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 …

TP Brennan, JO Woods, AR Sedaghat… - Journal of …, 2009 - Am Soc Microbiol
Journal of virology, 2009Am Soc Microbiol
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 …
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.
American Society for Microbiology