In the index partners KIR2DS4*001, the only KIR2DS4 allele to encode a full length receptor, was associated with higher rates of HIV-1 transmission (OR = 2.40, 95% CI = 1.31-4.39, p = 0.003) by logistic regression. Survival analysis for KIR2DS4*001 demonstrated accelerated transmission of HIV-1 (RH = 1.72, p = 0.005). This allele in the seronegative partners was not associated with acquisition. The KIR2DS4*001 allele was also associated with a high VL (0.17 ± 0.08 log10, p < 0.05). No association was observed with its ligand, HLA-Cw*04, or with the HLA-Cw*04/KIR2DS4*001 combination. Previously reported findings on other KIR genes could not be confirmed.