CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

index score (1/3log(IL-6)+2/3 log(TNFR1)). Multivariable logistic regression and Poisson regression were used to examine associations among inflammatory markers and prevalence and incidence of frailty, CI, clinical events and all-cause mortality. Lastly, we used 10-fold cross validation to examine whether addition of inflammatory markers to frailty improve ability to predict incident clinical events. Results: Among 484 participants included (17% assigned female at birth, 25% Black and 20% Hispanic), median age was 56 years. Median BMI was 27 kg/m 2 , median CD4 and nadir CD4 were 627 and 189 cells/µL, and 95% had HIV RNA <200 copies/mL. 8% (38/484), 32% (144/453) and 43% (210/484) participants had frailty, CI and major clinical events at baseline. IL-6, TNFR1, CXCL-9 and inflammatory index score were associated with increased risk of prevalent frailty and clinical events, but not CI, at baseline ( Figure ). Incident rates (95%CI) of frailty, CI and clinical events were 3.72 (2.93-4.64), 9.58 (7.93-11.49) and 6.28 (5.02-7.75) per 100 person-years, respectively. CXCL-9 (Q4 vs. Q1) and TNFR1 were associated with an increased risk of incidence of both frailty and clinical events; inflammatory index was associated with only clinical events in the quartile analysis (Q4 vs. Q1), and higher inflammatory markers included (except CXCL-9) were also associated with an increased risk of all-cause mortality. The addition of TNFR1 or inflammatory index to baseline frailty increased the predictability of incident clinical events and mortality. Conclusions: Increased inflammation was associated with increased risk of prevalent and incident frailty and major clinical events/all-cause mortality, but not CI. Inflammatory markers and frailty together may better predict clinical events and mortality. The figure, table, or graphic for this abstract has been removed. Novel Biomarkers Link Inflammation, T-Cell Exhaustion, Bone Health, and Frailty in People With HIV Michael L. Freeman 1 , Wendy Fitzgerald 2 , Brian Clagett 1 , Leonid Margolis 3 , Kristine M. Erlandson 4 , Carey Shive 5 1 Case Western Reserve University, Cleveland, OH, USA, 2 National Institute of Child Health and Human Development, Bethesda, MD, USA, 3 Ilia State University, Tbilisi, Georgia, 4 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 5 VA Northeast Ohio Healthcare System, Cleveland, OH, USA Background: Chronic inflammation is a critical driver of morbidities and mortality in normal aging. In people with HIV (PWH), inflammation can lead to increased incidence and earlier onset of non-AIDS comorbidities and aging syndromes, such as frailty. Here, we measured plasma markers of inflammation and T cell phenotypes from PWH with and without frailty to investigate immunologic parameters associated with frailty in PWH. Methods: Inflammatory markers in blood plasma and T cell phenotypes in peripheral blood mononuclear cells (PBMCs) from PWH without frailty (0 Fried score, n=60, 20% female, median age 58 years) and with frailty (≥3 Fried score, n=60, 30% female, median age 59.5 years) were measured by Luminex assay or flow cytometry, respectively. All participants were enrolled in the longitudinal observational HAILO study performed by the ACTG (A5322). Multiple least squares linear regression analysis was used to determine the association of each marker with frailty when adjusting for age, sex at birth, and race. Spearman correlations were used to determine the association of plasma markers with CD4 T cell phenotypes. Results: We found that 19 (25.3%) of 75 markers measured in plasma were significantly associated with frailty in adjusted analyses (Figure), most of which are downstream of NF-kB signaling and include IL-6, IL-15, IFNg, and the chemokines IL-8, CCL3, CCL11, and CCL19. In adjusted analyses, the proportion of CD4 T cells with a naïve phenotype was significantly reduced in frail individuals and the proportion of CD4 T cells expressing the activation/exhaustion marker PD-1 was significantly elevated in frail individuals. Of the 19 markers associated with frailty, we found that only osteoprotegerin was significantly correlated with both percent naïve (rho=-0.266, P =0.042) and percent PD-1+ (rho=0.409, P =0.001) CD4 T cells among PWH with frailty. Conclusions: We found a strong association of NF-kB related inflammation with frailty in PWH. Osteoprotegerin, which may be elevated in PWH and has been linked to frailty in people without HIV, is a TNF-receptor superfamily member that acts as a soluble decoy receptor for receptor activator of NF-kB ligand (RANKL) to inhibit osteoclast formation and prevent bone resorption via the RANKL/RANK pathway. Low proportion of naïve CD4 T cells and increased PD-1 expression was associated with both osteoprotegerin levels and frailty in

PWH, suggesting a link between inflammation, T cell activation, bone health, and frailty in PWH.

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The Association of Cytomegalovirus Serostatus on Immune Recovery Among People With HIV Raynell Lang 1 , Joshua Quisias 2 , Sally B. Coburn 3 , Hartmut Krentz 1 , Brenda Beckthold 4 , Kevin Fonseca 1 , Michael Parkins 1 , M. John Gill 1 1 University of Calgary, Calgary, Canada, 2 University of British Columbia, Vancouver, Canada, 3 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 Southern Alberta Clinic, Calgary, Canada Background: Cytomegalovirus (CMV) infection is common among people with HIV (PWH) and may contribute to immune activation and inflammation, which could hinder immune recovery with antiretroviral therapy (ART). Within the Southern Alberta HIV Clinic (SAC) in Calgary Canada, we aimed to identify the seroprevalence of CMV and its association with CD4 T-cell and CD4/CD8 ratio recovery among PWH who maintain HIV viral suppression. Methods: PWH 18 years or older accessing care at SAC between 01/01/1998 01/06/2022 with at least one CMV serologic test and initiated on ART were included at the first HIV viral load result of <200 copies/mL (study entry). Study exit was defined as the first date the patient reached the study outcome [CD4 cell count of >499 cells/mm 3 (model 1) or CD4/CD8 ratio >1 (model 2)], had a viral load measurement of >200 copies/mL (as a proxy for ART adherence), lost-to follow up, death, or 01/06/2022. PWH were excluded if they had <2 measurements for CD4 or CD4/CD8 ratio during the study period. Continuous time-to-event Cox proportional hazard models estimated crude and adjusted hazards ratios (aHR) and 95% confidence intervals for CD4 count recovery to >499 cells/mm 3 and CD4/CD8 ratio of >1 at 10 years by CMV serostatus. Models were adjusted for calendar year, age, sex, race/ethnicity, HIV acquisition risk, HCV, HBV, renal disease, diabetes, cardiovascular disease, and CD4 nadir. 10-year cumulative incidence of CD4 and CD4/CD8 ratio recovery by CMV serostatus was estimated using Kaplan-Meier methods. Results: Among 2,538 PWH, 2,310 (91%) were CMV seropositive, 787 (31%) had initial CD4 counts of >499 cells/mm 3 and 369 (15%) had initial CD4/CD8 ratios >1 and were excluded from the analyses. Over 10 years, 84% of CMV seropositive and 85% of CMV seronegative PWH achieved a CD4 count of >499 cells/mm 3 and 53% of CMV seropositive and 72% of CMV seronegative PWH achieved a CD4/CD8 ratio of >1 ( figure ). CMV seronegativity was not associated with CD4 recovery to 500 cells/mm 3 (aHR 1.08 [0.84-1.40]), however, was associated with a greater likelihood of a CD4/CD8 ratio of >1 (aHR 2.32 [1.80 3.00]) at 10-years of follow-up. Conclusions: CMV coinfection is common among PWH. CMV is associated with a reduced CD4/CD8 ratio recovery, however, not with CD4 T-cell recovery among PWH who maintain HIV viral suppression. This suggests CMV may contribute to chronic infection-mediated immune activation and inflammation among PWH.

Poster Abstracts

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