HIV-exposed-uninfected infants have increased inflammation and monocyte activation

AIDS. 2019 Apr 1;33(5):845-853. doi: 10.1097/QAD.0000000000002128.


Background: HIV-exposed-uninfected (HEU) infants have increased infectious morbidity and mortality; little is known about their levels of inflammation and monocyte activation.

Methods: Plasma samples obtained at birth and 6 months from 86 HEU mother-infant pairs enrolled in the National Institute of Child Health and Human Development cohorts in Brazil were compared with 88 HIV-unexposed mother-infant pairs. HIV-infected mothers received antiretroviral therapy during pregnancy, their infants received zidovudine prophylaxis and were not breastfed. IL-6, soluble TNFα receptor I (sTNF-RI) and II, soluble CD14, soluble CD163, IFN-γ-induced protein 10 (IP-10), vascular cell adhesion molecule, oxidized LDL, D-dimer and high-sensitivity C-reactive protein were assayed by ELISA at birth and at 6 months. sTNF-RI and IL-6 were considered coprimary endpoints.

Results: Among HIV-infected mothers, 79% had HIV-RNA less than 400 copies/ml prior to delivery. Compared with HIV-unexposed, HEU infants had a lower mean gestational age (38.7 vs. 39.3 weeks) and weight (3.1 vs. 3.3 kg); and reached lower weight (5.9 vs. 8.5 kg) and height (53.6 vs. 68.8 cm) at 6 months. With the exception of vascular cell adhesion molecule, inflammatory markers were generally higher (P ≤ 0.005) in HEU at birth, but at 6 months only sTNF-RI and IL-6 remained higher. For HEU pairs, only IP-10 was associated with maternal levels at birth (P < 0.001). In HEU, elevated levels of high-sensitivity C-reactive protein and IP-10 at birth were associated with lower weight at birth (P = 0.04) and at 6 months (P = 0.04).

Conclusion: HIV-exposed infants have heightened inflammation and monocyte activation at birth, which for some markers persisted to 6 months of life and was not related to maternal inflammatory status. Inflammation may contribute to the increased HEU infectious morbidity and poor growth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Brazil / epidemiology
  • Female
  • HIV Infections / blood
  • HIV Infections / immunology*
  • Humans
  • Immunophenotyping
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Inflammation / blood
  • Inflammation / immunology*
  • Inflammation / virology
  • Longitudinal Studies
  • Male
  • Monocytes / immunology*
  • Mothers*
  • Oxidative Stress / immunology*
  • Pregnancy
  • Pregnancy Complications, Infectious / blood
  • Pregnancy Complications, Infectious / immunology*
  • Pregnancy Complications, Infectious / virology*


  • Biomarkers