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.
Bibliographical noteFunding Information:
Received 21 November 2000; revised 7 August 2001; electronically published 13 November 2001. Presented in part: 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, January 2000 (abstract 853). Informed consent was obtained from all study participants. The study followed the human experimentation guidelines of the US Department of Health and Human Services. Financial support: National Institutes of Health (AI-27670 to J.L.L.; AI-38855 to C.T. and D.M.B.; AI2-7659 and AI-29193 to R.T.D.; AI-139004 and AI-36214 to S.A.S.). aPresent affiliations: ZYCOS, Lexington, Massachusetts (J.L.L.); Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee (R.T.D.). b Study team members are listed after the text. Reprints or correspondence: Dr. Janet L. Lathey, Clinical Assay, ZYCOS, 44 Hartwell Ave., Lexington, MA 02421 (email@example.com).