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15 October 2008

Volume 198, Number 8
The Journal of Infectious Diseases 2008;198:1104–1112
© 2008 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2008/19808-0004$15.00
DOI: 10.1086/591623
MAJOR ARTICLE

Emergence and Persistence of CXCR4‐Tropic HIV‐1 in a Population of Men from the Multicenter AIDS Cohort Study

James C. Shepherd,1,3

Lisa P. Jacobson,2

Wei Qiao,2

Beth D. Jamieson,5

John P. Phair,6,7

Paolo Piazza,8

Thomas C. Quinn,1,4 and

Joseph B. Margolick2

1School of Medicine and 2Bloomberg School of Public Health, Johns Hopkins University, and 3School of Medicine, University of Maryland, Baltimore, and 4National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; 5David Geffen School of Medicine, University of California, Los Angeles; 6Howard Brown Health Center and 7Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and 8Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania

We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV‐1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV‐1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory‐validated, commercially available assay to determine phenotypic coreceptor use. A total of 52% of men had dual‐ or mixed‐tropic HIV‐1 detected at 1 or more of the time points tested. Use of X4 by HIV‐1 was detected more frequently among men who developed AIDS (defined as a CD4+ T cell count of <200 cells/μL and/or an AIDS‐defining illness) 11 years after seroconversion than among those who did not ( ), as well as among men who exhibited a total T cell count decline (i.e., a CD3+ inflection point), compared with those who did not ( ). For men in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4+ T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/μL. We conclude that HIV‐1 variants that used X4 frequently emerged at high CD4+ T cell counts and may contribute to the decrease in T cell numbers during late HIV‐1 infection.

Received 25 September 2007; accepted 16 April 2008; electronically published 10 September 2008.

Reprints or correspondence: Dr. Joseph B. Margolick, Dept. of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Rm. E5153, Baltimore, MD 21205 ().

Cited by

P. Frange, J. Galimand, C. Goujard, C. Deveau, J. Ghosn, C. Rouzioux, L. Meyer, M.-L. Chaix. (2009) High frequency of X4/DM-tropic viruses in PBMC samples from patients with primary HIV-1 subtype-B infection in 1996-2007: the French ANRS CO06 PRIMO Cohort Study. Journal of Antimicrobial Chemotherapy 64:1, 135-141
Online publication date: 1-Aug-2009.
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Holly H. Kim, Eric S. Daar. (2009) Newer antiretroviral agents and how to use them. Current Infectious Disease Reports 11:4, 327-334
Online publication date: 1-Aug-2009.
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Holly H. Kim, Eric S. Daar. (2009) Newer antiretroviral agents and how to use them. Current HIV/AIDS Reports 6:2, 55-62
Online publication date: 1-Jun-2009.
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Matthew Bidwell Goetz, Robert Leduc, Jay R Kostman, Ann M Labriola, Yolanda Lie, Jodi Weidler, Eoin Coakley, Michael Bates, Roberta Luskin-Hawk. (2009) Relationship Between HIV Coreceptor Tropism and Disease Progression in Persons With Untreated Chronic HIV Infection. JAIDS Journal of Acquired Immune Deficiency Syndromes 50:3, 259-266
Online publication date: 1-Apr-2009.
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Harold Burger and Donald Hoover. (2008) HIV‐1 Tropism, Disease Progression, and Clinical Management. The Journal of Infectious Diseases 198:8, 1095-1097
Online publication date: 15-Oct-2008.
Citation-Full Text-PDF Version (48 kB)

  • Potential conflicts of interest: H.M. is an employee of Pfizer. All other authors: none reported.

    Presented in part: XIVth International Conference on AIDS, Toronto, Canada, August 2006 (abstract TUPE0001).

    Financial support: Multicenter AIDS Cohort Study (grants UO1‐AI‐35042, 5‐MO1‐RR‐00722 [GCRC], UO1‐AI‐35043, UO1‐AI‐37984, UO1‐AI‐35039, UO1‐AI‐35040, UO1‐AI‐37613, and UO1‐AI‐35041); Pfizer.

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