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 language | English (US) |
|---|---|
| Pages (from-to) | 591-595 |
| Number of pages | 5 |
| Journal | Clinical Infectious Diseases |
| Volume | 44 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 2007 |
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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 journal › Article
}
TY - JOUR
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.
PY - 2007/2/15
Y1 - 2007/2/15
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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U2 - 10.1086/511035
DO - 10.1086/511035
M3 - Article
VL - 44
SP - 591
EP - 595
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 4
ER -