Toll-like receptor polymorphism associations with HIV-1 outcomes among sub-Saharan Africans.

OBJECTIVE We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples. METHODS Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls. RESULTS TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR] = 0.7; P = .03 and OR = 0.9, P = .5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression. CONCLUSIONS TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships.