A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy.

Cardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) >5%), revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by Computed tomography angiography scan (CTAScan) as total (TPV) and low attenuated plaque volume (LAPV) in ART-treated PLWH (HIV+) versus uninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4 + T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells, were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1 and triglyceride levels, lower Th17/Treg ratios, and classical monocyte expansion. Among HIV + , TPV + versus TPV - exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9 low HLADR high monocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9 low HLADR high monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C.

This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1ß, IL-15, IFN-γ, IL-4, IL-10, TGF-ß, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-ß and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

Adverse effects of direct acting antiviral-based regimens in chronic hepatitis C patients: a Brazilian experience.

Background Direct-acting antivirals (DAA) are currently used for the treatment of chronic hepatitis C (HCV). However, few studies describe the adverse effects (AE) associated with DAA therapy in "real-word" cohorts. Aim To evaluate AE in Brazilian chronic HCV patients after DAA-therapy. Setting A reference center for hepatitis treatment in Rio de Janeiro, Brazil. Methods An observational "real-world" study was conducted with 102 chronic HCV patients undergoing DAA therapy for 12 or 24 weeks. The self-reported AE were correlated with cirrhosis status, genotype, age, current therapeutic schemes and comorbidities. Serious AE were also investigated. Main outcome measure Frequency of AE during DAA therapy. Results Overall, mean ± SD age was 60.9 ± 9.4 years, 67% were females, HCV-genotype 1 was the most prevalent (81%) and 74% were cirrhotic. Moreover, all patients reached sustained virological response. About 90% of patients reported at least one AE associated with current treatment, with a mean of 2.7 symptoms per patient. The most frequently reported AE were fatigue (43%), headache (42%), neuropsychiatric symptoms (30%) and nausea (26%). Furthermore, hemoglobin < 12 mg/dL was the most frequent (38%) laboratory abnormality observed. Neuropsychiatric symptoms were the only AE significantly different in treatment-experienced group when compared to naïve patients (41.7 vs. 12.5, P = 0.002). The higher frequency of AE did not correlate with the presence of previous treatment, cirrhosis, genotype, age, current therapeutic schemes with DAA or comorbidities. Conclusion DAA-based therapeutic regimens demonstrated safety in a Brazilian "real-world" cohort of chronic hepatitis C patients.

Metabolic syndrome components and estimated glomerular filtration rate based on creatinine and/or cystatin C in young adults: A gender issue?

AIMS: This work aims to identify correlations between estimated glomerular filtration rate (eGFR) based on creatinine and/or cystatin C (Cr, CysC) with metabolic syndrome (MS) components in young adults, according to gender. MATERIAL AND METHODS: This is a cross sectional study, where young adults aged between 18 and 30 were matched by gender, age and body mass index. All subjects underwent clinical evaluation and blood sampling for laboratory measurements. MS was determined according to the JIS criteria. The eGFR was estimated using CKD-EPI equations (eGFRCr; eGFRCysC; eGFRCr-CysC). RESULTS: We evaluated 78 subjects with a mean age of 24.5 years. 10.2% had MS, with higher incidence among males (15.4% ♂ vs. 5.1% ♀). Elevated waist circumference was the MS component most observed. Significant correlations (Pearson; p<0.05) between eGFR and metabolic markers were observed only in males. In addition, we observed a significant association between the increase of MS components and the decay of eGFRCr and eGFRCr-CysC (zero vs. two or more components, ANOVA, p<0.05) only among males. CONCLUSION: eGFR decay associated with components of MS and insulin resistance in young male adults could represent a worrying specific risk and indicate that further studies are needed to better understand these findings.