Inflammation In HIV Patients Research Articles

Short Communication: Paraoxonase 1 (PON1) in French HIV-Infected Patients Under Antiretroviral Therapy: Relationship with the Metabolic Syndrome and Inflammation

Our goal was to determine if paraoxonase 1 (PON1) activity relates to the presence of metabolic syndrome (MS) and inflammation in HIV patients treated with highly active antiretroviral therapy (HAART). This was a prospective, multicenter study including 269 patients receiving HAART for at least 1 year and a maximum of 4 years. PON1 and inflammatory markers [C reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA), and soluble tumor necrosis factor receptors 2 (sTNF-R2)] were compared between patients with or without MS and the association between inflammatory markers and PON1 was assessed by logistic regression analyses. MS was found in 18.2% of the patients. Inflammatory markers, with the exception of sTNF-R2, were significantly higher, while PON1 activity was significantly lower in the presence of metabolic syndrome. PON1 activity was significantly related to apolipoprotein C3, CD4 count, and sTNF-R2. It may be concluded that PON1 appears to be a marker for the metabolic syndrome in HIV-infected subjects. PON1 activity is related to dyslipidemia and the immunological status of the patients but is not fully determined by inflammation.

Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation

FcRγ is an ITAM-containing adaptor required for CD16 signaling and function in NK cells. We have previously shown that NK cells from HIV patients receiving combination antiretroviral therapy (cART) have decreased FcRγ expression, but the factors causing this are unknown. We conducted a cross-sectional study of cART-naive viremic patients (ART(-)), virologically suppressed patients receiving cART (ART(+)), and HIV-uninfected controls. CD8(+) T cells were activated, as assessed by CD38(+)HLA-DR(+) expression, in ART(-) patients (p < 0.0001), which was significantly reduced in ART(+) patients (p = 0.0005). In contrast, CD38(+)HLA-DR(+) NK cells were elevated in ART(-) patients (p = 0.0001) but did not decrease in ART(+) patients (p = 0.88). NK cells from both ART(-) and ART(+) patients showed high levels of spontaneous degranulation in ex vivo whole blood assays as well as decreased CD16 expression (p = 0.0001 and p = 0.0025, respectively), FcRγ mRNA (p < 0.0001 for both groups), FcRγ protein expression (p = 0.0016 and p < 0.0001, respectively), and CD16-dependent Syk phosphorylation (p = 0.0001 and p = 0.003, respectively). HIV-infected subjects showed alterations in NK activation, degranulation, CD16 expression and signaling, and elevated plasma markers of inflammation and macrophage activation, that is, neopterin and sCD14, which remained elevated in ART(+) patients. Alterations in NK cell measures did not correlate with viral load or CD4 counts. These data show that in HIV patients who achieve viral suppression following cART, NK cell activation persists. This suggests that NK cells respond to factors different from those driving T cell activation, but which are associated with inflammation in HIV patients.

Increased small intestinal and colonic permeability, and loss of villus tip surface area, correlates with microbial translocation and immune activation in HIV (71.5)

Abstract As early diagnosis and viremic control of HIV becomes more prevalent, the clinical focus has turned to preventing co-morbidities that include cardiovascular, hepatic, neurological, and metabolic abnormalities and immune exhaustion. Immune activation, as measured by leukocyte activation and soluble inflammatory mediators in circulation, is increased in HIV patients, even those on effective HAART therapy, and is a better predictor of disease progression and of all-cause mortality than viral load. Intestinal permeability, which often leads to microbial products in the bloodstream, may provide a cause for chronic inflammation in HIV patients. Here, we provide corroborating evidence of small intestinal and colonic permeability in a cohort of HIV patients with increased LPS, determined by measuring the excretion of various saccharides. Levels of lactulose and mannitol (small intestinal permeability) and sucralose (colonic permeability) were elevated (p=0.0014 and p&amp;lt;0.001, respectively) in the urine of HIV patients, independent of HAART status. Further analysis of the saccharide excretion profile revealed that HIV patients have a loss of villus tip surface area in the small intestine as compared to controls (p&amp;lt;0.001). These results were correlated to markers of bowel damage and microbial translocation (LPS Binding Protein, EndoCAb, sCD14, I-FABP) and immune activation (CRP, IL-6, IFN-α) and to clinical parameters in hopes of identifying key risk factors for disease progression.