CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

considered as risk-combination-index. Cox models were developed to evaluate the effect of risk-combination-index in the prediction of MACE. Results: We studied 370 subjects with a median follow-up time of 175 (131 191) months. Main baseline characteristics are shown in table 1. HCV-ab were positive in 25.9% of subjects, all of them were treated and had undetectable HCV RNA during follow-up. A total of 19 MACE (8 myocardial infarction, 6 stroke, 5 peripheral arterial disease) were registered. Along follow-up 39% developed metabolic syndrome, 37% hypertension and 17.6% DM2. TyG>4.68 was found in 56% of subjects and FiB-4>1.3/1.45 in 29.5%, these proportions being significantly higher in PLWH with MACE (74% and 55% respectively). The proportion of subjects with a risk-combination-index was 42% in MACE population vs 14% in non-MACE-population (p<0.05). Cox regression model adjusted by age, HIV infection duration and HCV coinfection showed that risk combination-index was associated with MACE: HR 2.6 (CI95% 1.02-6.6; p=0.04). Conclusion: The combined interpretation of TyG and FIB-4 indexes, as surrogate markers of insulin resistance and a proxy of liver fibrosis might have a potential predictive value of major cardiovascular events in PLHIV. We recommend routine use of these indexes in the care of PLVIH with metabolic disorders. T-Cell Subsets and Incidence of Diabetes in Persons With HIV in the ACTG Study A5001 Katherine Tassiopoulos 1 , Kunling Wu 1 , Robert C. Kalayjian 2 , Susan L. Koletar 3 , Frank Palella 4 , John Koethe 5 , Alan Landay 6 1 Harvard TH Chan School of Public Health, Boston, MA, USA, 2 MetroHealth Medical Center, Cleveland, OH, USA, 3 The Ohio State University, Columbus, OH, USA, 4 Northwestern University, Chicago, IL, USA, 5 Vanderbilt University, Nashville, TN, USA, 6 Rush University, Chicago, IL, USA Background: Persons with HIV (PWH) have persistent changes in T cell subsets that can also be modified by aging, and may contribute to the high burden of comorbid conditions, including type 2 diabetes (DM), in older PWH. While studies in persons without HIV have found few associations between T cell subsets and DM or pre-DM, a recent study of US veterans with HIV found higher frequencies of effector memory and senescent CD4+ T cells associated with incident DM. Here, we examined associations of T cell subsets measured at a uniform time post-ART initiation with incident DM among PWH in the AIDS Clinical Trials Group study A5001. Methods: DM was defined as: 2 consecutive non-fasting glucose >200 mg/dl or fasting glucose >126 mg/dl; DM diagnosis; or oral antiglycemic or insulin use for >30 days. We used Cox proportional hazards models to evaluate associations of T cell subsets measured 1 yr post-ART with incident DM. PWH with prevalent DM (≤ 1yr post-ART) were excluded. Multivariable models included age at ART start, sex at birth (gender not available), self-reported race/ethnicity, smoking status, time-updated BMI, triglycerides, and history of hypertension. We explored effect modification by demographic and clinical factors by including interaction terms between each T cell subset and effect modifier in multivariable models. Results: 1015 PWH had ≥1 subset (% activated CD4 or CD8 [HLA-DR+/CD38+], % senescent CD4 or CD8 [CD28-], % memory CD4 [CD45RA-/CD45RO+], % naïve CD4 [CD45RA+/CD62L+]) measured 1yr post-ART. Most (82%) participants were male; 48% White non-Hispanic, 31% Black non-Hispanic, and 21% Hispanic/ other ethnicity. Median age was 36 years (Q1,Q3=31,43). There were 62 DM events. PWH with DM were older, had higher triglycerides, higher BMI, and were more likely to have hypertension or low CD4/CD8 ratio than those without DM. PWH in the lowest quartile of % naive CD4 cells had a higher incidence of DM than those in higher quartiles (Figure). The association for lowest vs higher quartiles (combined) was observed in PWH <45 years (aHR=2.08 95% CI=1.00,4.34) but not ≥45 years (aHR=1.17, 95% CI= 0.44,3.11), though the interaction by age was not significant (p=0.32). There were no associations with other T cell subsets and DM. Conclusion: A lower proportion of naïve CD4+ T cells, potentially reflective of reduced naïve cell replenishment or increased memory cell inflation, may be associated with increased diabetes incidence in PWH, particularly among younger persons.

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Subcutaneous Adipose Tissue Myofibroblasts Are Associated With the Lipidome Samuel Bailin , Curtis L. Gabriel, Run Fan, Fei Ye, Mona Mashayekhi, Rama D. Gangula, LaToya Hannah, Jonathan A. Kropski, Spyros Kalams, Simon A. Mallal, Celestine Wanjalla, John Koethe Vanderbilt University Medical Center, Nashville, Tennessee Background: Dyslipidemia is common in persons with HIV (PWH) and mechanistically linked to the development of metabolic disease. Higher plasma triacylglycerides (TG) are associated with the diabetes, while an inverse relationship is observed for sphingomyelin (SM) and phosphatidylcholine (PC) species. Adipose tissue has a critical role in regulating lipid homeostasis, but how adipose tissue cellular composition might influence circulating lipid classes in PWH is unknown. We hypothesized that greater pro-inflammatory macrophage and pro-fibrotic stromal cells in subcutaneous adipose tissue (SAT) are associated with higher circulating TG and lower SM and PC species. Methods: We performed single-cell RNA sequencing on SAT biopsies from PWH on contemporary antiretroviral therapy with virologic suppression and a range of metabolic fitness. We characterized SAT cell types except adipocytes, which are poorly captured with this method. We simultaneously performed untargeted lipidomic liquid chromatography-high resolution tandem mass spectrometry on plasma samples. We assessed the relationship of cell composition with normalized summed-lipid class intensities with partial Spearman's adjusted for statin use, sex, body mass index (BMI) and diabetes status. Results: A total of 55 participants were included in this study (non-diabetic=19, prediabetic=18, diabetic=18). The median age was 49 years, BMI 31.5 kg/m 2 , 73% male, 49% White, and 62% treated with an integrase strand transfer inhibitor-based regimen. A higher proportion of myofibroblasts (pro-fibrotic cells) was positively associated with TG (ρ=0.41, p=0.006) and oxidized TG (OxTG; ρ=0.39, p=0.002) levels, and inversely associated with SM (ρ=-0.27, p=0.03) and plasmenyl phosphatidylethanolamines (plasmenyl-PE) (ρ=-0.44, p=0.004) but not PC (ρ=-0.22, p=0.11) (Figure 1). Higher intermediate macrophages (IMs) were inversely associated with plasmenyl-PE (ρ=-0.36, p=0.04). The proportion of lipid-associated macrophages (LAMs) was not associated with any lipid class. Conclusion: In PWH, higher proportion of SAT myofibroblasts was moderately associated with higher TG and OxTG, and inversely related to SM and plasmenyl PE. IMs and LAMs were not significantly associated with these classes except IMs and plasmenyl-PE. These results suggest that a pro-fibrotic composition of non-adipocyte stromal cell types is related to circulating lipid profiles. Future studies using single nuclei RNA-sequencing will be necessary to evaluate the contribution of adipocyte populations.

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Poster Abstracts

CROI 2024 242