TY - JOUR
T1 - Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection
AU - MacDonald, Kelly S.
AU - Fowke, Keith R.
AU - Kimani, Joshua
AU - Dunand, Viviane A.
AU - Nagelkerke, Nico J.D.
AU - Ball, T. Blake
AU - Oyugi, Julius
AU - Njagi, Ephantus
AU - Gaur, Lakshmi K.
AU - Brunham, Robert C.
AU - Wade, Judy
AU - Luscher, Mark A.
AU - Krausa, Peter
AU - Rowland-Jones, Sarah
AU - Ngugi, Elizabeth
AU - Bwayo, Job J.
AU - Plummer, Francis A.
N1 - Funding Information:
Grant support: Medical Research Council (MRC) of Canada (GR-13301) and the National Institutes of Health (AI34616). K.S.M. was the recipient of an MRC Canada Research Fellowship and is a Career Scientist of the Ontario HIV Treatment Network. K.F. was the recipient of a National Health Research Development Program studentship. V.A.D. was the recipient of a Swiss National Foundation for Scientific Research Fellowship Grant (84AD-042907). F.A.P. is an MRC Canada Senior Scientist. M.A.L. was the recipient of a Toronto Hospital Skate-the-Dream fellowship.
PY - 2000
Y1 - 2000
N2 - Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P = .0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P = .0003), which suggests that anti- HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.
AB - Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P = .0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P = .0003), which suggests that anti- HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.
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U2 - 10.1086/315472
DO - 10.1086/315472
M3 - Article
C2 - 10823757
AN - SCOPUS:0034120188
SN - 0022-1899
VL - 181
SP - 1581
EP - 1589
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -