Abstract
Immunologic non-responders (INRs) are a subset of individuals living with HIV who have suboptimal blood CD4+ T cell recovery despite effective antiretroviral therapy (ART). They are at an increased risk of serious non-AIDS co-morbidities and death, and demonstrate enhanced systemic immune activation. In other populations diet has been correlated with markers of systemic inflammation through the Diet Inflammatory Index (DII), but this association has not been studied in persons living with HIV (PLWH). Blood was collected from 28 INR PLWH with a blood CD4+ T cell count <350/μL despite ≥2 years of effective ART. Participants completed a Canadian Diet History Questionnaire, and their responses were used to calculate the DII. Plasma inflammatory markers (IFNγ, TNF, IL-6, sVCAM, D-dimer, sCD14 and CRP) were assayed by ELISA, cellular immune activation (HLA-DR and CD38 on CD4+ and CD8+ T cells) was quantified using flow cytometry, and small bowel permeability assessed by calculation of the urine LacMan ratio after drinking a mix of lactulose and mannitol. Participants were a median age of 57 years, had been on effective ART for 15 years, and the median DII was −1.91 (range of −3.78 to +2.23). No correlation was observed between DII and plasma markers of inflammation, levels of T cell activation, gut permeability, or the biomarker of bacterial translocation sCD14. Self-reported alcohol intake, a potential confounder of the relationship between diet and inflammatory biomarkers, was also not associated with systemic inflammation or gut permeability. Our findings suggest that other mechanisms, rather than diet, are likely to be the major driver of systemic inflammation in INR individuals.
Highlights
Effective viral suppression by antiretroviral therapy (ART) among people living with HIV dramatically increases life expectancy and limits disease progression to AIDS [1]
Immunologic non-response is commonly defined by a failure to restore normal CD4+ T cell counts in blood despite virus suppression on ART, and Immunologic non-responders (INRs) individuals are at a high risk of serious non-AIDS co-morbidities and mortality [9,10,11]
INR demonstrate elevated biomarkers of plasma and blood T cell activation when compared to general population, as well as to persons living with HIV (PLWH) who have normalized their blood CD4+ T cell count on ART [8]
Summary
Effective viral suppression by antiretroviral therapy (ART) among people living with HIV dramatically increases life expectancy and limits disease progression to AIDS [1]. CD8+ T cell activation is enhanced in INR individuals compared to clinical responders (CRs) who achieve a higher blood CD4+ T cell count during ART [8], and while the INR phenotype is incompletely understood this chronic immune activation may be why these individuals are at a higher risk of serious non-AIDS co-morbidities and mortality [9,10,11]. While mechanisms are insufficiently defined, diet composition reproducibly affects the gut microbiota and influences microbial translocation [17, 24,25,26] The latter activates innate immune cells, including monocytes [27, 28], in part through the interaction of CD14 with bacterial lipopolysaccharide (LPS), LPS binding protein (LPB) and/or the MD-2/Toll-like receptor 4 (TLR4) signaling; this leads to the release of soluble CD14 (sCD14), which is measurable in blood plasma [27]. The DII uses diet information to measure the inflammatory potential of diet [30,31,32,33], and we hypothesized that an elevated DII score (indicating a more pro-inflammatory diet) would be associated with increased plasma markers of inflammation and T cell activation in PLWH who were of the INR phenotype
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