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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)8470-8481
Number of pages12
JournalJournal of virology
Volume83
Issue number17
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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