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Publications

Journal Article Ahead of print

PubMed: 41747457 DOI: 10.1016/j.jiph.2026.103168

Perinatal HIV exposure is associated with long-term alterations in immune marker levels in children.

J Infect Public Health 19(4):103168

Authors: José Avendaño-Ortiz, Judit Ventosa-Cubillo, Concepción Rodríguez-Jiménez, Dulce Morales-Pérez, Rocío Muñoz-Hernández, Noris Pavía-Ruz, María L Navarro, África Holguín

Affiliations

  • Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
  • Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
  • Clínica de Inmunodeficiencias, Departamento de Infectología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
  • Clínica de atención para niños con VIH, UNAM/HGM, Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Clínica de Inmunodeficiencias, Departamento de Infectología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico; Clínica de atención para niños con VIH, UNAM/HGM, Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitario Gregorio Marañón, and Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Universidad Complutense de Madrid (UCM), Madrid, Spain.
  • Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; CIBERESP, Instituto de Salud Carlos III, Madrid, Spain.

Abstract

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.

MeSH

Cd4 Lymphocyte Count, Vascular Endothelial Growth Factor A, Hiv, Peroxidase, Communicable Diseases, Child