Toll-like receptors (TLRs) and defensins (DEFs) play a crucial role in the host's innate immunity and may influence HIV-1 disease progression. We investigated the impact of TLR9 +1174G > A, 1635A > G and DEFβ1 -44C > G, -52G > A single nucleotide polymorphisms on the clinical outcome of 95 HIV-1-infected children. The TLR9 1635AG genotype and TLR9 [G;G] haplotype were associated with rapid disease progression, whereas the DEFβ1 -44CG genotype and DEFβ1 [G;G] haplotype correlated with a better clinical outcome.