Associations of CCR5, CCR2, and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy

Genotype data for CCR5, CCR2, and stromal cell-derived factor 1 (SDF-1) wer e obtained from 354 human immunodeficiency virus type 1 (HIV-1)-positive su bjects who were being treated with nucleosides. Associations with HIV-1 loa d, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progr ession were analyzed. No differences in HIV-1 load or CD4 cell count were o bserved between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deleti on (Delta 32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P = .01). In a multivariate analysis, heterozygous CCR5 Delta 32 was associated with reduced hazard of progression (hazard ratio, 0.32; P = .02). Subjects homo zygous for the SDF-1 3'A variant had more-rapid disease progression (P = .0 08). The SDF-1 homozygous 3'A variant was related to more-rapid disease pro gression, and CCR5 Delta 32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subjects.