SASP biomarkers measured from 450 HAILO participants at study entry. Sample selection prioritized participants with prevalent or incident outcomes for the current and ongoing analyses. Cross-sectional logistic models adjusting for age group (40-49, 50-59, 60+), sex, and race/ethnicity were run for each normalized SASP biomarker with each age-related outcome. False discovery rate (FDR) correction was performed to adjust for multiple comparisons. Results: Of the 450 participants, 59 (13%) met criteria for frailty, 104 (23%) CI, 94 (21%) DM, and 52 (12%) CVD at study entry. Participant ages: 36% were 40-49, 45% were 50-59, 19% were 60+; 78% were men; 48% were White non-Hispanic, 27% Black non-Hispanic, 24% any race. The Figure summarizes the 31 SASP biomarkers significantly associated with at least one outcome after FDR correction. Higher levels of TNFR1 were associated with higher odds of all outcomes; higher MMP-7, IL-6, TNFR2 and MCP-3b with higher odds of frailty, CI, and DM; higher levels Cystatin C with higher odds of frailty, DM, and CVD. After FDR adjustment, no biomarkers were associated with frailty alone. Higher levels of sVCAM-1, MMP1, TIMP-2, IP-10, activin A, and IL-18 were associated with higher odds of CI; higher levels of IGF-1 with lower odds of CI; higher levels of PAI1, and osteoactivin with higher odds of DM; higher levels of adiponectin and ACRP30 HMW with lower odds of DM; and higher levels of MMP-9, suPAR, and VEGF-A with higher odds of CVD. Conclusions: Unique SASP profiles exist in association with specific aging outcomes in PWH, with some overlap between conditions apparent; this may indicate shared pathophysiologic mechanisms among the outcomes. Additional studies will determine whether such biomarker profiles also predict subsequent development of age-related outcomes, offering insights into premature aging mechanisms and therapeutic targets to improve healthspan among older PWH.

874

Multicomponent Exercise Associated With a Healthier Gut Microbiota Profile in Older Adults With HIV Laura Martín Pedraza 1 , Fátima Brañas 2 , Fernando Dronda 1 , Laura Luna 1 , Pablo Ryan 2 , Santiago Moreno 1 , Marta Martínez 2 , Matilde Sánchez-Conde 3 1 Hospital Universitario Ramon y Cajal, Madrid, Spain, 2 Hospital Universitario Infanta Leonor, Madrid, Spain, 3 Hospital Ramón y Cajal, Madrid, Spain Background: Multicomponent Exercise has been shown to modulate the gut microbiota leading to changes that may contribute to a less inflammatory and more eubiotic microbial profile. However, there is limited evidence on the effects of exercise on the gut microbiota in older adults living with HIV (OAWH). In this 48-week longitudinal study, we evaluated the changes in the gut microbiota through metagenomic whole genome shotgun (mWGS) sequencing of participants after undergoing 48 weeks of a Multicomponent Exercise Program (MEP). Methods: Sedentary adults aged 50 and over, with and without HIV, were included in a prospective longitudinal study with intervention, a MEP, and with 12-, 24- and 48-week follow-up. Clinical variables were obtained as well as adherence to the MEP defined as good (>50%) or poor (<50%). Stool samples were collected at each visit. We performed mWGS sequencing of 129 faeces DNA and analysed the taxonomy and functional annotation by Metastats and LEfSe analysis. Results: We included 60 participants, 40 OAWH. Median age was 56.5 years. 23.3% were women. All participants with HIV were virologically controlled. At baseline, significant differences in the gut microbiota composition were observed when comparing different groups: a relative abundance of Firmicutes , Prevotella , and Dialister was significantly higher in men compared to women (p<0.05) and similarly, Catenibacterium was found to be increased in older adults with HIV (OAWH) (p<0.05). Furthermore, we globally observed high relative abundance of some genus related with inflammation and obesity as Collinsella spp . (p<0.05) ( Figure 1A ). Finally, according to changes of relative abundances, differences after 48 weeks of MEP highlighted a significant increase in bacterial genus such as Bacteroides , Prevotella , and Bifidobacterium and significant decrease of Coriobacteriaceae ( Figure 1B ). These genera play a crucial role in the production of short-chain fatty acids and immune regulation. Conclusions: A MEP could positively modulate the gut microbiota in OAWH potentially promoting a healthier and less inflammatory microbial environment. This highlights the potential role of regular physical activity as a strategy to improve gut health and overall well-being in older populations, regardless of HIV status. The figure, table, or graphic for this abstract has been removed. Muscular Markers for Early Identification of Sarcopenia and Frailty States in Older People With HIV Eugènia Negredo 1 , Irini Sereti 2 , Ana Martinez 1 , Sandra González 3 , Jordi Puig 1 , Gemma Monté-Rubio 4 , Adam Rupert 5 , Patricia Echeverria 1 , Anna Bonjoch 1 , Josep Puig 4 , Diana Hernandez 6 1 Fundació Lluita contra les Infeccions, Barcelona, Spain, 2 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 3 Hospital Germans Trias i Pujol, Barcelona, Spain, 4 Comparative Medicine & Bioimage Centre of Catalonia (CMCiB), Barcelona, Spain, 5 Frederick National Laboratory for Cancer Research, Frederick, MD, USA, 6 Fundació Lluita contra la SIDA, Badalona, Spain Background: Considering the critical need to identify people with HIV (PWH) at risk of frailty and sarcopenia, we present the results of the Functional substudy of the IMAGING study, a study aimed to identify image aging markers by whole-body magnetic resonance imaging (WB-MRI) in 50 PWH aged 50 years or older and 25 matched controls. Methods: The Functional substudy is an exploratory study that evaluates WB-MRI muscle markers (intramuscular fat content in glutes, psoas, iliac, and total muscle) and specific muscular (irisin and myostatin) and mitochondrial (coenzyme Q10) plasma biomarkers for diagnosing pre-frailty/frailty or sarcopenia in PWH. Imaging, from the WB-MRI data collected in a Vantage Galan 3T (Canon Medical Systems, Japan) at the CMCiB, and muscle biomarkers were compared between PWH and controls, and correlated with functional evaluations (Barber, Barthel, Lawton, Fried phenotype, SPPB and grip strength) and DXA scan. Statistical analyses were performed using R software (https:// www.r-project.org/). The protocol was approved by the Ethics Committee [Reference no. PI-20-035]. Results: Median duration of HIV infection was 29 years; all had undetectable viral loads. PWH had more comorbidities (median 5 vs. 3); 50% of PWH and 28%

Poster Abstracts

875

CROI 2025 269