Elevated Concentrations of Milk β2-Microglobulin Are Associated with Increased Risk of Breastfeeding Transmission of HIV‑1 (Vertical Transmission Study)

There is increasing
evidence to support a relationship between
human immunodeficiency virus (HIV-1) transmission through breastfeeding
and milk host factors. We analyzed skim milk proteome to further determine
the contribution of host factors to the risk of mother-to-child transmission
of HIV-1. Quantitative mass spectrometry analysis was performed on
nine case–control pairs of HIV+ transmitter/nontransmitter
mothers, and specific biochemical assays on two selected proteins
were assessed in an independent validation set of 127 samples. 33
identified proteins were differentially expressed between HIV+ transmitter
and nontransmitter mothers. Among them, β2-microglobulin was
significantly higher in the maternal transmitter than in the nontransmitter
groups (p value = 0.0007), and S100A9 was significantly
higher in the early maternal transmitter cases (before 4 months of
age) compared with the nontransmitters (p value =
0.004). β2-Microglobulin correlated with milk and plasma HIV
viral load and CD4+ cell count, whereas S100A9 correlated with the
estimated timing of infection of the infant through breastfeeding.
Finally, β2-microglobulin concentration in milk could accurately
predict the risk of HIV-1 postnatal transmission by breastfeeding
(p value < 0.0001, log-rank test). In conclusion,
milk β2-microglobulin and S100A9 are host factors that are found
to be associated with mother-to-child transmission of HIV-1.