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.