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Carrington, Mary; Nelson, George W.; Martin, Maureen P.; Kissner, Teri; Vlahov, David; Goedert, James J.; Kaslow, Richard; Buchbinder, Susan; Hoots, Keith; O'Brien, Stephen J.
Science (American Association for the Advancement of Science), 03/1999, Volume: 283, Issue: 5408Journal Article
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.
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