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Journal of Virology, October 2004, p. 11296-11302, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11296-11302.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Evolution of Human Immunodeficiency Virus Type 1 Coreceptor Usage during Antiretroviral Therapy: a Bayesian Approach

Christina M. R. Kitchen,1* Sean Philpott,2 Harold Burger,2 Barbara Weiser,2 Kathryn Anastos,3 and Marc A. Suchard4

Department of Biostatistics, UCLA School of Public Health,1 Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California,4 Wadsworth Center, New York State Department of Health, Albany,2 Montefiore Medical Center, Bronx, New York3

Received 25 February 2004/ Accepted 8 June 2004

There is substantial evidence for ongoing replication and evolution of human immunodeficiency virus type 1 (HIV-1), even in individuals receiving highly active antiretroviral therapy. Viral evolution in the presence of antiviral therapy needs to be considered when developing new therapeutic strategies. Phylogenetic analyses of HIV-1 sequences can be used for this purpose but may give rise to misleading results if rates of intrapatient evolution differ significantly. To improve analyses of HIV-1 evolution relevant to studies of pathogenesis and treatment, we developed a Bayesian hierarchical model that incorporates all available sequence data while simultaneously allowing the phylogenetic parameters of each patient to vary. We used this method to examine evolutionary changes in HIV-1 coreceptor usage in response to treatment. We examined patients whose viral populations exhibited a shift in coreceptor utilization in response to therapy. CXCR4 (X4) strains emerged in each patient but were suppressed following initiation of new antiretroviral regimens, so that CCR5-utilizing (R5) strains predominated. By phylogenetically reconstructing the evolutionary relationship of HIV-1 obtained longitudinally from each patient, it was possible to examine the origin of the reemergent R5 virus. Using our Bayesian hierarchical approach, we found that the reemergent R5 virus detectable after therapy was more closely related to the predecessor R5 virus than to the X4 strains. The Bayesian hierarchical approach, unlike more traditional methods, makes it possible to evaluate competing hypotheses across patients. This model is not limited to analyses of HIV-1 but can be used to elucidate evolutionary processes for other organisms as well.

* Corresponding author. Mailing address: Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA 90095-1772. Phone: (310) 267-2113. Fax: (310) 267-2113. E-mail: cr{at}ucla.edu.

Journal of Virology, October 2004, p. 11296-11302, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11296-11302.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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