HLA and HIV-1 : Heterozygote advantage and B35-Cw04 disadvantage

• Published in: Science (American Association for the Advancement of Science) Vol. 283; no. 5408; pp. 1748 - 1752
• Main Authors: CARRINGTON, M, NELSON, G. W, MARTIN, M. P, KISSNER, T, VLAHOV, D, GOEDERT, J. J, KASLOW, R, BUCHBINDER, S, HOOTS, K, O'BRIEN, S. J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 12.03.1999; The American Association for the Advancement of Science
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome (AIDS); Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - immunology; Adult; AIDS; AIDS/HIV; Alleles; Antigen Presentation; Bacteriology; Biological and medical sciences; Cohort Studies; Communicable Diseases; Disease Progression; Ethnic Groups; Fundamental and applied biological sciences. Psychology; Genes; Genes, MHC Class I; Genetic Predisposition to Disease; Genetics; Heterozygote; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV Long-Term Survivors - statistics & numerical data; HIV patients; HIV-1; HLA Antigens - genetics; HLA class II antigens; HLA-B Antigens - genetics; HLA-C Antigens - genetics; Homozygote; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Infection; Killer Cells, Natural - immunology; Loss of Heterozygosity; Major histocompatibility complex; Medical research; Microbiology; Patients; Population Distribution; Population Education; Proportional Hazards Models; Risk; Human; Immunopathology; HIV-1 virus; Major histocompatibility system; Retroviridae; AIDS; Immune deficiency; Lentivirus; Survival; Heterozygosity; Virus; Infection; Immunogenetics; Sensitivity resistance; Viral disease; Genetics; Human immunodeficiency virus; Genetic association; Class I histocompatibility antigen; HLA-B-Locus
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.283.5408.1748

A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.