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Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 936-941
Combined Genotypes of CCR5, CCR2, SDF1, and HLA Genes Can Predict
the Long-Term Nonprogressor Status in Human Immunodeficiency
Virus-1-Infected Individuals
Magdalena Magierowska,
Ioannis Theodorou,
Patrice Debré,
Françoise Sanson,
Brigitte Autran,
Yves Rivière,
Dominique Charron,
French ALT,
IMMUNOCO Study Groups, and
Dominique Costagliola
From the Laboratoire d'Immunologie Cellulaire et Tissulaire, UMR
CNRS 7627, Hôpital Pitié-Salpêtrière, Paris;
URA CNRS 1157, Institut Pasteur, Paris; Laboratoire d'Immunologie,
Hôpital Saint-Louis, Paris; and INSERM SC4, IFR Saint-Antoine de
recherche en Santé, Paris, France.
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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