HLAand HIV-1: Heterozygote Advantage andB*35-Cw*04Disadvantage
Mary Carrington, George W. Nelson, Maureen P. Martin, Teri Kissner, David Vlahov, James J. Goedert, Richard Kaslow, Susan Buchbinder, Keith Hoots, Stephen J. O'Brien- Multidisciplinary
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. MaximumHLAheterozygosity of class I loci (A,B, andC) 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. TheHLAclass I allelesB*35andCw*04were 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 atHLAclass I loci, to their lacking the AIDS-associated allelesB*35andCw*04, or to both.