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

Abstract

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.