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J Virol. 2009 Sep;83(17):8470-81. doi: 10.1128/JVI.02568-08. Epub 2009 Jun 17.

Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy.

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  • 1Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.


Highly active antiretroviral therapy (HAART) can reduce human immunodeficiency virus type 1 (HIV-1) viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. In addition, 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 use 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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