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

Human immunodeficiency virus (HIV)-1-infected long-term nonprogressors (LT- NP) represent less than 5% of HIV-1-infected patients. In this work, we tri ed to understand whether combined genotypes of CCR5-Delta 32, CCR2-641, SDF 1-3'A and HLA alleles can predict the LT-NP status. Among the chemokine rec eptor genotypes, only the frequency of the CCR5-Delta 32 allele was signifi cantly 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, H LA-DR6, and HLA-DR7. A combination of both HLA and chemokine receptor genot ypes integrated in a multivariate logistic regression model showed that if a subject is heterozygous for CCR5-Delta 32 and homozygous for SDF1 wild ty pe, his odds of being LT-NP are increased by 16-fold, by 47-fold when a HLA -B27 allele is present with HLA-DRG absent, and by 47-fold also if at least three of the following alleles are present: HLA-AB, HLA-B14, HLA-B17, HLA- DR7. This model allowed a correct classification of 70% of LT-NPs and 81% o f progressors, suggesting that the host's genetic background plays an impor tant role in the evolution of HIV-1. The chemokine receptor and chemokine g enes along with the HLA genotype can serve as predictors of HIV-1 outcome f or classification of HIV-1-infected subjects as LT-NPs or progressors. (C) 1999 by The American Society of Hematology.