Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding

Abstract

Background: The inefficiency of HIV breast-milk transmission may be caused by the presence of immunologically active factors, including human milk oligosaccharides (HMOs).

Objective: We investigated whether HMO concentrations are associated with a reduced risk of postnatal HIV transmission.

Design: A nested case-control study was conducted within a larger cohort study of HIV-infected women and their infants followed from birth to 24 mo in Lusaka, Zambia. Breast-milk samples collected at 1 mo from 81 HIV-infected women who transmitted via breastfeeding, a random sample of 86 HIV-infected women who did not transmit despite breastfeeding, and 36 uninfected breastfeeding women were selected. Total and specific HMO concentrations were measured by HPLC and compared between groups with adjustment for confounders by using logistic regression.

Results: HIV-infected women with total HMOs above the median (1.87 g/L) were less likely to transmit via breastfeeding (OR: 0.45; 95% CI: 0.21, 0.97; P = 0.04) after adjustment for CD4 count and breast-milk HIV RNA concentrations; a trend toward higher concentrations of lacto-N-neotetraose being associated with reduced transmission (OR: 0.49; 95% CI: 0.23, 1.04; P = 0.06) was also observed. The proportion of 3'-sialyllactose (3'-SL) per total HMOs was higher among transmitting than among nontransmitting women (P = 0.003) and correlated with higher plasma and breast-milk HIV RNA and lower CD4 counts. Neither Secretor nor Lewis status distinguished between transmitting and nontransmitting women.

Conclusions: Higher concentrations of non-3'-SL HMOs were associated with protection against postnatal HIV transmission independent of other known risk factors. Further study of these novel, potentially anti-HIV components of breast milk is warranted.

Trial registration: ClinicalTrials.gov NCT00310726.

FIGURE 1.

HMO HPLC spectra of representative samples from a Lewis-positive Secretor woman (A), a Lewis-negative Secretor woman (B), and a Lewis-positive non-Secretor woman (C). Peak annotation (R: raffinose; 1: 2′-fucosyllactose; 2: 3 -fucosyllactose; 3: lacto-N-neotreaose; 4: 3′-sialyllactose; 5: lacto-N-tetraose; 6: lacto-N-fucopentaose I; 7: lacto-N-fucopentaose II; 8: lacto-N-fucopentaose III). D: Secretor women express the α1–2-fucosyltransferase FUT2, which participates in the biosynthesis of characteristic 2′-FL (peak 1) or LNFP I (peak 6). Women with active Lewis gene express the α1–3/4-fucosyltransferase FUT3, which participates in the biosynthesis of characteristic α1–4-LNFP II (peak 7). Dark circles: glucose; light circles: galactose; squares: N-acetylglucosamine; triangles: fucose. HMO, human milk oligosaccharides; Le⁺, Lewis positive; Le^–, Lewis negative; LNFP, lacto-N-fucopentaose; Se⁺, Secretor positive; Se^–, Secretor negative; 2′-FL, 2′-fucosyllactose.

FIGURE 2.

Scatter plots of total HMO (g/L) by proportion of each oligosaccharide per total HMO among 167 HIV-infected mothers. Spearman's coefficients (ρ) and P values are shown. HMO, human milk oligosaccharide; LNFP, lacto-N-fucopentaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetraose; 2′-FL, 2′-fucosyllactose; 3-FL, 3-fucosyllactose; 3′-SL, 3′-sialyllactose.

FIGURE 3.

Scatter plots of total HMO and percentage of 3′-SL per total HMO by CD4 cell count plasma viral load and breast-milk HIV RNA viral load at 1 mo among 167 HIV-infected mothers. Spearman's coefficients (ρ) and P values are shown. BM, breast milk; HMO, human milk oligosaccharide; 3′-SL, 3′-sialyllactose.