CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

767

Changes in Gut Microbiota Associated With Progression of Atherosclerosis in People With HIV

Javier García-Abellán 1 , Marta Fernández-González 1 , Vanesa Agulló 1 , José Alberto García 1 , Sergio Padilla 1 , Catalina Robledano 1 , Ronald Galdamez 1 , Leandro López 1 , Paula Mascarell 1 , Angela Botella 1 , Nuria Ena 1 , Lidia García 1 , María José Gosalbez 2 , Félix Gutiérrez 1 , Mar Masiá 1 1 Hospital General Universitario de Elche, Elche, Spain, 2 FISABIO, Valencia, Spain Background: Variations in gut microbiome might modulate host immune activation and inflammation, potentially linked to increased cardiovascular risk. Our objective was to longitudinally characterize the distinctive features of gut microbiota associated with progression of atherosclerosis measured through carotid artery intima-media thickness (cIMT) in people living with HIV (PLWH). Methods: 96-week, longitudinal study in virologically suppressed (HIV-1 RNA <50 copies/mL) PLWH with no previous cardiovascular disease. cIMT was measured at baseline, 48 and 96-weeks visits using B-mode ultrasound at 6 locations. cIMT progression was defined as an increase >10% and/or detection of new carotid plaques. To profile the gut microbiome, DNA was extracted from fecal samples and quantified with the Qubit dsDNA HS Assay Kit. Amplification and sequencing of 16S ribosomal RNA (V3-V4 variable regions) were carried out following the Illumina protocol. For bioinformatic analysis of amplicons, the QIIME package was used. Biomarker analysis was performed using the LEfSe software package. Results: 202, 190 and 169 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. At the 96w visit, 87 (43%) patients were categorized as progressors, with 54 (26.7%) of them showing a new carotid plaque. No significant differences were observed in α-diversity indices between groups at baseline. Over the 96w follow-up period, a decrease in α-diversity (Simpson's and Shannon's indices) was observed in the progressor group. Based on beta-diversity analysis at the species level, determined through principal coordinate analysis (PCoA) distances, the progressor and non-progressor groups exhibited distinct and divergent microbial profiles during each follow-up visit (p=0.001). When all sequences from the three visits were compared, the PCoA plots of Bray-Curtis distance revealed that the samples clustered in accordance with the progression of atherosclerosis (p=0.016; Permanova test) (Fig1A). LEfSe analysis revealed distinct associations between progression and specific bacterial taxa (Fig1B). Agathobacter , Ruminococcus_2 and Lachnospiraceae_UCG_003 genus were consistently observed in various consecutive visits as distinctive genus associated with progression, while Prevotella_7 and Allisonella genus were linked to non-progressor patients. Conclusion: Progression of atherosclerosis in PLWH is associated with distinctive changes in the gut microbiota.

766

Association Between HIV Infection and Survival for Head and Neck Cancers in the US From 2008-2020 Devesh S Malgave 1 , Ado S. Rivera 2 , Christine Hartman 3 , Jennifer R. Kramer 3 , Peter Richardson 3 , Efthalia Zafeiropoulou 3 , Rulin Hechter 2 , Matthew Boyer 4 , Dong Yongquan 3 , Lori Sakoda 5 , Donna White 3 , Wendy Leyden 5 , Michael J. Silverberg 5 , Elizabeth Y. Chiao 6 1 University of Texas at Houston, Houston, TX, USA, 2 Kaiser Permanente Southern California, Pasadena, CA, USA, 3 Baylor College of Medicine, Houston, TX, USA, 4 Duke University School of Medicine, Durham, NC, USA, 5 Kaiser Permanente Northern California, Oakland, CA, USA, 6 University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: People with HIV (PWH) are at an increased risk of head and neck cancer (HNC) compared with people without HIV (PWoH). However, little is known regarding the impact of HIV on HNC survival. This study is one of the first to compare survival, by histological subtype of HNC, between PWH and PWoH. Methods: A retrospective cohort of adults with newly diagnosed 1) oropharyngeal, 2)non-oropharyngeal (hypopharynx and larynx), 3)oral cavity cancers was identified using electronic health record data from the National Veterans Administration and Kaiser Permanente California regions from 2008 to 2020. Separate Cox regression models were used to assess the association of HIV infection with overall survival (OS) for each cancer type, adjusting for baseline sociodemographic factors, clinical characteristics, and HPV+ tumor status (oropharyngeal only). Multiple imputation was used for missing covariate data. Results: Our analysis included 300 PWH and 30,950 PWoH HNC patients. Compared with PWoH, PWH were more likely to be younger; male; Black or Hispanic; had lower education attainment and income levels; and have co-infection with HPV, HBC, or HCV. Mortality rates for PWH vs. PWoH were 13.0 vs.9.7 per 100 person-years for oropharyngeal; 7.3 vs.13.0 for oral cavity; and 12.0 vs.14.0 for non-oropharyngeal cancers. In unadjusted analysis, HIV infection was associated with worse OS for oropharyngeal cancer (hazard ratio [HR]:1.31, 95%CI:1.02-1.66); better OS for oral cavity cancer (HR:0.57, 95%CI:0.39-0.82); and similar OS for non-oropharyngeal cancers (HR:0.83,95%CI:0.63-1.10). In adjusted analysis, similar trends were observed with worse OS in oropharyngeal cancer patients (HR:1.38, 95%CI:1.08-1.77); better OS in oral cavity cancer (HR: 0.66, 95%CI:0.46-0.96); and similar OS for non-oropharyngeal cancer (HR:0.94, 95%CI: 0.71-1.25). However, for oropharyngeal cancers, patients with HPV+ tumors had better survival compared with patients with HPV-negative tumors (HR: 0.50, 95%CI: 0.47 0.53). Other risk factors for poor OS for HNCs included older age at cancer diagnosis, early year of cancer diagnosis, higher stage of cancer, higher Charlson comorbidity index, alcohol abuse diagnosis, and ever smoking. Conclusion: The study results suggest that PWH had poor survival for oropharyngeal cancer but better survival for oral cavity cancers compared with PWoH. Further research should focus on finding the etiological factors influencing HIV's role in outcomes related to HNCs.

Poster Abstracts

768

Plasma IL-1β Predicts Incident Coronary Artery Disease and Pulmonary Embolism in PWH on ART Sannidhi Sarvadhavabhatla 1 , Lei Shi 2 , Junzhe Shao 2 , Maria Sophia B. Donaire 1 , Vivian Pae 1 , Alton Barbehenn 1 , Danny Li 1 , Xiuping Chu 3 , Colin T. Maguire 4 , Priscilla Y. Hsue 1 , Jingshen Wang 2 , Rafick P. Sekaly 5 , Brian K. Agan 3 , Jeffrey A. Tomalka 5 , Sulggi A. Lee 1 1 University of California San Francisco, San Francisco, CA, USA, 2 University of California Berkeley, Berkeley, CA, USA, 3 Infectious Disease Clinical Research Program, Bethesda, MD, USA, 4 University of Utah, Salt Lake City, UT, USA, 5 Emory University, Atlanta, GA, USA Background: Despite antiretroviral therapy (ART), people with HIV (PWH) experience higher rates of morbidity and mortality vs. age-matched HIV negative controls which may be driven by chronic inflammation due to persistent virus. Plasma interleukin 6 (IL-6) levels are amongst the strongest predictors of mortality in PWH on ART, and an upstream regulator of IL-6, interleukin-1 beta (IL-1β), may be the major driver of this risk. Methods: We performed a case-cohort study of 1,002 PWH on ART from the U.S. Military HIV Natural History Study. Inclusion criteria were HIV-1 infection

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