Human leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8 + T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC - II -encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR–RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 ( C/T intron 7 ) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06–1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56–7.46), P = 0.0010] variants of TAP2 ( A/G exon 11 ) ( T665A ) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case–control analysis might suggest a possible role of TAP2 ( A/G exon 11 ) ( T665A ) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.