CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1073 Changes in Inflammatory Biomarkers Among Youth Living With Perinatal HIV Infection and Exposure

adolescence, it is important to identify who is at the highest risk of premature cardiovascular disease. We hypothesized that these children can be stratified into inflammatory phenotypes, enabling the identification of those requiring more intensive monitoring. Methods: Participants included 133 children aged 7–13 years, previously part of the CHER and P1060 trials and followed at Tygerberg Hospital, South Africa. 66 children initiated ART <3 months old; 10 between 3 and 6 months, and 57 initiated ART >6 months old. Children were seen 3-monthly for clinical care and had largely sustained viral suppression, preserved CD4+ cell count and minimal clinical HIV disease. We measured 26 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. We conducted unsupervised exploratory analysis consisting of principal components analysis followed by k-means clustering to develop inflammation phenotypes, after adjusting biomarkers for height (as a surrogate for age, puberty onset and growth), gender and ethnicity using a multivariate multiple linear regression model. Results: Two distinct phenotypes were identified – a high and low inflammation phenotype. High inflammation was characterized by high levels of both myeloid (IL-18, IL-6, TNF-α, MCP1, IL-1α, S100A9, IL-1ra and S100A8) and lymphoid (IL-17, IFNγ, IL-12p70, IL-10) biomarkers of inflammation. This was accompanied by elevated markers associated with premature cardiovascular disease (elevated levels of VEGF, E-selectin, P-selectin, sCD163, VCAM1 and ICAM1). Children living with HIV in the high inflammation phenotype tended to start ART later (p = 0.053) and have a lower BMI z-score (p = 0.08) than those in the low inflammation subgroup. No differences in exposure to tobacco smoke, viral load or CD4 count was found between groups. Conclusions: A high-risk phenotype has been identified who will require more intensive surveillance and targeted follow-up for premature cardiovascular disease.

Russell B. Van Dyke 1 , George W. Sawyer 2 , Paige Williams 2 , Wendy Yu 2 , Armando J. Mendez 3 , Engi F. Attia 4 , Mariana Gerschenson 5 , Steven E. Lipshultz 6 , for the Cardiac Toxicity Sub-Study of the Pediatric HIV/AIDS Cohort Study 1 Tulane University, Metairie, LA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of Miami Miller, Miami, FL, USA, 4 University of Washington, Seattle, WA, USA, 5 University of Hawaii, Honolulu, HI, USA, 6 University at Buffalo, Buffalo, NY, USA Background: HIV infection is associated with systemic immune activation. We longitudinally evaluated levels of circulation inflammatory biomarkers in youth with perinatal HIV (PHIV) and those perinatally HIV-exposed but uninfected (PHEU). Methods: In a longitudinal sub-study of cardiac status among youth in the Pediatric HIV/AIDS Cohort Study, we measured 8 inflammatory biomarkers (Interleukin [IL]-1b, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-a [TNF-a], soluble TNF receptor 2 [sTNF-R2], and high-sensitive C-reactive protein [hsCRP]) at the start of the sub-study (T1) and ~11 years later (T2) among 99 PHIV and 59 PHEU participants with paired samples. At T1, the median age for PHIV was 13.0 years (64% female) and for PHEU, 11.2 years (56% female). Among PHIV, univariate and multivariate linear regression models were used to evaluate the associations of inflammatory biomarker levels at T2 with specific combination antiretroviral (cART) regimens, CD4 count, and viral load (VL). Results: Among PHIV: 93% were receiving cART at T1 and 92% at T2; 72% had a viral load (VL) <400 copies/mL at T1 and 81% at T2; and 81% had a CD4 cell count > 500 cells/mm 3 at T1 and 64% at T2. At T1, median levels were significantly higher among PHIV than PHEU for interleukin-18 (258 pg/mL, vs. 216 pg/mL, respectively) and TNF-a (8.3 pg/mL vs. 6.0 pg/mL). Among both groups, median levels of most biomarkers decreased between T1 and T2 except for TNF-a (increased in the PHEU group) and hsCRP (increased in both groups, see figure) There was a significantly greater decrease among PHIV than PHEU for IL-6, IL-8, IL-10, and TNF-a. At T2, only median TNF-a levels were significantly higher among PHIV than PHEU (1,880 pg/mL vs. 1,600 pg/mL). At T2: participants with a nadir CD4 <15% had 31% lower IL-8 levels (95% CI -60% to +17%) than those with nadir CD4%>25%; a CD4 count ≤500 was associated with 52% higher IL-18 levels (95% CI 11% to 110%); a VL ≥400 was associated with 91% higher sTNF-R2 levels (95% CI 22% to 200%); and integrase inhibitor use was associated with a 5%/year increase in IL-10 levels (95% CI 0.03% to 9.6%). Conclusions: PHIV participants receiving cART and PHEU initially had similar levels of inflammatory biomarkers and most decreased over ~11 years in both groups. There was a significantly greater decrease among PHIV than PHEU for IL-6, IL-8, IL-10, and TNF-a. With cART, most levels in PHIV approached those of PHEU. Among PHIV, better control of HIV was associated with decreases in IL-18 and sTNF-R2 levels.

Poster Abstracts

1075 Early Treated Children With Perinatal HIV Show Elevated Monocyte Activation Into Late Childhood Claire Davies 1 , Steve Innes 1 , Florin Vaida 2 , Bin Tang 2 , Kennedy Otwombe 3 , Mark Cotton 4 , Sara Browne 2 , Patrick Bouic 1 1 Stellenbosch University, Cape Town, South Africa, 2 University of California San Diego, La Jolla, CA, USA, 3 Perinatal HIV Research Unit, Soweto, South Africa, 4 Family Clinical Research Unit, Tygerberg, South Africa Background: Early ART within 3 months of birth has dramatically improved long-term outcomes in children living with perinatal HIV. However, these children face decades of HIV-associated immune dysregulation and chronic inflammation. Neither the long-term inflammatory profile nor the risk of long term non-communicable diseases are well understood. We assessed biomarkers associated with inflammation (monocyte and lymphocyte), metabolic and cardiovascular damage and response markers in early-treated children compared to controls unexposed to HIV. Methods: 175 children (66 with HIV, 109 unexposed to HIV) aged 7-12 years and previously part of CHER and P1060 trials were followed at Tygerberg Children’s Hospital, South Africa. Children with HIV initiated ART within 3 months of birth, were seen 3-monthly for clinical care, were virologically suppressed (>90% suppression), had preserved CD4+ cell counts and were asymptomatic. Unexposed children arose from the same communities and socio-economic

1074 Inflammation Phenotypes in Children With Perinatally Acquired HIV in South Africa Claire Davies 1 , Steve Innes 1 , Patrick Bouic 1 , Bin Tang 2 , Kennedy Otwombe 3 , Mark Cotton 4 , Sara Browne 2 , Florin Vaida 2 1 Stellenbosch University, Cape Town, South Africa, 2 University of California San Diego, La Jolla, CA, USA, 3 Perinatal HIV Research Unit, Soweto, South Africa, 4 Family Clinical Research Unit, Tygerberg, South Africa Background: Children with perinatally acquired HIV face increased risk of cardiovascular disease due to chronic inflammation. As these children enter

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