HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Academic Article uri icon



  • 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), 178 [corrected] (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/ micro L vs. 170 cells/ mu L; 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.


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

publication date

  • January 17, 2007



  • Acquired Immunodeficiency Syndrome
  • Anti-Retroviral Agents
  • HIV-1
  • Receptors, CCR5
  • Receptors, CXCR4


Scopus Document Identifier

  • 33846932573

PubMed ID

  • 17243065

Additional Document Info


  • 44


  • 4