CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Compared to NC, those with prior COVID-19 had an altered metabolic and inflammatory profile at 4 months post-COVID, mostly irrespective of LC symptoms. Post-COVID, we observed sustained caspase-1/4/5 activity (NC:0.95 vs COVID:1.05, p=0.0026, expressed as median of the fold change) and mitochondrial superoxide production (NC:0.9 vs COVID:1.24, p=0.005) in monocytes, indicative of inflammasome activation and oxidative stress, respectively, along with an enrichment in HLA-DR lo /p16 INK4alo immature monocytes. This was accompanied by elevated inflammatory plasma biomarkers, including lipid mediators such as high arachidonic acid (NC:138 µg/ mL vs COVID:268.5, p<0.0001), decreased tryptophan levels (NC:11.85 µg/mL vs COVID:9.34, p<0.0001), and alterations in the frequency of peripheral immune cell subsets. In comparison to RC participants, we identified a distinct subset of senescent effector CD8 T-cells in those who developed LC, characterized by lower expression of CD57 (RC:2311 vs LC:1344, p<0.004), an indicator of cytotoxic capacity, and higher levels of p16 INK4a , a cellular senescence marker (p<0.03). Finally, a principal component analysis with the most differentiating markers demonstrated unique immunometabolic profiles in NC vs COVID groups (Figure 1A), while differences between RC and LC groups were more subtle (Figure 1B). Conclusions: SARS-CoV-2 infection can have a profound and sustained immunometabolic effect, which could contribute to post-acute morbidity. A combination of disjointed innate and adaptive immune recovery with metabolic alterations may contribute to LC. Our data suggest an ongoing perturbation of immunometabolic homeostasis for months following COVID-19, and could guide evaluation of treatments focused on modulating immune or metabolic pathways involved in persistent LC symptoms. Immune & Virologic Trajectories 1.5 Years Before and After COVID-19 in an Early-Treated HIV Cohort Ferron F. Ocampo 1 , Tyler Hamby 2 , Luxe-Naree Poonpitak 3 , Carlo Sacdalan 3 , Suwanna Puttamaswin 3 , Somchai Sriplienchan 3 , Nittaya Phanuphak 4 , Phillip Chan 5 , Trevor Crowell 2 , Lydie Trautmann 6 , Sandhya Vasan 6 , Robert Paul 7 , Serena Spudich 5 , for the RV254/SEARCH 010 Study Team 1 University of Toronto, Toronto, Canada, 2 US Military HIV Research Program, Bethesda, MD, USA, 3 SEARCH, Bangkok, Thailand, 4 Institute of HIV Research and Innovation, Bangkok, Thailand, 5 Yale University, New Haven, CT, USA, 6 Henry M Jackson Foundation, Bethesda, MD, USA, 7 University of Missouri St Louis, St Louis, MO, USA Background: SARS-CoV-2 infection can be associated with immunologic dysfunction and might serve as a ‘second hit’ to immune function in people with HIV (PWH) despite suppression with antiretroviral therapy (ART). We leveraged the RV254 Thai cohort to examine the trajectory of immunologic and virologic parameters 1.5 years pre- and post-COVID-19 in PWH on stable ART initiated during acute HIV infection (AHI). Methods: RV254 participants are enrolled during AHI (Fiebig I-V), initiated ART within days, and undergo serial longitudinal blood (CD4+ & CD8+ T-cell counts, HIV RNA) tests. In participants on ≥ 48 weeks of stable ART with documented COVID-19, immunologic measures 1.5 years pre- to post-COVID-19 were regressed on time using linear mixed models. Time in years since COVID-19 diagnosis was entered as a linear spline with knots at the time of COVID-19 diagnosis and 0.25-year intervals thereafter; each time point after diagnosis was compared with the value at the time of diagnosis. Rates of detectable viral load (> 50 copies/ml) before and after COVID-19 diagnosis were compared using Poisson regression generalized estimating equations. Results: Between 4/2021 and 9/2022, 262 participants on ≥48 weeks of stable ART (97% males, median age 32 [interquartile range 29-38]) were diagnosed with COVID-19. Of these, 213 (82.1%) were diagnosed during the Omicron wave; 224 (85.5%) received ≥2 doses of COVID-19 vaccines prior to diagnosis; 4 (1.5%) required supplemental oxygen; 1 (0.4%) required intensive care and there were no fatalities. Compared with values at the time of COVID-19 diagnosis, there were significant declines in estimated CD4+ T-cell count (from 710.77) at 6 (679.62, p =0.030) and 9 (668.14, p =0.008) months and the CD4+/CD8+ T-cell ratio (from 1.13) at 3 (1.09, p =0.019), 9 (1.07, p <0.001), and 12 (1.08, p =0.006) months after diagnosis ( Figure 1 ). CD8+ T-cell count was stable over this period. Estimated rates of detectable viral load per year decreased post-COVID (5.6% vs. 2.2%, p =0.04). Conclusions: In this cohort of young, mostly male PWH with viral suppression after early ART, we observed mild but significant changes in the trajectory of The figure, table, or graphic for this abstract has been removed.

CD4+ T-cell count and CD4/CD8 ratio up to one year after COVID-19. Detectable viral load rates decreased post-COVID-19 but CD8+ T-cell count remained stable. Longer follow-up and additional studies to disentangle the effects of COVID-19 vaccination and reinfections are ongoing to determine the impact of COVID-19 on the immunologic and virologic outcomes in PWH.

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Longitudinal Changes in Arterial Stiffness and Inflammation From Pre- to Post-COVID-19 Infection Jhony Baissary 1 , Ornina Atieh 1 , Jared C. Durieux 2 , Alexander Merheb 3 , Danielle Labbato 2 , Theresa Foster 2 , Michael Rodgers 2 , Grace A. McComsey 1 1 Case Western Reserve University, Cleveland, OH, USA, 2 University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 3 Harvard University, Cambridge, MA, USA Background: We have previously shown in cross-sectional studies that COVID-19 infection was associated with arterial stiffness and increased oxidized LDL (oxLDL). In this study, we assess changes in these cardiovascular parameters after COVID infection in a group of individuals who have documented pre-COVID assessments. Having pre-COVID assessments has been a limitation of current studies. Methods: This prospective cohort study used FDA-approved EndoPAT2000 to measure the Augmentation Index (AI; arterial stiffness) and Reactive Hyperemic Index (RHI; endothelial function) in a group of individuals with available pre pandemic measurements and a documented COVID-19 infection. A detailed medical and COVID-19 history were collected, and inflammatory and metabolic markers were measured. Linear mixed models with random intercept were used to estimate the effects of COVID-19 infection on markers of endothelial function, inflammation, gut permeability, and monocyte activation. Results: Among the 78 participants (53% non-white race, 40% female), median age was 47 years and BMI 28 kg/m 2 . The median duration between pre-pandemic and post-COVID infection was 3 years, and between COVID infection and post-COVID assessment 451 days. At the pre-pandemic visit, 34% of participants had RHI ≤1.67 and the median AI was 2.0. At follow-up, the proportion of participants with abnormal RHI did not change, but the proportion of participants with elevated arterial stiffness (AI≥2.0) increased by 15.3% (P<.0001), and significant increases in ICAM (P=0.02), sCD14 (P=0.01), sCD163 (p=0.001), and OxLDL (P= 0.03) were observed. Non-HDL cholesterol improved, without change in HbA1C or weight. After adjustment, female sex had more than six times [aOR: 6.2 (95% CIs: 1.5, 25.7); P=0.01] higher likelihood of having higher AI compared to male sex. Changes in arterial stiffness were not correlated with metabolic (weight, hbA1c, lipids) or inflammatory markers. Conclusions: COVID infection is associated with arterial stiffness; female sex seems mostly affected. Long term cardiovascular effects of arterial stiffness are very concerning in this population and should be investigated. [18F]F-AraG PET Imaging Reveals Increased Gut T-Cell Activation in People With Long COVID Timothy J. Henrich 1 , Michael Peluso 1 , Robert Flavell 1 , Dylan Ryder 1 , Kofi Asare 1 , Emily Fehrman 1 , Thomas Dalhuisen 1 , Rebecca Hoh 1 , Badri Viswanathan 1 , Youngho Seo 1 , Jelena Levi 2 , Jeffrey Martin 1 , Steven G. Deeks 1 , Henry VanBrocklin 1 , Emilio De Narvaez 1 , for the UCSF LIINC Study Team 1 University of California San Francisco, San Francisco, CA, USA, 2 CellSight Technologies, Inc, San Francisco, CA, USA Background: We previously demonstrated increased T cell activation across many tissue types in people months to years following SARS-CoV-2 infection

Poster Abstracts

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CROI 2025 292