We analyzed single nucleotide polymorphisms in the 5′-untranslated region (-44C/G and -52G/A) of the beta-defensin-1 gene in 78 Mozambican HIV-1-infected mothers. We observed significantly lower levels of HIV-1 RNA in breast milk, but not in plasma, in women with the -52GG genotype versus women with the -52GA and -52AA genotypes, supporting the hypothesis that different expression of β-defensins could have an impact on viral replication in breast milk.