Table 2.
Overview of studies suggesting that microbial translocation through the gastrointestinal tract is a cause of immune activation and immune dysfunction in HIV/SIV infectionsa
| Reference | Study design | Study population(s) | Main findings |
|---|---|---|---|
| 33 | Cross-sectional | HIV-infected patients | Higher levels of LPS in HIV-infected patients |
| SIV-infected rhesus macaques | LPS level increases following SIV infection in RM | ||
| Positive correlation between plasma LPS levels and circulating CD8+ CD38+ HLA-DR+ T cells | |||
| Inverse correlation between plasma LPS levels and TNF+ IL-1+ monocytes upon LPS stimulation | |||
| Inverse correlation between plasma LPS levels and plasma EndoCAb titers | |||
| 39 | Cross-sectional | INRs on HAART | Higher LPS levels in INRs and advanced naïve patients |
| Full-responder patients on HAART | Positive correlation between LPS and proliferating Ki67+ CD8+ T cells in INRs | ||
| Advanced naïve patients | Higher plasma enterobacterial DNA levels in INRs | ||
| 45 | Cross-sectional and longitudinal | Case Western Reserve University Cohort, with (i) HIV-negative patients, (ii) HIV-positive naïve patients, (iii) HIV-positive treated patients with undetectable viremia, and (iv) HIV-positive treated patients with detectable viremia | Increased bacterial 16S rRNA levels in HIV-infected patients |
| UCSF SCOPE Cohort | Correlation of bacterial 16S rRNA with LPS in HAART-treated patients | ||
| ACTG study 5014 | Correlation of 16S rRNA levels (i) directly with the frequency of CD38+ and HLA-DR+ CD8+ T cells and (ii) inversely with the degree of CD4+ restoration on HAART | ||
| Decrease in 16S rRNA levels following HAART | |||
| 59 | Cross-sectional | HIV-infected patients, HAART naïve | Correlation between Ki67-expressing T cells in the gut and plasma LPS levels |
| HIV-infected patients on HAART | |||
| HIV-negative controls | |||
| 60 | Cross-sectional | HIV-1-infected patients, HAART naïve | Higher LPS levels in patients with AIDS than in controls |
| HIV-1-infected patients with AIDS | Correlation between LPS levels, CD4+ T-cell lymphopenia, and HIV RNA load | ||
| HIV-2-infected patients, HAART naïve | Inverse correlation between plasma LPS levels and expression of IL-12 and IFN-α following TLR stimulation | ||
| HIV-2-infected patients with AIDS | No difference between HIV-1- and HIV-2-infected individuals within the same disease stage, CD4+ T-cell count, or viral load intervals | ||
| HIV-negative controls | |||
| 61 | Cross-sectional | SIV-uninfected pigtail macaques | Increased plasma LPS levels and intestinal permeability in uninfected pigtail macaques |
| SIV-uninfected rhesus macaques | Tight-epithelial-barrier damage and increased lamina propria LPS levels in uninfected pigtail macaques | ||
| HIV-negative controls | Correlation between breaches in the colon, microbial translocation, and local immune activation | ||
| Microbial translocation and immune activation in the colon result in systemic microbial translocation and immune activation | |||
| 62 | Cross-sectional | HIV-infected patients, HAART naïve | Decrease in activated CD14+ CD16+ monocytes, correlating with HIV RNA, in course of HAART |
| HIV-infected patients on HAART | Elevated sCD14 and TNF-α levels persist in course of HAART | ||
| HIV-negative controls | |||
| 63 | Cross-sectional | SIV-uninfected sooty mangabeys | Highest LPS levels in lamina propria of chronically infected/AIDS animals |
| SIV-infected sooty mangabeys | Damage of epithelial barrier associated with infiltration of microbial products into the lamina propria | ||
| SIV-uninfected rhesus macaques | Correlation between damage of the epithelial barrier and microbial translocation (highest in chronically infected/AIDS animals) | ||
| SIV-infected rhesus macaques | |||
| 40 | Longitudinal | HIV-infected patients starting HAART with CD4+ counts of <200 cells/μl | Persistence of high LPS and sCD14 levels despite suppressive HAART |
| Lack of probiotic Lactobacillaceae DNA in plasma both prior and after therapy in patients with CD4+ counts of <200 cells/μl following HAART | |||
| 64 | Cross-sectional | HIV-infected patients, HAART naïve | Negative correlation between total bacterial load and duodenal activated CD4+ and CD8+ T cells |
| HIV-infected patients on HAART | Positive correlation between fecal Bacteroidales (rRNA) and activated, peripheral CD8+ T cells | ||
| HIV-negative controls | Negative correlation between fecal Enterobacteriales (rRNA) and duodenal CD4+ T cells | ||
| 65 | Cross-sectional | HIV-infected patients, HAART naïve | Correlation between gut HIV DNA, plasma LPS, and peripheral CD8+ CD38+ T cells in HAART-treated patients |
| HIV-infected patients on HAART | |||
| HIV-negative controls | |||
| 66 | Cross-sectional | HIV-infected patients, HAART naïve | Depletion of gut Th17 cells, which is normalized by HAART |
| HIV-infected patients on HAART | Persistence of high LPS levels despite HAART | ||
| HIV-negative controls | Inverse correlation was observed between plasma LPS levels and gut Th17 frequencies | ||
| Correlation between plasma LPS levels and gut HIV proviral reservoir | |||
| 38 | Cross-sectional | HIV-infected patients on HAART | Positive correlation between LPS and sCD14 and gut-homing CD4+ T cells in the blood |
| HIV-negative controls | Inverse correlation between LPS and sCD14 and gut-homing CD4+ T cells in the gut | ||
| Positive correlation between peripheral CD4+ Ki67+ cells and circulating gut-homing CD4+ T cells |
a
Studies are listed in chronological order.