Associations of CCR5, CCR2, and Stromal Cell–Derived Factor 1 Genotypes with Human Immunodeficiency Virus Disease Progression in Patients Receiving Nucleoside Therapy

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Abstract
Genotype data for CCR5, CCR2, and stromal cell–derived factor 1 (SDF-1) were obtained from 354 human immunodeficiency virus type 1 (HIV-1)–positive subjects who were being treated with nucleosides. Associations with HIV-1 load, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progression were analyzed. No differences in HIV-1 load or CD4 cell count were observed between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deletion (Δ32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P=.01). In a multivariate analysis, heterozygous CCR5 Δ32 was associated with reduced hazard of progression (hazard ratio, 0.32; P=.02). Subjects homozygous for the SDF-1 3′A variant had more-rapid disease progression (P=.008). The SDF-1 homozygous 3′A variant was related to more-rapid disease progression, and CCR5 Δ32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subjects

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