We carried out an association study of DC-SIGN polymorphism in 197 infants born to ART-naive HIV-1-infected mothers recruited in Harare, Zimbabwe [20] . Among them, 97 were HIV-1-infected and 100 were uninfected. Of the 97 HIV-1-infected infants, 57 were infected IU, 11 IP, and 17 PP. Timing of infection could not be determined for 12 HIV-1-infected infants as specimens were not available at some time points. Baseline characteristics of mothers and infants were reported previously [22] . Briefly, maternal age and CD4 + T cell count, child sex, mode of delivery, duration of membrane rupture and gestational age were similar among all groups. Maternal viral load .29 000 copies/ml was associated with increased risk of both IU and PP HIV-1 transmission, OR: 3.64, 95% CI: 1.82-7.31, P = 0.0002 and OR: 4.45, 95% CI: 1.50-13.2, P = 0.0045, respectively. Ten htSNPs from the 20 SNPs ( Figure 1A ) corresponding to the 10 major DC-SIGN haplotypes ( Figure 1B) previously described among Zimbabweans [23] , were genotyped in the study samples. Haplotypes with frequencies above 5% in the study population were analysed for their potential association with MTCT of HIV-1. Infants carrying H4 or H6 haplotypes had increased risk of IU HIV-1-infection, whereas H2 haplotype carriers were less likely to be infected during pregnancy compared to infant noncarriers ( Table 1) . None of the haplotypes were significantly associated with altered risks of IP or PP infections. The H4 and H6 hapotypes remained significantly associated with IU HIV-1 infection (OR: 4.98, 95% CI: 1.32-18.8, P = 0.0168 and OR: 2.93, 95% CI: 1.27-6.76, P = 0.0113, respectively) after adjustment was made for maternal viral load. H2 haplotype remained significantly associated with protection against IU infection after adjustment for maternal viral load (OR: 0.23, 95% CI: 0.10-0.51, P = 0.0003). To identify the causal SNPs associated with increased IU transmission of HIV-1, we determined the association between IU HIV-1 infection and each of H4 and H6 signature SNPs. Promoter p-201A (rs11465366) and exon 4 198Q (rs41374747) variants are found exclusively in H6 while exon 4 242V (rs11465380) variant tag H4 ( Figure 1B) . Both H4 and H6 haplotypes harbour promoter variant p-336C (rs4804803) that is known to influence DC-SIGN promoter activity [25] and increased risk of HIV-1 parenteral infection [29] . These variants were all associated with increased risk of IU HIV-1 infection after adjustment for maternal viral load (Table 2 ). In a step-wise logistic regression analysis including all DC-SIGN associated SNPs and maternal viral load, DC-SIGN 242V variant (OR: 4.87, 95% CI: 1.19-19.9, P = 0.0261) and maternal viral load (OR: 3.30, 95% CI: 1.48-7.37, P = 0.0033) remained independent predictors of HIV-1 IU acquisition. Maternal DC-SIGN haplotypes were not associated with MTCT of HIV-1 (Table S2) .