Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection.
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.
Jiang
Wei
W
Case Western Reserve University, Cleveland, Ohio 44106, USA.
Lederman
Michael M
MM
Hunt
Peter
P
Sieg
Scott F
SF
Haley
Kathryn
K
Rodriguez
Benigno
B
Landay
Alan
A
Martin
Jeffrey
J
Sinclair
Elizabeth
E
Asher
Ava I
AI
Deeks
Steven G
SG
Douek
Daniel C
DC
Brenchley
Jason M
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016022:Case-Control Studies; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000097:blood*; D004275:DNA, Ribosomal / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D008070:Lipopolysaccharides; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S