Martes, 24 de marzo de 2026

Avendaño J, Ventosa J, Rodríguez C, Morales D, Muñoz R, Pavía N, Navarro ML, Holguín Á. Perinatal HIV exposure is associated with long-term alterations in immune marker levels in children

J Infect Public Health. 2026

"This study emphasizes the need to understand the long-term immune effects of HIV/ART exposure to improve health outcomes for HIV-exposed and uninfected children globally". - Dr. África Holguín

Summary:

Background: HIV-exposed uninfected (HEU) children represent a little-studied growing population. We aimed to determine whether perinatal HIV exposure imparts long-term immune alterations.

Methods: A prospective cohort including 91 children (<13 years) from México was classified into four groups: HIV unexposed-uninfected (HUU, n = 25), HEU (n = 25), HIV exposed infected with undetectable (HEI^undetVL, n = 25) or detectable VL (HEI^detVL, n = 16). Sixty-four immune biomarkers were measured in each child: 55 proteins in plasma and 9 mRNAs in paired-dried blood samples RESULTS: Principal Component Analysis revealed that HEU exhibited similarity to HEI^undetVL and higher inter-individual variability than HUU. HEU children exhibited significantly higher levels of IL-17A, TIM-3, P-Selectin and CD14 mRNA along with lower levels in Serum amyloid A (SAA), IGFBP-4, myeloperoxidase and tPA compared with HUU. Despite no differences in age at diagnosis, CD4 counts, or ART exposure time between the HIV-exposed and infected groups, active infection (HEI^detVL) was associated with significant alterations in 15 markers, indicating extensive immune dysregulation. These included higher levels of myeloid activation markers (sCD14, sCD163), chemokines (CXCL10), VEGF-A, immune-checkpoints (Galectin-9, PD-1 mRNA) and markers of vascular inflammation and coagulation (tPA, ICAM-1, myeloperoxidase, N-GAL, or SAA), as well as lower levels of four immune-checkpoints (sCD86, sCD137, CTLA-4) and MMP-2, compared with HEI^undetVL. Logistic regression models identified SAA, TIM-3 and IGFBP-4 as independently associated with HIV exposure, achieving an accuracy of 82 % in classifying HEU vs. HUU children, whereas downregulated sCD86, combined with elevated Galectin-9 and VEGF-A levels, were independently associated with active HIV viremia, with a classification accuracy of 92.7 %.

Conclusions: Perinatal HIV exposure induces persistent immune alterations, even in uninfected children, including elevated cytokines, immune-checkpoints, thrombosis and vascular inflammation markers. These findings suggest that, even without acquiring HIV, exposed children exhibit immunological imprints that may contribute to increased risk of adverse health outcomes.

Why do you highligth this publication?

The results of this study not only open new research challenges, but also underscore the importance of ongoing medical follow-up for children exposed to HIV who are born uninfected, ensuring they receive the necessary support for a healthy and fulfilling life. Given the global expansion of the HIV-exposed uninfected population, identifying these specific immune signatures is crucial for risk stratification and the development of targeted long-term health interventions.