The effect of polymorphisms on genes encoding the CCR5 chemokine receptor and vitamin D receptor (VDR) in human immunodeficiency virus (HIV) type 1 disease progression was analyzed in a cohort of 185 HIV-seropositive injection drug users. Results confirmed a lack of association in patients with HIV disease between CCR5 wtDelta32 heterozygosity and a slow progression to AIDS and to a CD4 cell count <200 cells/microL. In contrast, a more rapid disease progression was associated with the VDR-BB genotype. A higher proportion of this genotype was found in patients with <200 CD4 cells/microL (P=.009; odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.7), as well as a faster progression both to AIDS (1993 CDC classification [CDC 1993]) and to a CD4 cell count <200 cells/microL. When the analysis was restricted to patients with a VDR-bb genetic background, patients with CCR5 wtDelta32 heterozygosity were overrepresented in CDC 1993 nonprogressors (P=.033; OR, 0.28; 95% CI, 0.08-0.92) and in those with >200 CD4 cells/microL (P=.062; OR, 0.26; 95% CI, 0.06-1.08). Also, patients with CCR5 wtDelta32 heterozygosity showed a slow progression both to AIDS CDC 1993 and to a CD4 cell count <200 cells/microL.