HIV-exposed uninfected (HEU) infants continue to experience increased morbidity/mortality from infectious causes compared with infants born to HIV-uninfected women. To explore possible immune etiologies, we conducted an immune profiles analysis, comparing profiles from a Botswana-based cohort of HEU to HIV-unexposed (HU) infants.
Multiparametric flow cytometry was used to quantify proportions and phenotypic characteristics of innate immune cells (monocytes, dendritic cells and NK cells) and adaptive T and B cell-mediated immune responses using peripheral blood mononuclear cells (PBMCs) collected at 3-months of life from HEU and HU infants enrolled in a longitudinal gut microbiome study in Botswana. All HIV-infected women received ≥6 weeks of ART prior to delivery. All infants were born full-term and all HEU infants tested HIV negative at 3 months of life.
Thirty-three infants (17 HEU and 16 HU) were studied cross-sectionally. HEU infants had lower proportions CD14+ monocytes compared with HU infants (p=0.013). The proportion of CD14+ CD16- ‘classical’ monocytes was significantly reduced in HEU infants, while proportions of CD14+ CD16+ non-classical/intermediate monocytes, associated with increased activation and inflammatory responses, were markedly increased (Figure). Proportions of NK cells, the primary innate immune system effector cell, were lower in HEU infants (p=0.026). Upregulation of NKp30, a surface marker denoting terminal activation, on CD56hiCD16low NK cell subset was noted among PBMCs of HEU infants. Frequencies of CD4+ and CD8+ T cell subsets, proportions of regulatory T cells and expression of immune activation markers on these T cell populations did not differ between groups. Proportion of late memory B cells (Bm5, IgD- CD38-) was lower in HEU infants (p=0.026). While fewer HEU infants exclusively breastfed through 3 months (71% vs 88%), the difference was not significant (p=0.40). Despite these findings, there was no significant difference in hospitalizations in the first year of life between the groups.
In this cohort, in utero exposure to HIV-1 and ART was associated with a distinct immunological profile characterized by increased immune activation in the innate immune system. Longitudinal evaluations are needed to determine whether abnormal innate immune activation among HEU has longer-term clinical consequences.