Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1–infected individuals

M Magierowska, I Theodorou, P Debré… - Blood, The Journal …, 1999 - ashpublications.org
M Magierowska, I Theodorou, P Debré, F Sanson, B Autran, Y Rivière, D Charron, F ALT…
Blood, The Journal of the American Society of Hematology, 1999ashpublications.org
Abstract Human immunodeficiency virus (HIV)-1–infected long-term nonprogressors (LT-NP)
represent less than 5% of HIV-1–infected patients. In this work, we tried to understand
whether combined genotypes of CCR5-▵ 32, CCR2-64I, SDF1-3′ A and HLA alleles can
predict the LT-NP status. Among the chemokine receptor genotypes, only the frequency of
the CCR5-▵ 32 allele was significantly higher in LT-NP compared with the group of standard
progressors. The predominant HLA alleles in LT-NP were HLA-A3, HLA-B14, HLA-B17, HLA …
Abstract
Human immunodeficiency virus (HIV)-1–infected long-term nonprogressors (LT-NP) represent less than 5% of HIV-1–infected patients. In this work, we tried to understand whether combined genotypes of CCR5-▵32, CCR2-64I, SDF1-3′A and HLA alleles can predict the LT-NP status. Among the chemokine receptor genotypes, only the frequency of the CCR5-▵32 allele was significantly higher in LT-NP compared with the group of standard progressors. The predominant HLA alleles in LT-NP were HLA-A3, HLA-B14, HLA-B17, HLA-B27, HLA-DR6, and HLA-DR7. A combination of both HLA and chemokine receptor genotypes integrated in a multivariate logistic regression model showed that if a subject is heterozygous for CCR5-▵32 and homozygous for SDF1 wild type, his odds of being LT-NP are increased by 16-fold, by 47-fold when a HLA-B27 allele is present with HLA-DR6 absent, and by 47-fold also if at least three of the following alleles are present: HLA-A3, HLA-B14, HLA-B17, HLA-DR7. This model allowed a correct classification of 70% of LT-NPs and 81% of progressors, suggesting that the host’s genetic background plays an important role in the evolution of HIV-1. The chemokine receptor and chemokine genes along with the HLA genotype can serve as predictors of HIV-1 outcome for classification of HIV-1–infected subjects as LT-NPs or progressors.
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