CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

836

Biomarkers of Microbial Translocation and Inflammation Associated With Frailty Among People With HIV Stephanie A Ruderman 1 , Peter W. Hunt 2 , Amanda Willig 3 , Michael S. Saag 3 , Sonia Napravnik 4 , Edward Cachay 5 , Laura Bamford 6 , Lydia N. Drumright 1 , Lyndsey S. Mixson 1 , Bridget Whitney 1 , Robin M. Nance 1 , Mari Kitahata 1 , Heidi M. Crane 1 , Joseph A. Delaney 1 , Andrew Hahn 1 1 University of Washington, Seattle, WA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 University of California San Diego, San Diego, CA, USA, 6 University of California San Diego, La Jolla, CA, USA Background: Frailty is observed at high rates among people with HIV (PWH) and occurs at younger ages compared to the general population. This higher burden of frailty is often attributed to chronic inflammation and subsequent immune exhaustion, which is increasingly being targeted as a means for mitigating frailty progression and impacts. We assessed how a panel of biomarkers of inflammation, measured in a case cohort sub-study of PWH in clinical care, is associated with frailty among PWH. Methods: A panel of 13 plasma inflammatory biomarkers was collected at a single timepoint from a subset of virally suppressed PWH in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between 2010-2018. CNICS also collects and harmonizes data on demographic information, laboratory values, diagnoses, medications, and patient reported outcomes (PROs). Frailty over time was measured with a validated phenotype of 4 components (inactivity, immobility, fatigue, and unintentional weight loss) from the PRO assessment from biomarker date through July 2022. We considered frailty scores ranging from 0-4, with one point per endorsed component. We used linear mixed models to estimate longitudinal associations between standard deviation-scaled biomarkers and frailty score, with adjustment for demographic characteristics, clinical factors and comorbidities, and coinfections. Results: Among 273 PWH, most were male (91%), average age at baseline was 45 years, 45% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 6.2 years. Several inflammatory biomarkers were associated with higher frailty scores, including those linked to microbial translocation (soluble CD14 [sCD14], lipopolysaccharide binding protein [LBP], kynurenine-to-tryptophan [KT] ratio) and systemic inflammation (C-reactive protein [CRP] and soluble tumor necrosis factor receptor 2 [sTNFR2]) (Figure 1). For example, a standard deviation higher KT ratio was associated with a 0.14-point higher frailty score (95%CI: 0.04-0.25), CRP was associated with a 0.25-point higher frailty score (95%CI: 0.16-0.34) and sCD14 was associated with a 0.20-point higher frailty score (95%CI: 0.09-0.30) over follow-up. Conclusion: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for preventing or reducing frailty in treated PWH.

837

Excess Inflammation Associated With AIDS and Non-AIDS Complications in Adults on ART Kanal Singh 1 , Shweta Sharma 2 , Birgit Grund 2 , Alejandro Arenas-Pinto 3 , Nnakelu Eriobu 4 , Edward Gardner 5 , Win Min Han 6 , Jose Hidalgo 7 , Jennifer Hoy 8 , Jakob Malin 9 , Daniel Murray 10 , Siegfried Schwarze 11 , Alan Winston 12 , Jason Baker 13 , for the INSIGHT START Study Group 1 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 2 University of Minnesota, Minneapolis, MN, USA, 3 University College London, London, United Kingdom, 4 Institute of Human Virology Nigeria, Abuja, Nigeria, 5 Denver Health Medical Center, Denver, CO, USA, 6 HIV-NAT, Bangkok, Thailand, 7 Vía Libre, Lima, Peru, 8 The Alfred Hospital, Melbourne, VIC, Australia, 9 Cologne University Hospital, Cologne, Germany, 10 Rigshospitalet, Copenhagen, Denmark, 11 European AIDS Treatment Group, Brussels, Belgium, 12 Imperial College London, London, United Kingdom, 13 Hennepin Healthcare Research Institute, Minneapolis, MN, USA Background: In START, immediate ART initiation lowered inflammation and risk for clinical events. It is unclear to what degree prolonged inflammation contributes to clinical risk after ART is initiated. We quantified the excess inflammation associated with ART deferral in START, and investigated its influence on clinical event risk during viral suppression. Methods: The START trial (2009-2021) randomized participants (pts) with CD4>500 cells/µL 1:1 to immediate or deferred (when CD4 <350 cells/µL) ART. In 2015, trial results were unblinded and all pts were advised to initiate ART. In a substudy, plasma IL-6 and D-dimer (biomarkers) levels were measured at baseline, month 8 and annually. Longitudinal averages of biomarker levels from study entry through 2015 were compared between treatment arms using rank-sum tests. Kaplan-Meier curves for time to a composite outcome (AIDS, serious non-AIDS [SNA], or death) that occurred between 2016-2021 were estimated for the upper quartile (Q4) versus the lower 3 quartiles (Q1-Q3) of average longitudinal biomarkers through 2015. Associations between average biomarker levels through 2015 and the composite were estimated using Cox models adjusted for treatment arm. Results: The analysis included 2114 pts. Through 2015 (median of 3.2 yrs), the deferred compared to the immediate arm had higher longitudinal biomarker levels: median IL-6 1.7 vs 1.5 pg/mL; D-dimer, 0.33 vs 0.27 mg/mL (both p<0.001). By 01Jan2016, 87% of pts in the deferred and 99% in the immediate arm started ART; median time to ART start in the deferred arm was 2.5 years. There were 124 AIDS, SNA, or death events from 2016-2021; 0.92 and 1.27 per 100PY in immediate and deferred arms, respectively; HR(imm/def)=0.7 (95% CI 0.5-1.0; p=0.07). Higher longitudinal IL-6 & D-dimer levels through 2015 were associated with higher risk of the composite during 2016-2021 in both arms (Figure); HR(Q4 vs Q1-Q3)=2.3(95% CI 1.6-3.2) for IL-6 and 2.1(95% CI 1.5-3.0) for D-dimer (both p<0.001), adjusting for treatment arm. Conclusion: In START, higher average levels of inflammation over several years were associated with subsequent higher risk of AIDS, SNA or death during 6 years on continuous ART. ART deferral resulted in higher levels of inflammation, which may have contributed to higher clinical event rates after pts were switched to continuous ART. Results should be interpreted with caution, but emphasize the need to diagnose HIV early to facilitate early ART initiation.

Poster Abstracts

838

Optimizing Long-Term Exercise Benefits for Older Adults With HIV: The MOVING Study Matilde Sánchez-Conde 1 , Jorge Díaz-Álvarez 1 , Rafael Garcia-Molina 2 , Jesus Fernandez-Luna 2 , Marta Martinez 2 , Brian B. Vasquez-Brolen 2 , Sara Martin Colmenarejo 1 , Pablo Ryan 2 , Fernando Dronda 1 , Fatima Branas 2 1 Hospital Ramón y Cajal, Madrid, Spain, 2 Hospital Universitario Infanta Leonor, Madrid, Spain

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