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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.

Interleukin-17 (IL-17) is a pro-inflammatory cytokine that is mainly produced by CD4+ T cells. The role of Th17 during the human immunodeficiency virus (HIV)-1 infection is still unclear, but HIV-1 infection can cause a preferential depletion of Th17 cells. It has been shown that IL-15 elicits IL-17 production from human peripheral blood mononuclear cells. We studied the effect of IL-15 stimulation in vitro on IL-17 production from CD4+ mononuclear cells of HIV-infected patients. We observed that IL-15 triggers, in a dose-dependent manner, IL-17 secretion. This effect was blocked by anti-IL-15 monoclonal antibody (P=0.01). Interestingly, IL-17 production was significantly lower in patients with detectable plasma viremia when compared with successfully treated HIV-infected patients (P=0.02) and healthy controls, respectively (P<0.001). We also noticed a significant difference in IL-17 production between naïve HIV-infected patients and patients with virological failure on combined antiretroviral therapy (cART) (P=0.02). Our results suggest that IL-15 can induce IL-17 production from peripheral CD4+ mononuclear cells of HIV-infected patients. Persistent HIV plasma viremia could cause a severe perturbation of IL-17 production from CD4+ mononuclear cells. IL-17 production in HIV-infected patients could be recovered through a sustained suppression of the viral replication in the peripheral blood through cART.