Improvement of neuropsychological performances and reduction of immune-activation markers after probiotic supplementation and change of life-style in an HIV positive male: targeting the microbiota to act on gut-brain axis

The gut-brain axis is widely in uenced by the intestinal microbiota and dysbiosis is consequently associated with a large dysregulation of its functions. Probiotic supplementation, reducing the harmful effects of dysbiosis, has shown positive effects not only on gut and brain functions, but also on the control of the dangerous effects of immune activation. Mounting evidence has shown that neurocognitive impairment can be a secondary to the impairment of the microbiota-gut-brain axis in HIV positive patients. In this case report we analyzed the im- provement of neurocognitive performances associated with a reduction of levels of peripheral immune-activa- tion, after 6 months of probiotic supplementation. In this case, the achieved result may have been in uenced by a more comprehensive modi cation of the patient’s lifestyle with the introduction of a controlled diet and regular physical activity. Our observations suggest that integrate antiretroviral therapy and non-pharmacological tools into an overall approach, can be a useful strategy to control some non-AIDS related diseases

Assessment of biventricular function by three-dimensional speckle tracking echocardiography in adolescents and young adults with human immunodeficiency virus infection. a pilot study.

Background. The purpose of the study was to assess biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in adolescents and young adults with human immunodeficiency virus infection (HIV) on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction. Methods. Twenty-one patients aged 12 to 39years with HIV, 21 normal controls of the same age and sex, and 21 patients with idiopathic non-ischemic dilated cardiomyopathy (DCM) were studied with 3DSTE. All HIV patients were stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection, and were on highly active antiretroviral therapy (HAART) with good immunological control. Standard echocardiographic measures of LV-RV function were assessed. 3D LV global longitudinal strain (GLS), circumferential strain, radial strain and LV twist (TW) were calculated. Global area strain (GAS) was calculated by 3DSTE as percentage variation in surface area defined by the longitudinal and circumferential strain vectors. 3D right ventricular (RV) global and free-wall longitudinal strain were obtained. Results. LV GLS and GAS were lower in HIV patients compared to normal controls (p=0.002, and p=0.01, respectively). There were no significant differences in LV ejection fractions between the groups. There was a weak positive correlation between LV GLS and age (r=0.215, p=0.034) and a weak negative correlation between LV GLS and nadir-CD4 T-cells count (r=0.198, p=0.043). DCM patients had more marked and widespread reduction in LV GLS and GAS compared to controls (p<0.001), whereas in HIV patients LV strain impairment (p<0.05) was more localized in basal and apical regions. RV free-wall longitudinal strain was significantly reduced in HIV patients when compared with the control group (p=0.03). No patient had pulmonary systolic pressure higher than 35mmHg. Conclusions. Three-dimensional speckle tracking echocardiography may help to identify HIV patients at high cardiovascular risk allowing early detection of biventricular dysfunction in the presence of normal LV ejection fraction and in the absence of pulmonary hypertension. LV strain impairment in HIV patients is less prominent and widespread compared to DCM patients

Modulation of tryptophan/serotonin pathway by probiotic supplementation in human immunodeficiency virus-positive patients: preliminary results of a new study approach

Background: To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1–infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy–treated patients and the subsistence of an interplay with inflammation. Methods: We conducted a pilot study that included 8 HIV-positive subjects. We collected blood and fecal samples before and after 6 months of probiotic supplementation, to measure the level of serotonin in serum and tryptophan in stool, the expression of CD38 and HLADR on peripheral CD4+ T lymphocytes (as immune activation markers), the expression of indoleamine 2,3-dioxygenase 1 messenger RNA (mRNA) and IFN-γ mRNA (as markers of tryptophan metabolism and systemic inflammation). Results: After probiotic supplementation, we observed a significant increase in concentration of serum serotonin (P=.008) and a decreased level of tryptophan in plasma. Moreover, a significant reduction in CD38 and HLA-DR expression on the surface of peripheral CD4+ T cells (P=.008) and a reduced expression of indoleamine 2,3-dioxygenase 1 mRNA on peripheral blood mononuclear cells (P=.04) were observed. Conclusions: Considering that this probiotic (Vivomixx® in EU; Visbiome® in USA) has an influence on tryptophan metabolism, larger studies on this topic are needed

Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic hepatitis C virus infection

CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper-1-like signature program in chronic (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV infection

Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients

Background People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach. Materials and methods In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV + individuals (45 males, age 48 (42.5–48) years) on effective cART (CD4 + cell count: 450 cells/µL (IQR: 328–750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5–56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly. Results The ECV was significantly higher in HIV + patients than in the control group (ECV: 31% (IQR: 28%-31%) vs. 27.4% (IQR: 25%-28%), p < 0.001). The duration of cART (standardized β = 0.56 (0.33–0.95), p = 0.014) and the years of exposure to HIV infection (standardized β = 0.53 (0.4–0.92), p < 0.001), were positively and strongly associated with ECV values. Differences in ECV (p < 0.001) were also observed regarding the duration of cART exposure (< 5 years, 5–10 years and > 10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33–0.89), p = 0.084). Conclusions HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH

Strumenti per la valutazione del rischio cardiovascolare in relazione allo stato di ateromasia coronarica in soggetti con infezione da HIV

Nonostante l'avvento dei farmaci antiretovirali, l'infezione da HIV rimane a tutt'oggi uno dei principali problemi di carattere sanitario a livello globale. La prognosi e lo spettro delle complicanze nei soggetti con infezione da HIV appaiono al giorno d'oggi profondamente differenti rispetto a quanto osservato nell'era pre HAART, ad ogni modo oggi i pazienti HIV positivi presentano un più elevato rischio di presentare comorbidità non correlate alla condizione di AIDS, rappresentate per lo più da patologie legate all'invecchiamento, e tra queste la malattia cardiovascolare risulta essere una delle più frequenti. L'incidenza di infarto acuto del miocardio in questa popolazione risulta essere raddoppiata rispetto a quanto si osserva nella popolazione generale, con un'età media di insorgenza precoce rispetto ai soggetti HIV negativi. La patogenesi di tale condizione risulta essere in parte conseguente allo stato di aumentata infiammazione e immunoattivazione sistemica che è propria dei soggetti con infezione da HIV, mentre almeno in parte è ascrivibile agli effetti metabolici di alcuni dei farmaci utilizzati nel trattamento dell'infezione. Ad ogni modo, il rischio cardiovascolare in questa popolazione risulta essere più elevato rispetto a quanto osservato nella popolazione generale, anche per quanto riguarda gli individui che non presentano i tradizionali fattori di rischio cardiovascolare. In questa prospettiva, il presente studio si propone di valutare lo stato di malattia coronarica subclinica in una popolazione di soggetti con infezione da HIV a basso rischio cardiovascolare e di investigare l'applicabilità di metodi per la valutazione di tale rischio

Assessment of biventricular function in human immunodeficiency virus infection in adolescents and young adults by three-dimensional speckle tracking echocardiography

Background. The pathogenesis of left ventricular (LV) dysfunction in HIV patients includes cardiac direct effects of HIV, the presence of autoantibodies, myocardial inflammatory response to viruses, other infections related to the immune status of patients and side effects associated with antiretroviral drugs or other drugs used for the management of HIV. The purpose of our study was to evaluate biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in HIV-infected patients on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction. Methods. Sixteen patients aged 12 to 31years with human immunodeficiency virus infection and 16 normal controls of the same age and sex were studied with 3DSTE. All patients were stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection. Patients were on HAART with good immunological control. Standard echocardiographic measures of LV-RV function were assessed. Tricuspid annular systolic plane excursion (TAPSE) was measured by M-mode of the lateral tricuspid valve annulus. LV global longitudinal, circumferential and radial strains were calculated. Global area strain (GAS) was calculated by 3DSTE as percentage variation in surface area defined by the longitudinal and circumferential strain vectors. Right ventricular (RV) 3D global and free-wall longitudinal strain were obtained. Data analysis was performed offline. Results. LV global longitudinal strain and GAS were lower in HIV patients compared to normal controls (-15.9% vs -19.1%, p=0.013, and -33.9% vs -38.7%, p=0.004, respectively). There were no significant differences in ejection fractions between the groups. There was a trend toward reduced TAPSE in HIV patients compared to controls (20.2±2.3mm vs 23.4±2.6mm, p=0.08). RV free-wall longitudinal strain was significantly reduced in HIV patients when compared with the control group (-19.8% vs -23.7%, p=0.025). No patient had pulmonary systolic pressure higher than 35mmHg. There was no correlation between echocardiographic parameters and selected biomarkers. Conclusions. Three-dimensional speckle tracking echocardiography may help to identify HIV patients at high cardiovascular risk allowing early detection of biventricular dysfunction in the absence of pulmonary hypertension