Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

Abstract

BackgroundReports of increased morbidity and mortality from infectious diseases among HIV Exposed Uninfected (HEU) infants have raised concern about a possible underlying immunodeficiency among them. The objective of this study was to assess the immunological profile of HEU infants born to mothers exhibiting different levels of HIV-1 viremia at the time of delivery.MethodsStudy subjects were enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+ B cell counts were assessed at 2 and 6 months of age, and compared among HEU infants in groups defined by maternal viral load (VL) at the time of delivery (VL < 50 copies/ml, VL 50–1000 copies/ml, and VL > 1000 copies/ml) in a multivariable analysis.ResultsAt 2 months of age, infants born to mothers with VL > 1000 copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884 vs. 2432 cells/mm3, p = 0.02). These differences remained significant after adjusting for maternal and infant antiretroviral drug use, gender, race and gestational age, and persisted at 6 months of age. There were no differences in CD8+ T cell count or absolute CD19+ B cell count between groups, though higher CD19+ B cell percentage was seen among infants born to mothers with VL > 1000 copies/ml.ConclusionsThese results suggest that exposure to high levels of HIV-1 viremia in utero, even in the absence of perinatal transmission, may affect the infant’s developing immune system. While further work needs to be done to confirm these findings, they reinforce the need for optimal treatment of HIV infected pregnant women, and careful follow-up of HEU infants.

Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

“…We report significantly higher peripheral frequencies of cells resembling MDSC, in HIV uninfected children born to mothers with HIV infection (HEU), compared to unexposed controls. Increased disease susceptibility of HEU children have been attributed to HIV‐specific T cell responses, primed by maternal HIV antigens, the immaturity or immunosuppressive state of infants’ adaptive immune system or excessive immune activation in the HIV infected mother . Considering the previously reported potent immunosuppressive abilities of MDSCs , our findings could suggest an additional description of the vulnerability of the HEU child's immune system, driven by regulatory innate immune cells.…”

“…Importantly, evidence show that HEU children are at greater risk to acquire and succumb to infectious diseases, when compared with children of uninfected mothers. The mechanisms underlying increased susceptibility and dissemination of TB in HEU children, is not fully understood, but it is suggested that immaturity of infant immune cells , in‐utero exposure to HIV antigens , immune activation of the , may drive these changes .…”

Maternal HIV infection is an important health determinant in non-HIV-infected infants

“…Offspring born to women with advanced HIV infection and eventually at higher risk of maternal mortality during childhood might be particularly vulnerable. In addition to an adverse social and economic background, compared with healthy mothers, those who are immunodeficient or clinically unwell might be less able to provide appropriate child care, adequate duration of breastfeeding or more likely to carry infectious pathogens harmful to their infants [49,50].…”

Maternal HIV infection alters the immune balance in the mother and fetus; implications for pregnancy outcome and infant health

“…First the virus, including viral proteins, may have a direct proinflammatory effect on placental cells as well as on the developing infant's immune system. Correlations have been described between maternal viral load and the infant's CD4 þ T-cell count [101]. The virus may be recognized as foreign by components of the fetal immune system and induce inflammation, whereas at the same time viral proteins transferred across the placenta could have individual effects.…”