Nature Medicine
2, 405 - 411 (1996)
doi:10.1038/nm0496-405
Influence of combinations of human major histocompatibility complex genes on the course of HIV−1 infectionR.A. Kaslow1, 10, M. Carrington2, R. Apple3, L. Park4, A. Muñoz4, A.J. Saah4, J.J. Goedert5, C. Winkler2, S.J. O'Brien6, C. Rinaldo7, R. Detels8, W. Blattner5, J. Phair9, H. Erlich3
& D.L. Mann6
1University of Alabama at Birmingham, School of Public Health, Department of Epidemiology, 212C Tidwell Hall, 720 20th Street South, Birmingham, Alabama 35294-0008, USA
2BCDP-SAIC, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA
3Human Genetics Department, Roche Molecular Systems, Inc., Alameda, California 94501, USA
4Department of Epidemiology, the Johns Hopkins School of Hygiene and Public Health, 624 North Broadway, Baltimore, Maryland 21205, USA
5Viral Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, EPN Room 434, 6130 Executive Boulevard, Rockville, Maryland 20852-7370, USA
6Laboratory of Viral Carcinogenesis, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA
7Department of Pathology, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA
8Department of Epidemiology, UCLA School of Public Health, Center for the Health Sciences Room 71-267,10833 Le Conte Avenue, Los Angeles, California 90024-1772, USA
9Department of Medicine, Northwestern Medical School, Comprehensive AIDS Center, 680 North Lake Shore Drive, Suite 1106, Chicago, Illinois 60611-4402, USA
10Correspondence should be addressed to R.A.K. Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV−1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV−1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV−1 and other infections.
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