Human leucocyte antigen-DP presents peptides to CD4 T cells and plays an important role in parasitic infections and autoimmune diseases, yet its influence on HIV-1 susceptibility has not been well studied. Here, we report several human leucocyte antigen-DP genotypes associated with HIV-1 susceptibility in Kenyan sex workers. Among these, one common genotype stands out. DPA1*010301 (frequency = 60.4%) was associated with HIV-1 resistance (P = 0.033, odds ratio = 1.585, 95% confidence interval = 1.036-2.425) and slower seroconversion (P = 0.001, log rank = 0.595, 95% confidence interval = 0.433-0.817). The discovery of common human leucocyte antigen-DP genotypes contributing to HIV-1 immunity may help overcome difficulties encountered with highly polymorphic human leucocyte antigens.