CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: There appears to be a significant role of country of residence on inflammatory and vascular biomarkers for youth with and without PHIV. The differences suggest both HIV-related factors (HIV viral clades) and non-HIV factors such as CMV status. Differences may also be due to social determinants of health, including dietary and psychosocial factors. Further studies on the lifelong consequences of HIV and environmental factors on inflammatory profiles are warranted. The figure, table, or graphic for this abstract has been removed. 1072 HIV Modifies Association of Biomarkers on Cardiac Fibrosis and Inflammation in South African Youth Jennifer Jao 1 , Lauren Bonner 1 , Shan Sun 2 , Morne Kahts 3 , Stephen Jermy 3 , Mothabisi Nyathi 3 , Nana Asafu-Agyei 3 , Justine Legbedze 2 , Emma Carkeek 3 , Grace A. McComsey 4 , Matthew J. Feinstein 1 , Irwin Kurland 5 , Landon Myer 3 , Heather Zar 3 , Ntobeko Ntusi 6 , for the CTAAC-Heart Study 1 Northwestern University, Chicago, IL, USA, 2 Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA, 3 University of Cape Town, Cape Town, South Africa, 4 Case Western Reserve University, Cleveland, OH, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 South African Medical Research Council, Cape Town, South Africa Background: Few data exist on inflammatory markers and their association with myocardial fibrosis and inflammation in youth with HIV (YHIV). Methods: The Cape Town Adolescent and Antiretroviral Cohort (CTAAC)- Heart study enrolled youth with perinatally acquired HIV (YPHIV), with non-perinatally acquired HIV (YNPHIV) and HIV-seronegative youth (HIV-) and performed cardiovascular magnetic resonance (CMR) to assess cardiac fibrosis [late gadolinium enhancement (LGE) mass and fraction, extracellular volume (ECV)] and inflammation [native T1 and T2 mapping] outcomes. Markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-a)] and immune activation [soluble (s)CD14, sCD163], cardiac injury [N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST-2] and fibrosis (galectin), and vascular activation [intercellular adhesion molecule (ICAM1)] were measured via ELISA. Quantile regression models were fit with an interaction term between HIV status and each marker to assess for effect modification by HIV status on CMR outcomes. Results: 273 YPHIV, 74 YNPHIV, and 72 HIV- were included; 56% were female. Median age and BMI were highest among YNPHIV compared to YPHIV and HIV- (20 vs. 18 and 17 years; 26 vs 22 and 22 kg/m 2 , respectively). Among YHIV, a lower proportion of YPHIV vs. YNPHIV had a CD4 >500 cells/mm 3 (57 vs. 62%) or were on integrase inhibitors (33 vs. 87%). Overall sCD14 (1934 vs. 1926 and 1759 ng/mL, p=0.002) and TNF-a (9.5 vs. 8.9 and 9.2 pg/mL, p=0.021) were highest in YPHIV vs. YNPHIV and HIV-; CRP (3001 vs. 1611 and 889 ng/mL, p=0.006) and galectin (6.7 vs. 5.5 and 5.5 ng/mL, p<0.001) were highest in YNPHIV vs. YPHIV and HIV-. HIV status significantly modified the associations of TNF-a with LGE mass (p<0.001) and native T1 (p=0.011) after adjusting for age, female sex, body surface area, prior tuberculosis, and systolic blood pressure. (Figure 1) In addition, HIV status modified the effect of IL6 on native T1 (p<0.001). There was no effect modification by HIV status on associations of all other biomarkers with CMR outcomes. Conclusions: While markers of inflammation, immune activation, and cardiac fibrosis appear to be higher in YHIV compared to HIV-, relationships of some inflammatory markers on cardiac fibrosis and inflammation are significantly different between YPHIV, YNPHIV, and HIV-. Future studies are warranted to assess markers most predictive of cardiac fibrosis and inflammation in YHIV.

52% rural vs 96% urban YPHIV had HIV-RNA <50 copies/mL, 93% of YPHIV were on TDF/3TC/DTG. OPLS-DA shows variables that could discriminate between urban and rural participants (Figure). More rural participants lived in extreme poverty, lacked access to clean water, and had lower dietary diversity compared to urban participants (p<0.001). Overall, compared to HIV-, YPHIV had lower BMI, higher waist-to-hip ratio, less dyslipidemia (p≤0.05), and higher sCD163, IFAB, IL6, hsCRP and sCD14 (p≤0.03). Urban YPHIV were more likely to have higher BMI, HOMA-IR, total cholesterol and low-density lipoprotein than rural YPHIV(p<0.001), however almost all biomarkers were higher in rural vs urban YPHIV including sCD14, sCD163, hsCRP, IL6, TNFRI, and LBP (p≤.015). After adjusting for demographic, socioeconomic, viral load and ART duration, only sCD14 remained elevated in the rural YPHIV (β-580, 95% CI -1015; -145). Conclusions: Urban and rural participants have distinct socioeconomic, metabolic, and inflammatory signatures. The separation of these factors was not directly attributed to HIV status. The monocyte activation marker sCD14, was associated with HIV status and remained elevated in rural YPHIV even after adjusting for differences in HIV factors. Increasing the inclusion of rural populations in SSA is paramount as we focus on preventing cardiometabolic comorbidities in aging YPHIV.

Poster Abstracts

1071 US and Ugandan HIV Youth: Exploring Differences in Inflammatory, Chemokine, and Vascular Signatures Sahera Dirajlal-Fargo 1 , Shan Sun 2 , Jacqueline D. Corry 3 , Kate Ailstock 3 , Nate Lucas 3 , Morgan Cummings 3 , Rashidah Nazzinda 4 , Christine Karungi 4 , Victor Musiime 4 , Danielle Labbato 5 , Brian Reinert 3 , Namal Liyanage 3 , Jesse Kwiek 3 , Grace A. McComsey 6 , Nicholas Funderburg 3 1 Northwestern University, Chicago, IL, USA, 2 Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA, 3 The Ohio State University, Columbus, OH, USA, 4 Joint Clinical Research Centre, Kampala, Uganda, 5 University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 6 Case Western Reserve University, Cleveland, OH, USA Background: Persistent antigen exposure may alter the development of the immune system in early life and inflammatory profiles may vary by geographic location and ethnicity. We have previously highlighted evidence of ongoing immune activation in youths with perinatally acquired HIV (YPHIV). We analyzed differences in inflammatory, chemokine and vascular biomarkers among YPHIV and seronegative (HIV-) youths in US and Uganda. Methods: We measured plasma inflammatory biomarker levels in YPHIV and HIV- youths in the US (76) and Uganda (98) by ELISA and by the proinflammatory chemokine and vascular inflammation Legendplex panels. Biomarkers were compared using Wilcoxon rank-sum tests. Volcano plots were used to visualize differences in log-transformed fold changes (FC) of medians and their corresponding p-values between the two countries within each HIV status group. Results: US participants were slightly younger (median age 14 yrs) than Ugandan participants (16 yrs) but were similar by sex (52% female). For YPHIV, median ART duration was 13.5 years, 100% of Ugandan and 87.5% of US YPHIV had HIV-1 RNA<50 c/mL. CMV antibodies were detected in 85% of Ugandans, and in 53% of US youth. Comparing markers by HIV status, we found that in Uganda, only d-dimer, and the chemokines CCL20 and CCL5 were higher in YPHIV compared to HIV-; in the US, however, several chemokines and inflammatory, gut, and vascular markers were higher in YPHIV compared to HIV-. We compared markers by site and found that levels of monocyte activation (sCD14) and vascular inflammation (ICAM, matrix metalloproteinase-9, osteopontin, serum amyloid A) were higher in US compared to Ugandan YPHIV; while markers of coagulation, lipid oxidation, systemic inflammation (d-dimer, IL6, OX LDL, TNFR II) and several chemokines (ENA-78, GROa, MIO_1a and MIP3a) all chemoattractant for neutrophils, monocytes and macrophages, were higher in Ugandan compared to US YPHIV. Several markers in each class were higher in Ugandan compared to US HIV- (see Figure).

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