Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection

Wei Jiang, Michael M. Lederman, Peter Hunt, Cott F. Sieg, Kathryn Haley, Benigno Rodriguez, Alan Landay, Jeffrey Martin, Elizabeth Sinclair, Ava I. Asher, Steven G. Deeks, Daniel C. Douek, Jason M. Brenchley

Research output: Contribution to journalArticlepeer-review

497 Scopus citations

Abstract

The significance of elevated plasma levels of bacterial lipopolysaccharide (LPS) in persons with chronic HIV infection remains undefined.Wemeasured LPS levels by use of limulus lysate assay, andDNAsequences encoding bacterial ribosomal 16S RNA (16S rDNA) were assessed by quantitative polymerase chain reactions in plasma samples obtained from 242 donors. Plasma levels of 16S rDNA were significantly higher in human immunodeficiency virus (HIV)-infected subjects than in uninfected subjects, and they correlated with LPS levels. Higher levels of 16S rDNA were associated with higher levels of T cell activation and with lower levels of CD4 T cell restoration during antiretroviral therapy. Antiretroviral therapy reduces but does not fully normalize plasma levels of bacterial 16S rDNA, an index of microbial translocation from the gastrointestinal tract. High levels of 16SrDNAduring therapy are strongly associated with reduced increases in the CD4 + T lymphocyte count, irrespective of plasma HIV RNA levels. These findings are consistent with the importance of microbial translocation in immunodeficiency and T cell homeostasis in chronic HIV infection.

Original languageEnglish (US)
Pages (from-to)1177-1185
Number of pages9
JournalJournal of Infectious Diseases
Volume199
Issue number8
DOIs
StatePublished - Apr 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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