Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission

Abstract

Understanding how the level of human immunodeficiency virus type 1 (HIV-1)-infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1-infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R=.144; P=.032), levels of cell-free virus in blood plasma (R=.365; P<.001), and the detection of proviral DNA in cervical and vaginal secretions (P<.001 and P = .030, respectively). The number of infected BMCs per million cells was lower in colostrum or early milk than in mature milk (P<.001). Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P<.001). Each log10 increase in infected BMCs per milliliter was associated with a 3.19-fold-increased risk of transmission (P=.002), after adjustment for cell-free virus in plasma (hazard ratio [HR], 2.09; P=.03) and breast milk (HR, 1.01; P=1.00). This suggests that infected BMCs may play a more important role in transmission of HIV via breast-feeding than does cell-free virus.

Figure 1

Correlation of the no. of HIV-1–infected breast milk cells (BMCs) per million cells with the concentration of cell-free virus per milliliter of breast milk (A) and cell-free virus per milliliter of maternal blood plasma (B) among breast-feeding mothers. Correlation coefficients and significance levels are shown at the upper left.

Figure 2

Distribution of levels of HIV-1 in breast milk from transmitting and nontransmitting mothers, by time interval. The no. of infected breast milk cells (BMCs) per million cells (A) and the no. of infected BMCs per milliliter (B) were compared between transmitting and non-transmitting mothers. The nos. of samples analyzed and the months of each scheduled visit are shown below the box plots. P values are shown above the corresponding box-plot pair. The upper and lower bars of each box plot represent the maximum and minimum values, respectively; the horizontal bar at the center of each box plot represents the median value; and the top and bottom of each box plot represent the 75th and 25th percentiles, respectively. Among transmitting mothers, transmission may have occurred at any time during or after delivery.

Figure 3

Changes in levels of HIV-1 in breast milk over time. The mean no. of infected breast milk cells (BMCs) per million cells, the mean concentration of infected BMCs per milliliter, and the mean no. of cell-free virus particles per milliliter of breast milk are shown. The upper and lower bars of each box plot represent the maximum and minimum values, respectively; the horizontal bar at the center of each box plot represents the mean value; and the top and bottom of each box plot represent the 75th and 25th percentiles, respectively.