Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the "Probio-HIV" Clinical Trial

Abstract

Background: HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation.

Methods: In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma.

Results: We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls.

Conclusions: Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis.

Trial registration: ClinicalTrials.gov NCT02164344.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. The CONSORT flow diagram of the clinical trial.

Experimental design of the study.

Fig 2. Immune activation on T-lymphocytes.

Longitudinal assessment of activation markers(CD38+HLA-DR+) on CD4+ cells (A) and on CD8+cells (B)before (T0) and after (T1) probiotic diet supplementation. Control group was added for comparison. Horizontal bars in the scatter plot represent mean value with SD. P values

Fig 3. Plasma levels of sCD14, d-dimer and LBP.

Scatter plots of sCD14 (A), d-dimer (B) and Lipopolysaccharide Binding Protein (LBP)(C) in patients before (T0) and after probiotics’ intake (T1) compared with controls. Horizontal bars in the scatter plot represent mean value with SD. P values

Fig 4. HsCRP plasma levels.

High-sensitivity C-reactive protein (hsCRP) distribution in patients before (T0), and after probiotics’ assumption (T1) compared with controls Horizontal bars in the scatter plot represent mean value with SD. P values

Fig 5. Levels of immune activation according to the age on CD4+ T-cells.

Extent of expression and co-expression of activation markers CD38 and HLA-DR on CD4+ T-lymphocytes before (T0) and after probiotics’ intake (T1) in patients with less (A) and more (B) than 55 years. Horizontal bars in the scatter plot represent mean value with SD. P values

Fig 6. Effects of probiotics on T-cells activation in patients with CD4 count less than 250 cells/μl.

Longitudinal assessment of CD38 and HLA-DR markers and their simultaneous expression on CD4 T cells in peripheral blood. in patients with a CD4 count less than 250 cells/μl at HIV infection diagnosis. P values

Fig 7. IL-6, nadir and immune activation at baseline.

IL-6 levels at T0 were inversely correlated to CD4-Nadir (A) and CD4% (B), and positively correlated with the frequencies of activated, CD4+CD38+ T-cells (C). P values