JVI Accepts, published online ahead of print on 17 June 2009

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J. Virol. doi:10.1128/JVI.02568-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of HIV-1 Viremia and Provirus in Resting CD4⁺ T Cells Reveals a Novel Source of Residual Viremia in Patients on Antiretroviral Therapy

Timothy P. Brennan, John O. Woods, Ahmad R. Sedaghat, Janet D. Siliciano, Robert F. Siliciano, and Claus O. Wilke^*

Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Institute for Cell and Molecular Biology, The University of Texas at Austin, Austin, TX 78712; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Howard Hughes Medical Institute, Baltimore, MD 21205; Center for Computational Biology and Bioinformatics and Section of Integrative Biology, The University of Texas at Austin, Austin, TX 78712

^* To whom correspondence should be addressed. Email: cwilke{at}mail.utexas.edu.

Highly active antiretroviral therapy (HAART) can reduce HIV-1 viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. Additionally, a long-lived latent reservoir for HIV-1 exists in resting memory CD4⁺ T cells. This reservoir is believed to be a source of the residual viremia and is the focus of eradication efforts. Here, we employ two measures of population structure, analysis of molecular variance and the Slatkin-Maddison test, to demonstrate that the residual viremia is genetically distinct from proviruses in resting CD4⁺ T cells, but that proviruses in resting and activated CD4⁺ T cells belong to a single population. Residual viremia is genetically distinct from proviruses in activated CD4⁺ T cells, monocytes, and unfractionated peripheral blood mononuclear cells. The finding that some of the residual viremia in patients on HAART stems from an unidentified cellular source other than CD4⁺ T cells has implications for eradication efforts.

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