HIV-1 is rapidly diversifying in African, Asian and Caucasoid populations, which in parallel display extensive polymorphism of genes encoding class I human leukocyte antigens (HLA). Immune responses mediated by HLA class I molecules are imprinting mutations in HIV-1, which in turn affects HIV-1 diversity. Intra- and inter-ethnic studies have shown reproducible HLA class I allele, haplotype and supertype associations with HIV-1 infection and the development of AIDS (HIV/AIDS). In Caucasoids and Africans, HLA-B57 and related alleles of the B58 supertype associate with low viraemia, delayed onset of AIDS and, possibly, cytotoxic T lymphocyte (CTL)-driven attenuation of HIV-1. In HIV-1-exposed but uninfected Southeast Asians, HLA-A11 has been associated with CTL responses directed against HIV-1 Nef. HLA-A11 displays unique peptide-binding properties and is recognized by natural killer cells utilizing the inhibitory killer Ig-like receptor 3DL2 in a peptide-dependent manner.