CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

of controls had over 5 comorbidities. Malnutrition risk was higher in PWH (31% vs. 13.6%). A higher prevalence of dependency, prefrailty/frailty and low bone mineral density (BMD) were observed among PWH, as well as higher plasma levels of myostatin and lower levels of irisin (Table 1). Higher Coenzyme Q10 levels were associated with poorer health (dependency, frailty, osteopenia/ osteoporosis); high irisin levels with frailty and dependency; and lower myostatin levels with poorer health, though some contradictory data were noted. Lower intramuscular fat fractions were observed in malnutrition and less so in conditions like dependency. Associations were found between higher intramuscular fat content and time of infection, time on antiretroviral therapy and time until therapy; while a better immunological status was associated with lower fat content. Conclusions: In summary, PWH showed overall more dependency and frailty compared to controls with more unfavorable accompanying plasma markers. Thus, specifically irisin and Coenzyme Q10, might be potential diagnostic markers for dependency and frailty, if larger studies support their clinical utility potential. These results encourage us to continue assessing these markers for their predictive and diagnostic potential.

without statistically significant differences. Linear mixed models showed a similar evolution between groups in EAA. A trend towards a potential effect on DNAmTL was observed with Wilcoxon ( p = 0.077), although this was not confirmed by linear mixed model. Conclusions: In this pilot trial, metformin treatment for 96 weeks was safe and well-tolerated in PWH without diabetes. While no trend favoring metformin was observed across the epigenetic clocks analyzed, the trend in DNAmTL suggests a potential positive biological effect, warranting further investigation in larger studies.

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Statins Reduce Frailty in People With HIV Jovana Milic 1 , Alessandra Carrobbio 1 , Marianna Menozzi 2 , Giuseppe Mancini 1 , Gianluca Cuomo 2 , Federico Motta 1 , Chiara Mussi 1 , Cristina Mussini 1 , Paolo Raggi 3 , Giada Sebastiani 4 , Giovanni Guaraldi 1 1 University of Modena and Reggio Emilia, Modena, Italy, 2 AOU Policlinico di Modena, Modena, Italy, 3 University of Alberta, Edmonton, Canada, 4 McGill University Health Centre, Montreal, Canada Background: Statins have pleiotropic effects beyond lowering LDL cholesterol, offering benefits in multiple cardiometabolic conditions and reducing chronic inflammation. These effects have the potential to also influence biological aging trajectories, reflected by frailty. The objective of this study was to compare frailty trajectories, in people with HIV (PWH) who used statins for primary cardiovascular prevention with those who did not. Methods: This was an observational longitudinal study including antiretroviral therapy (ART)-experienced PWH attending the Modena HIV Metabolic Clinic (Italy) who had no prior statin exposure at baseline (BL) and with at least 3 frailty assessments during follow-up. PWH with a history of cardiovascular events were excluded. BL was defined as the first visit with available FI, and follow-up was defined as the last visit with available FI. Statin users and non-users were matched based on median time between BL and initiation of the statin therapy in the first group. Time 0 was defined as the initiation of the statin therapy. Frailty was assessed using a validated 37-item frailty index (FI), ranging from 0 to 1. Frailty trajectories were analysed using a linear mixed model (LMM) adjusted for statin use, age, sex, follow-up time, diabetes, hypertension, smoking (pack year), and BL LDL cholesterol. Results: A total of 3,543 PWH were included, 1,100 (31%) were women. The median age at BL was 44.7 yrs, median time since HIV diagnosis was 14 yrs, median current CD4 cell count was 558.5/microL with 88.6% having undetectable HIV viral load. At BL, PWH who started statin were older (48.4 vs 43.6 yrs, p<0.001), had a higher: FI (0.3 vs 0.2; p<0.001), BMI (23.9 vs 23 kg/ m2; p<0.001), LDL cholesterol (129 vs 109 mg/dL; p<0.001), prevalence of hypertension (31.8 vs 15.4%; p<0.001), diabetes (11.5 vs 4.7%; p<0.001). In LMM, statin use (β= -0.0171, 95% confidence interval (CI): -0.0345, -0.0009) was a significant predictor of FI reduction (Figure 1). Other factors associated with FI were: female sex (β= -0.0123, 95% CI: -0.0194, -0.0052), diabetes (β= 0.0305, 95% CI: -0.0248, 0.0362), hypertension (β=0.0389, 95% CI: 0.0349, 0.0429). Conclusions: Statin use significantly reduces frailty over time. Although PWH who started statins had a higher FI at baseline, they were able to reverse the BL difference, reaching a lower FI compared to the control group by the end of follow-up. These findings suggest that statins may have a geroprotective effect in PWH.

Poster Abstracts

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Metformin for Reversal of Accelerated Biological Aging in Persons With HIV: A Pilot Clinical Trial Cristina Marcelo 1 , Andrés Esteban-Cantos 1 , Francisco Jurado 2 , Javier Rodríguez Centeno 3 , Rocío Montejano Sanchez 1 , Lucía Gutiérrez 3 , Alejandro de Gea Grela 3 , Patricia Martínez-Martín 1 , Juan Carlos González 3 , Luz Martín-Carbonero 1 , Jose Ignacio Bernardino 3 , Berta Rodés 3 , Jose R. Arribas 3 1 Hospital Universitario La Paz, Madrid, Spain, 2 Centro Nacional de Investigaciones Oncológicas, Madrid, Spain, 3 Hospital La Paz Institute for Health Research, Madrid, Spain Background: There is interest in metformin as a drug to delay aging in the general population. This is the first trial to evaluate the impact of metformin on biological aging measured by epigenetic clocks with prognostic value in PWH. Methods: Phase II randomized, double-blind, pilot clinical trial comparing metfomin 850 mg BID vs placebo. Main inclusion criteria included age ≥ 50, HIV viral load < 50 for ≥ 1 year, CD4 > 500, HOMA-IR ≤ 2.6, BMI <30, and normal B12 vitamin levels. Key exclusion criteria included diabetes, comorbidities (stroke, heart failure, dementia, cancer or renal impairment) and pregnancy. Objectives were to assess metformin safety, changes in Epigenetic Age Acceleration (EAA) measured by Horvath, Hannum, PhenoAge, GrimAge, and DNAmfitAge epigenetic clocks in whole blood, and changes in blood telomere length measured by DNA methylation (DNAmTL) after 96 weeks of follow-up. EAA was calculated as the residuals from the regression of epigenetic age on chronological age. We compared changes between treatment groups using both linear mixed models with random intercepts and slopes and Wilcoxon signed-rank test. Results: We included 40 participants, of whom 35 (17 metfomin and 18 placebo) maintained their randomized treatment until week 96. Discontinuations were not attributed to adverse events related to the study medication. At baseline, groups were balanced, with a mean chronological age of 57 years, 30% female, BMI of 24.1, HOMA IR of 1.39, CD4 counts (current/ nadir) of 855/291 cells/µl, CD4/CD8 of 1.3, and with no differences in EAA measures and DNAmTL. Participants receiving metformin demonstrated a significant increase in serum GDF15, confirming metformin adherence. At week 96, there were no significant differences between groups in CD4 counts, and renal function, and all participants remained virologically suppressed. Median decreases in EAA were numerically larger in metformin for 3 of the 5 clocks,

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