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

Janet L. Lathey; Camlin Tierney; Sheng Yung P. Chang; Richard T. D’aquila; Daniel M. Bettendorf; Heather C. Alexander; Christopher D. Santini; Angela M. Hughes; Charlene F. Barroga; Stephen A. Spector; Jeff E. Landes; Scott M. Hammer; David A. Katzenstein; S. Hammer; J. Lathey; S. Fiscus; B. Jackson; H. Farzadegan; S. Rasheed; T. Elbeik; R. Reichman; A. Japour; R. D’aquila; W. Scott; B. Griffith; AIDS Clinical Trials Group 175 Virology Team

doi:10.1086/324427

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

Janet L. Lathey, Camlin Tierney, Sheng Yung P. Chang, Richard T. D’aquila, Daniel M. Bettendorf, Heather C. Alexander, Christopher D. Santini, Angela M. Hughes, Charlene F. Barroga, Stephen A. Spector, Jeff E. Landes, Scott M. Hammer, David A. Katzenstein, S. Hammer, J. Lathey, S. Fiscus, B. Jackson, H. Farzadegan, S. Rasheed, T. ElbeikR. Reichman, A. Japour, R. D’aquila, W. Scott, B. Griffith, AIDS Clinical Trials Group 175 Virology Team

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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.

Original language	English (US)
Pages (from-to)	1402-1411
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	184
Issue number	11
DOIs	https://doi.org/10.1086/324427
State	Published - Dec 2001

Bibliographical note

Funding 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 (jlathey@zycos.com).

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Lathey, J. L., Tierney, C., Chang, S. Y. P., D’aquila, R. T., Bettendorf, D. M., Alexander, H. C., Santini, C. D., Hughes, A. M., Barroga, C. F., Spector, S. A., Landes, J. E., Hammer, S. M., Katzenstein, D. A., Hammer, S., Lathey, J., Fiscus, S., Jackson, B., Farzadegan, H., Rasheed, S., ... AIDS Clinical Trials Group 175 Virology Team (2001). Associations of CCR5 CCR2 and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy. Journal of Infectious Diseases, 184(11), 1402-1411. https://doi.org/10.1086/324427

Associations of CCR5 CCR2 and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy. / Lathey, Janet L.; Tierney, Camlin; Chang, Sheng Yung P. et al.
In: Journal of Infectious Diseases, Vol. 184, No. 11, 12.2001, p. 1402-1411.

Research output: Contribution to journal › Article › peer-review

Lathey, JL, Tierney, C, Chang, SYP, D’aquila, RT, Bettendorf, DM, Alexander, HC, Santini, CD, Hughes, AM, Barroga, CF, Spector, SA, Landes, JE, Hammer, SM, Katzenstein, DA, Hammer, S, Lathey, J, Fiscus, S, Jackson, B, Farzadegan, H, Rasheed, S, Elbeik, T, Reichman, R, Japour, A, D’aquila, R, Scott, W, Griffith, B & AIDS Clinical Trials Group 175 Virology Team 2001, 'Associations of CCR5 CCR2 and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy', Journal of Infectious Diseases, vol. 184, no. 11, pp. 1402-1411. https://doi.org/10.1086/324427

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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.",

author = "Lathey, {Janet L.} and Camlin Tierney and Chang, {Sheng Yung P.} and D{\textquoteright}aquila, {Richard T.} and Bettendorf, {Daniel M.} and Alexander, {Heather C.} and Santini, {Christopher D.} and Hughes, {Angela M.} and Barroga, {Charlene F.} and Spector, {Stephen A.} and Landes, {Jeff E.} and Hammer, {Scott M.} and Katzenstein, {David A.} and S. Hammer and J. Lathey and S. Fiscus and B. Jackson and H. Farzadegan and S. Rasheed and T. Elbeik and R. Reichman and A. Japour and R. D{\textquoteright}aquila and W. Scott and B. Griffith and {AIDS Clinical Trials Group 175 Virology Team}",

note = "Funding 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 (jlathey@zycos.com).",

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AU - D’aquila, Richard T.

AU - Bettendorf, Daniel M.

AU - Alexander, Heather C.

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AU - Jackson, B.

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AU - Rasheed, S.

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AU - Reichman, R.

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AU - Griffith, B.

AU - AIDS Clinical Trials Group 175 Virology Team

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

Abstract

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