Background:  Although HIV transmission through breastfeeding is of great public health importance, the mechanisms underlying transmission are not well understood. Interleukin (IL) -7 has been shown to enhance HIV transmission and replication in vitro, but its effect on HIV transmission in vivo is unknown. We tested whether breast milk IL-7 concentration influences postnatal HIV transmission.

Methods:  A nested case-control study was undertaken within a cohort of women recruited in Lusaka, Zambia. We compared IL-7 concentrations in breast milk samples from 24 HIV-infected breastfeeding women who transmitted HIV to their child after the neonatal period and 47 women who did not transmit. We also tested breast milk samples from 18 HIV-uninfected mothers. Samples were frequency-matched by the time of sample collection (1 week and 1 month post-partum). Breast milk viral load, sodium, and IL-7 concentrations, as well as maternal CD4 counts, plasma viral load and plasma IL-7 concentrations were measured. Logistic regression was used for adjusted analyses.

Results:  Concentrations of IL-7 in breast milk were >10-fold higher than in plasma, with an overall median of 158 pg/mL (range <0.25 pg/mL to 0.16 mg/mL). Among HIV-infected non-transmitting mothers, breast milk IL-7 concentrations exhibited a bimodal distribution with one peak at about 280 pg/mL and a second peak at low or undetectable levels (<2.5 pg/mL). To separate the 2 peaks, an IL-7 cutoff level of 30 pg/mL was chosen. IL-7 levels below this cutoff were significantly associated with less HIV transmission (odds ratio, OR, 0.13, 95%CI 0.03 to 0.64). This association remained significant after adjustment for breast milk viral load and maternal CD4 cell counts (adjusted OR 0.10, 95%CI 0.02 to 0.62). Low to undetectable IL-7 levels among the non-transmitters were also more frequent in 1-month than 1-week samples and were associated with higher parity. Adjusting for parity and time of sample collection did not modify the association.

Conclusions:  These findings suggest that normal or high IL-7 concentrations facilitate effective HIV transmission through breastfeeding. They are concordant with previous findings that IL-7 promotes productive infection of quiescent T-cells in vitro. Normal or high breast milk IL-7 concentrations in vivo may enhance susceptibility of quiescent infant T cells to HIV infection.