HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor

AIDS Clinical Trial Group A5211

Timothy J. Wilkin, Zhaohui Su, Daniel R. Kuritzkes, Michael Hughes, Charles Williams Flexner, Robert Gross, Eoin Coakley, Wayne Greaves, Catherine Godfrey, Paul R. Skolnik, Joseph Timpone, Benigno Rodriguez, Roy M. Gulick

Research output: Contribution to journalArticle

Abstract

Background. Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors. Methods. We analyzed HIV-infected patients who were screened for participation in Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group protocol A5211, a phase 2b study of the investigational CCR5 inhibitor vicriviroc involving antiretroviral-experienced subjects. Screening CD4+ cell count, HIV-1 plasma RNA level, HIV-1 genotype, and chemokine coreceptor use phenotype were determined. The univariate and multivariate association of subject characteristics with coreceptor use was assessed by logistic regression. Results. Coreceptor use was determined for 391 subjects: 197 (50%) had virus that used the CCR5 coreceptor (the R5 group), 176 (46%) had dual-tropic or mixed HIV-1 populations that used both CCR5 and CXCR4 coreceptors (the D/M group), and 16 (4%) had virus that used the CXCR4 coreceptor (the X4 group). The D/M group had a significantly lower median CD4+ cell count than the R5 virus group (103 cells/μL vs. 170 cells/μL; P <.001). No other characteristics were independently associated. Among 118 subjects who entered A5211 having R5 virus, 12 (10%) had D/M virus according to the results of a second coreceptor test conducted prior to starting treatment with the study drug. Conclusions. Infection with dual-tropic or mixed HIV-1 populations that use both CCR5 and CXCR4 is common among highly treatment-experienced patients, but infection with virus using CXCR4 alone is uncommon. Subjects in the D/M group had significantly lower CD4+ cell counts than subjects in the R5 group. Evaluating coreceptor use will be important in the clinical development of CCR5 and CXCR4 inhibitors.

Original languageEnglish (US)
Pages (from-to)591-595
Number of pages5
JournalClinical Infectious Diseases
Volume44
Issue number4
DOIs
StatePublished - Feb 15 2007

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Chemokines
HIV-1
Acquired Immunodeficiency Syndrome
Clinical Trials
Viruses
CD4 Lymphocyte Count
Virus Diseases
Anti-Retroviral Agents
Clinical Protocols
Natural History
Population
Logistic Models
Genotype
HIV
RNA
Phenotype
Therapeutics
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

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HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor : AIDS Clinical Trial Group A5211. / Wilkin, Timothy J.; Su, Zhaohui; Kuritzkes, Daniel R.; Hughes, Michael; Flexner, Charles Williams; Gross, Robert; Coakley, Eoin; Greaves, Wayne; Godfrey, Catherine; Skolnik, Paul R.; Timpone, Joseph; Rodriguez, Benigno; Gulick, Roy M.

In: Clinical Infectious Diseases, Vol. 44, No. 4, 15.02.2007, p. 591-595.

Research output: Contribution to journalArticle

Wilkin, TJ, Su, Z, Kuritzkes, DR, Hughes, M, Flexner, CW, Gross, R, Coakley, E, Greaves, W, Godfrey, C, Skolnik, PR, Timpone, J, Rodriguez, B & Gulick, RM 2007, 'HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211', Clinical Infectious Diseases, vol. 44, no. 4, pp. 591-595. https://doi.org/10.1086/511035
Wilkin, Timothy J. ; Su, Zhaohui ; Kuritzkes, Daniel R. ; Hughes, Michael ; Flexner, Charles Williams ; Gross, Robert ; Coakley, Eoin ; Greaves, Wayne ; Godfrey, Catherine ; Skolnik, Paul R. ; Timpone, Joseph ; Rodriguez, Benigno ; Gulick, Roy M. / HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor : AIDS Clinical Trial Group A5211. In: Clinical Infectious Diseases. 2007 ; Vol. 44, No. 4. pp. 591-595.
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abstract = "Background. Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors. Methods. We analyzed HIV-infected patients who were screened for participation in Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group protocol A5211, a phase 2b study of the investigational CCR5 inhibitor vicriviroc involving antiretroviral-experienced subjects. Screening CD4+ cell count, HIV-1 plasma RNA level, HIV-1 genotype, and chemokine coreceptor use phenotype were determined. The univariate and multivariate association of subject characteristics with coreceptor use was assessed by logistic regression. Results. Coreceptor use was determined for 391 subjects: 197 (50{\%}) had virus that used the CCR5 coreceptor (the R5 group), 176 (46{\%}) had dual-tropic or mixed HIV-1 populations that used both CCR5 and CXCR4 coreceptors (the D/M group), and 16 (4{\%}) had virus that used the CXCR4 coreceptor (the X4 group). The D/M group had a significantly lower median CD4+ cell count than the R5 virus group (103 cells/μL vs. 170 cells/μL; P <.001). No other characteristics were independently associated. Among 118 subjects who entered A5211 having R5 virus, 12 (10{\%}) had D/M virus according to the results of a second coreceptor test conducted prior to starting treatment with the study drug. Conclusions. Infection with dual-tropic or mixed HIV-1 populations that use both CCR5 and CXCR4 is common among highly treatment-experienced patients, but infection with virus using CXCR4 alone is uncommon. Subjects in the D/M group had significantly lower CD4+ cell counts than subjects in the R5 group. Evaluating coreceptor use will be important in the clinical development of CCR5 and CXCR4 inhibitors.",
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T1 - HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor

T2 - AIDS Clinical Trial Group A5211

AU - Wilkin, Timothy J.

AU - Su, Zhaohui

AU - Kuritzkes, Daniel R.

AU - Hughes, Michael

AU - Flexner, Charles Williams

AU - Gross, Robert

AU - Coakley, Eoin

AU - Greaves, Wayne

AU - Godfrey, Catherine

AU - Skolnik, Paul R.

AU - Timpone, Joseph

AU - Rodriguez, Benigno

AU - Gulick, Roy M.

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N2 - Background. Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors. Methods. We analyzed HIV-infected patients who were screened for participation in Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group protocol A5211, a phase 2b study of the investigational CCR5 inhibitor vicriviroc involving antiretroviral-experienced subjects. Screening CD4+ cell count, HIV-1 plasma RNA level, HIV-1 genotype, and chemokine coreceptor use phenotype were determined. The univariate and multivariate association of subject characteristics with coreceptor use was assessed by logistic regression. Results. Coreceptor use was determined for 391 subjects: 197 (50%) had virus that used the CCR5 coreceptor (the R5 group), 176 (46%) had dual-tropic or mixed HIV-1 populations that used both CCR5 and CXCR4 coreceptors (the D/M group), and 16 (4%) had virus that used the CXCR4 coreceptor (the X4 group). The D/M group had a significantly lower median CD4+ cell count than the R5 virus group (103 cells/μL vs. 170 cells/μL; P <.001). No other characteristics were independently associated. Among 118 subjects who entered A5211 having R5 virus, 12 (10%) had D/M virus according to the results of a second coreceptor test conducted prior to starting treatment with the study drug. Conclusions. Infection with dual-tropic or mixed HIV-1 populations that use both CCR5 and CXCR4 is common among highly treatment-experienced patients, but infection with virus using CXCR4 alone is uncommon. Subjects in the D/M group had significantly lower CD4+ cell counts than subjects in the R5 group. Evaluating coreceptor use will be important in the clinical development of CCR5 and CXCR4 inhibitors.

AB - Background. Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors. Methods. We analyzed HIV-infected patients who were screened for participation in Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group protocol A5211, a phase 2b study of the investigational CCR5 inhibitor vicriviroc involving antiretroviral-experienced subjects. Screening CD4+ cell count, HIV-1 plasma RNA level, HIV-1 genotype, and chemokine coreceptor use phenotype were determined. The univariate and multivariate association of subject characteristics with coreceptor use was assessed by logistic regression. Results. Coreceptor use was determined for 391 subjects: 197 (50%) had virus that used the CCR5 coreceptor (the R5 group), 176 (46%) had dual-tropic or mixed HIV-1 populations that used both CCR5 and CXCR4 coreceptors (the D/M group), and 16 (4%) had virus that used the CXCR4 coreceptor (the X4 group). The D/M group had a significantly lower median CD4+ cell count than the R5 virus group (103 cells/μL vs. 170 cells/μL; P <.001). No other characteristics were independently associated. Among 118 subjects who entered A5211 having R5 virus, 12 (10%) had D/M virus according to the results of a second coreceptor test conducted prior to starting treatment with the study drug. Conclusions. Infection with dual-tropic or mixed HIV-1 populations that use both CCR5 and CXCR4 is common among highly treatment-experienced patients, but infection with virus using CXCR4 alone is uncommon. Subjects in the D/M group had significantly lower CD4+ cell counts than subjects in the R5 group. Evaluating coreceptor use will be important in the clinical development of CCR5 and CXCR4 inhibitors.

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