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.

Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Journal of Virology (Impact Factor: 4.65). 07/2009; 83(17):8470-81. DOI: 10.1128/JVI.02568-08
Source: PubMed

ABSTRACT 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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