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15 February 2007

Volume 44, Number 4
Clinical Infectious Diseases 2007;44:591–595
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4404-0019$15.00
DOI: 10.1086/511035
HIV/AIDS MAJOR ARTICLE

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,1

Zhaohui Su,2

Daniel R. Kuritzkes,3

Michael Hughes,2

Charles Flexner,5

Robert Gross,7

Eoin Coakley,8

Wayne Greaves,9

Catherine Godfrey,6

Paul R. Skolnik,4

Joseph Timpone,10

Benigno Rodriguez,11 and

Roy M. Gulick1

1Division of International Medicine and Infectious Diseases, Weill‐Cornell Medical College, New York, New York; 2Department of Biostatistics, Harvard School of Public Health, 3Section of Retroviral Therapeutics, Brigham and Women’s Hospital and Division of AIDS, Harvard Medical School, and 4Center for HIV/AIDS Care and Research, Boston University School of Medicine, Boston, Massachusetts; 5Pharmacology and Molecular Sciences and International Health, Johns Hopkins University, Baltimore, and 6Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 7Center for Clinical Epidemiology and Biostatistics and Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; 8Monogram Biosciences, South San Francisco, California; 9Schering‐Plough Research Institute, Kenilworth, New Jersey; 10Division of Infectious Diseases, Georgetown University School of Medicine, Washington, D.C.; and 11Division of Infectious Diseases, University Hospital of Cleveland, Ohio

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; ). 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.

Received 28 June 2006; accepted 19 October 2006; electronically published 17 January 2007.

  • (See the editorial commentary by Melby on pages 596–8)

Reprints or correspondence: Dr. Timothy Wilkin, 119 W. 24th St., Ground Fl., New York, NY 10011 ().

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  • Presented in part: 2006 Conference on Retroviruses and Opportunistic Infections, Denver, Colorado, February 2006 (abstract 665).

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