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.

The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.

We tested the hypothesis that Human Milk Oligosaccharides (HMO) partially account for the inefficiency of HIV transmission through breastfeeding. Using a case‐control design, we measured HMO by HPLC in breast milk samples of 81 HIV‐infected mothers who transmitted HIV via breastfeeding, 86 HIV‐infected mothers who did not transmit and 36 uninfected mothers recruited in Lusaka, Zambia. Only single‐dose nevirapine was used as prophylaxis. Concentration of the individual HMO 3′‐sialyllactose (3′SL) and lacto‐N‐neo‐tetraose was higher in HIV‐infected vs. uninfected mothers. HIV‐infected mothers with concentrations of combined HMO above the median (1.87 g/L) were significantly less likely to transmit via breastfeeding (odds ratio [OR] 0.45[0.21, 0.97], p=0.04) after adjusting for CD4 count and breast milk viral load. Percent HMO that was 3′SL was higher among transmitting vs. non‐transmitting mothers (p=0.005) and correlated with plasma and breast milk viral load and lower CD4 counts. Higher concentrations of HMO and lesser %3′SL were associated with protection against postnatal HIV transmission. Further study of these novel potentially anti‐HIV components of breast milk is warranted.