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

BACKGROUND: Reports 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. METHODS: Study 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. RESULTS: At 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/mm(3), 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. CONCLUSIONS: These 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.