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*
Laboratoire de Physiologie Cellulaire, Université Pierre et Marie Curie, Paris, France;
Laboratoire d’Immunologie, Hôpital Necker, Paris, France;
Intramural Research Support Program, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702;
§
Laboratory of Genomic Diversity, National Cancer Institute, Frederick MD 21702;
¶
Service de Cancérologie/SIDA, Hôpital Laennec, Paris, France; and
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Center for Neurovirology and Neurooncology, MCP Hahnemann University of Health Sciences, Philadelphia, PA 19102.
The genetics of resistance to infection by HIV-1 cohort consists of
200 slow and 75 rapid progressors to AIDS corresponding to the extremes
of HIV disease outcome of 20,000 Caucasians of European descent. A
comprehensive analysis of HLA class I and class
II genes in this highly informative cohort has identified HLA alleles
associated with fast or slow progression, including several not
described previously. A quantitative analysis shows an overall HLA
influence independent of and equal in magnitude (for the protective
effect) to the effect of the CCR5-
32 mutation. Among
HLA class I genes, A29
(p = 0.001) and B22
(p < 0.0001) are significantly associated
with rapid progression, whereas B14 (p =
0.001) and C8 (p = 0.004) are significantly
associated with nonprogression. The class I alleles B27, B57, C14
(protective), and C16, as well as B35 (susceptible), are also
influential, but their effects are less robust. Influence of class II
alleles was only observed for DR11. These results confirm the influence
of the immune system on disease progression and may have implications
on peptide-based vaccine development.
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 T. M. Williams Human Leukocyte Antigen Gene Polymorphism and the Histocompatibility Laboratory J. Mol. Diagn., August 1, 2001; 3(3): 98 - 104. [Abstract] [Full Text] [PDF]
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 L. F. Ross Genetic Exceptionalism vs. Paradigm Shift: Lessons from HIV J. Law Med. Ethics, June 1, 2001; 29(2): 141 - 148. [PDF]
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 C. M. Hogan and S. M. Hammer Host Determinants in HIV Infection and Disease: Part 2: Genetic Factors and Implications for Antiretroviral Therapeutics Ann Intern Med, May 15, 2001; 134(10): 978 - 996. [Abstract] [Full Text] [PDF]
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L. F. Ross Genetic Exceptionalism vs. Paradigm Shift: Lessons from HIV J. Law Med. Ethics, March 1, 2001; 29(1): 141 - 148. [PDF]
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S. Goldstein, C. R. Brown, H. Dehghani, J. D. Lifson, and V. M. Hirsch Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+ T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication J. Virol., October 15, 2000; 74(20): 9388 - 9395. [Abstract] [Full Text]
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 S. A. Migueles, M. S. Sabbaghian, W. L. Shupert, M. P. Bettinotti, F. M. Marincola, L. Martino, C. W. Hallahan, S. M. Selig, D. Schwartz, J. Sullivan, et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors PNAS, March 14, 2000; 97(6): 2709 - 2714. [Abstract] [Full Text] [PDF]
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P. O. Flores-Villanueva, E. J. Yunis, J. C. Delgado, E. Vittinghoff, S. Buchbinder, J. Y. Leung, A. M. Uglialoro, O. P. Clavijo, E. S. Rosenberg, S. A. Kalams, et al. Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity PNAS, April 24, 2001; 98(9): 5140 - 5145. [Abstract] [Full Text] [PDF]
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