Bacterial translocation of LPS is associated with lower cognitive abilities in men living with HIV receiving antiretroviral therapy


BACKGROUND: Gut protective CD4 T-helper producing interleukin 17 (Th17), are preferential target of HIV and are rapidly depleted upon infection. Such depletion persists under antiretroviral therapy (ART) in people living with HIV (PLWH). This gut damage allows bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) microbial translocation contributing to systemic inflammation and risk of non-AIDS comorbidities, including neurocognitive diseases. Herein, we assessed whether 1) markers of gut damage like intestinal fatty acid-binding protein (I-FABP) and regenerating islet-derived protein 3a (REG3a) and 2) microbial translocation markers, LPS and BDG were associated with cognitive function in ART-treated PLWH.
METHODS: A total of 80 ART-treated men living with HIV from the Brain Health Now Canadian cohort was included. Detailed socio-demographic and clinical characteristics were collected for all participants. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups of 26-27 participants were selected based on their B-CAM levels: low (<19), intermediate (19-26) or high (>26). We excluded participants who received antibiotics or proton pump inhibitors or antiacids which modify microbial translocation, in the past 3 months. Cannabis users were also excluded. Plasma levels of I-FABP, REG3a, and LPS were quantified by ELISA, while BDG levels were assessed using the Fungitell assay.
RESULTS: Plasma levels of I-FABP, REG3a, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3a levels were higher in participants with PDQ higher than the median of 26.5, indicating that those with lowest self-reported cognitive function had higher levels of those markers (p=0.01 and 0.004 respectively).
Multivariable analyses showed that LPS association with PDQ was independent of age and level of education. However, similar analyses showed no significant association between LPS levels and B-CAM levels. I-FABP, REG3a and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses.
CONCLUSIONS: In this well characterized prospective cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with lowest self-reported cognitive function. The mechanism behind such association should be explored in interventional studies.

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