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

TitlePlasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection.
Publication TypeJournal Article
Year of Publication2009
AuthorsJiang W, Lederman MM, Hunt P, Sieg SF, Haley K, Rodriguez B, Landay A, Martin J, Sinclair E, Asher AI, Deeks SG, Douek DC, Brenchley JM
JournalJ Infect Dis
Volume199
Issue8
Pagination1177-85
Date Published2009 Apr 15
ISSN0022-1899
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Case-Control Studies, CD4-Positive T-Lymphocytes, Cohort Studies, DNA, Bacterial, DNA, Ribosomal, HIV Infections, Humans, Lipopolysaccharides, Middle Aged, Polymerase Chain Reaction, RNA, Bacterial, RNA, Ribosomal, 16S, Viral Load, Young Adult
Abstract

The significance of elevated plasma levels of bacterial lipopolysaccharide (LPS) in persons with chronic HIV infection remains undefined. We measured LPS levels by use of limulus lysate assay, and DNA sequences 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 16S rDNA during 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.

DOI10.1086/597476
Alternate JournalJ. Infect. Dis.
PubMed ID19265479
PubMed Central IDPMC2728622
Grant ListAI 076174 / AI / NIAID NIH HHS / United States
AI 25879 / AI / NIAID NIH HHS / United States
AI 36219 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI055273 / AI / NIAID NIH HHS / United States
AI44595 / AI / NIAID NIH HHS / United States
P01 AI076174 / AI / NIAID NIH HHS / United States
P01 AI076174-01A10001 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
P30 AI036219-149005 / AI / NIAID NIH HHS / United States
P30 AI27763 / AI / NIAID NIH HHS / United States
P30 MH59037 / MH / NIMH NIH HHS / United States
P30 MH62246 / MH / NIMH NIH HHS / United States
U01 AI025879 / AI / NIAID NIH HHS / United States
U01 AI025879-100004 / AI / NIAID NIH HHS / United States
U01 AI025879-119001 / AI / NIAID NIH HHS / United States
U01 AI025879-120004 / AI / NIAID NIH HHS / United States
U01 AI025879-160004 / AI / NIAID NIH HHS / United States
U01 AI025879-169001 / AI / NIAID NIH HHS / United States
UL1 RR024131-01 / RR / NCRR NIH HHS / United States
Z99 AI999999 / / Intramural NIH HHS / United States