Specific Human Leukocyte Antigen Alleles Associated With HIV-1 Infection in an Indian Population

Abstract

Since the beginning of the AIDS epidemic evidence has accumulated that genetic factors are involved in the pathogenesis of the disease. The role of host genes in the course of HIV-1 infection has been examined in different populations and among all major risk groups. Human leukocyte antigen (HLA) associations with HIV progression correlate well with the interaction between the pathogen and host. Most HLA polymorphisms are concentrated in the region that determines specificity for foreign peptide presentation. Three models have been proposed to explain maintenance of the HLA polymorphism: (1) balancing selection where alleles confer resistance to one disease but confer susceptibility to another; (2) heterozygote advantage where a unique HLA type increases the breadth of peptide recognition and thereby immune defense against infectious organisms; and (3) frequency-dependent selection where a pathogen evolves to escape an efficient immune response mediated by common alleles in the population butremains susceptible to responses mediated by low-frequency alleles. Each of these mechanisms has probably been operative under various host or environmental circumstances. Any change in primary structure may throttle a neutral allele into a deleterious one. HLA associations with HIV disease may be particularly apparent on investigation because the recent epidemic has not had enough time to show diminished frequencies of deleterious alleles. The paucity of data on the association of HLA alleles with the predominant HIV-1 subtype C in India motivated us to undertake the present study. (excerpt)