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1 September 2007

Volume 45, Number 5
Clinical Infectious Diseases 2007;45:643–649
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4505-0019$15.00
DOI: 10.1086/520650
HIV/AIDS MAJOR ARTICLE

Baseline HIV Type 1 Coreceptor Tropism Predicts Disease Progression

Eric S. Daar,1

Karen L. Kesler,4

Christos J. Petropoulos,2

Wei Huang,2

Michael Bates,2

Alice E. Lail,4

Eoin P. Coakley,2

Edward D. Gomperts,3 and

Sharyne M. Donfield,4

for the Hemophilia Growth and Development Studya

1Los Angeles Biomedical Research Institute at Harbor–University of California–Los Angeles (UCLA) Medical Center and the David Geffen School of Medicine at UCLA, Torrance, 2Monogram Biosciences, South San Francisco, and 3Childrens Hospital Los Angeles, Los Angeles, California; and 4Rho, Chapel Hill, North Carolina

Background.Human immunodeficiency virus type 1 (HIV‐1) coreceptor tropism, the ability of the virus to enter cells via CCR5 or CXCR4, is a viral characteristic mediated by the envelope gene. The impact of coreceptor tropism on the natural history of HIV‐1 infection has not been fully explored.

Methods.Coreceptor tropism was measured using a recombinant virus single‐cycle assay on plasma specimens obtained at baseline from 126 children and adolescents in the Hemophilia Growth and Development Study cohort who were enrolled from 1989 through 1990 and underwent follow‐up through 1997.

Results.Detectable CXCR4‐using virus at baseline was associated with a lower baseline CD4+ T cell count and a higher plasma HIV‐1 RNA level. In addition, it independently predicted a greater decrease in CD4+ T cell count over time ( ) and was associated with a 3.8‐fold increased risk of progression to clinical AIDS.

Conclusions.This study demonstrates that coreceptor tropism, as assessed by this single‐cycle assay, independently influences the natural history of HIV‐1 disease.

Received 11 February 2007; accepted 2 May 2007; electronically published 20 July 2007.

Reprints or correspondence: Dr. Eric S. Daar, 1124 W. Carson St., N‐24, Torrance, CA 90502 ().

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  • Presented in part: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapeutics, Chicago, Illinois, September 2003 (abstract H1722c).

  • Participating centers and individuals are listed at the end of the text.

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