Steroid use in measles: A retrospective cohort study during the 2017 outbreak in tertiary referral center, Rome and Latina, Italy.

INTRODUCTION: Since early January 2017, a new measles outbreak in Italy has been observed. The aim of the study was to compare features between adults and children measles cases and evaluate the effect of steroid treatment on the above parameters. METHODS: A retrospective multicenter, descriptive study was performed. We analyzed all patients admitted to the Department of Public Health and Infectious Diseases, Sapienza University, Rome and Latina, from January 2017 to December 2017 and discharged with diagnosis of measles. RESULTS: We identified 113 patients discharged with the diagnosis of measles infection cases of which 59 adults and 54 children (≤16 years). In adult population 32 patients (54 %) were males, with a median age of 30.5 years old and all unvaccinated (100 %). Keratoconjunctivitis 30 (50 %) was the most frequent complication. In pediatric population 27 (50 %) patients were males, with a median age of 3 years old. Information on measles vaccination status was available for only 21 (38.8 %) of cases. Keratoconjunctivitis 40 (74 %) was the most frequent complication. Analyzing the differences between adult and pediatric patients we found that children were significantly more likely to have keratoconjunctivitis and diarrhea as complications than adults in which the rate of thrombocytopenia and hepatitis was highest. Thirty-nine adult subjects (66 %) have been treated with systemic corticosteroids. CONCLUSIONS: Pediatric patients differ from adults in complications and liver involvement. Regarding steroids use, although there is no clear indication of steroid use during measles, there is no evidence of a worse outcome in our cases series.

Impact of vaccination and variants of concern on long COVID clinical phenotypes.

BACKGROUND: Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. METHODS: In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. RESULTS: A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p = 0.008) and an increase in cough (63% vs 17% p < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p = 0.004) and palpitations (12% vs 32% p < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms. CONCLUSION: This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination.

Long COVID: Clinical characteristics, proposed pathogenesis and potential therapeutic targets.

The emergence of persistent ill-health in the aftermath of SARS-CoV-2 infection has presented significant challenges to patients, healthcare workers and researchers. Termed long COVID, or post-acute sequelae of COVID-19 (PASC), the symptoms of this condition are highly variable and span multiple body systems. The underlying pathophysiology remains poorly understood, with no therapeutic agents proven to be effective. This narrative review describes predominant clinical features and phenotypes of long COVID alongside the data supporting potential pathogenesis of these phenotypes including ongoing immune dysregulation, viral persistence, endotheliopathy, gastrointestinal microbiome disturbance, autoimmunity, and dysautonomia. Finally, we describe current potential therapies under investigation, as well as future potential therapeutic options based on the proposed pathogenesis research.

TB specific intracellular cytokines production in Synovial liquid for diagnosis of tuberculous arthritis.

INTRODUCTION: Skeletal tuberculosis (TB) accounts for about 10 to 35% of extrapulmonary cases and the knee is the most frequent site after the spine and hip. The diagnosis is difficult and largely clinical. CASE PRESENTATION: This is a case of a young Pakistani man with a history of joint pain for about 4 years, who was diagnosed with chronic arthritis of the right knee. Microscopy of synovial fluid and conventional diagnostic tests to identify Mycobacterium tuberculosis were negative, while a non-classical method based on intracellular cytokine flow cytometry response of CD4 T-cells in synovial fluid helped us to address the diagnosis, which was subsequently confirmed by Polymerase Chain Reaction (PCR). CONCLUSIONS: Thanks to an innovative immunological approach, supported by PCR for detection of M. tuberculosis DNA, we were able to diagnose tuberculous arthritis of the knee, which allowed prompt initiation of treatment to reduce morbidity and mortality.

Longitudinal Assessment of Multiple Immunological and Inflammatory Parameters during Successful DAA Therapy in HCV Monoinfected and HIV/HCV Coinfected Subjects.

In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group. Activated CD4+ and CD8+ T-lymphocytes, mDCs, pDCs, MDC8 and classical, non-classical and intermediate monocytes were detected using flow cytometry. IP-10, sCD163 and sCD14 were assessed by ELISA while matrix metalloproteinase-2 (MMP-2) was measured by zymography. At baseline, increased levels of IP-10, sCD163 and MMP-2 were found in both HIV/HCV and mHCV patients compared to HD, whereas sCD14 increased only in HIV/HCV patients. After therapy, IP-10, sCD163 and sCD14 decreased, whereas MMP-2 persistently elevated. At baseline, activated CD8+ T-cells were high in HIV/HCV and mHCV patients compared to HD, with a decrease at SVR12 only in HIV/HCV patients. Activated CD4+ T-cells were higher in HIV/HCV patients without modification after DAAs therapy. These results suggest complex interactions between both viruses and the immune system, which are only partially reversed by DAA treatment.

Obesity in HIV infection: host-pathogen interaction.

OBJECTIVE: Both obesity and HIV infection are characterized by a state of chronic inflammation associated with increased morbidity and mortality. This review aims to assess the available literature on immune dysregulation in obesity and people with HIV infection (PWH). DESIGN: A systematic review of peer-reviewed literature. METHODS: We conducted a systematic literature search of PubMed, Embase, Scopus, and international conference abstracts for articles on the epidemiology of obesity in the general population and in PWH and the pathogenesis of obesity with a focus on inflammation and immune activation. RESULTS: Of the 631 articles selected after title review, 490 met the inclusion criteria and 90 were included in the final selection. The selected studies highlight the increasing prevalence of obesity in PWH and a substantial role for antiretroviral treatment (ART) in its development. Pathogenesis of obesity and its associated inflammation derives from disturbances in adipose tissue (AT) immune function, focused on T-cell and macrophage function, with a switch to pro-inflammatory immune phenotype and resulting increases in pro-inflammatory chemokines, which contribute to the development of metabolic syndrome. Although dysregulation of these pathways is seen in both obesity and HIV, there remains a lack of human studies on AT inflammation in HIV. CONCLUSION: Obesity is an emerging comorbidity in PWH, with a substantial overlap in immune dysregulation patterns seen in both conditions. How this immune dysfunction impacts on development of metabolic complications for both obesity and HIV infection, and whether targeting of AT-derived inflammation will improve outcomes in PWH requires further study.

Identification of Distinct Long COVID Clinical Phenotypes Through Cluster Analysis of Self-Reported Symptoms.

Background: We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID. Methods: This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters. Results: Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36-54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2-3] symptoms per individual in cluster 3 vs 6 [IQR, 5-7] and 4 [IQR, 3-5] in clusters 1 and 2, respectively; P < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning. Conclusions: Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.

An enhanced participant information leaflet and multimedia intervention to improve the quality of informed consent to a randomised clinical trial enrolling people living with HIV and obesity: a protocol for a Study Within A Trial (SWAT).

BACKGROUND: It is the investigator's responsibility to communicate the relevant information about a clinical trial to participants before they provide informed consent to take part. Systematic reviews indicate that participants often have a poor understanding of the concepts which are key to ensuring valid informed consent, such as randomisation and risks/discomforts. Paper-based participant information leaflets and informed consent forms (PIL/ICFs) are becoming longer and are often too complex for many participants. Multimedia interventions and enhanced PIL/ICFs have been trialled in an attempt to improve participants' understanding of various aspects of research studies. However, there is insufficient empirical evidence to determine how effective such interventions are. This protocol describes a study to evaluate whether an enhanced PIL/ICF and website help research participants to understand important information about a human immunodeficiency virus (HIV) randomised clinical trial. METHODS: This Study Within A Trial (SWAT) is a prospective, multi-centre, randomised, controlled, parallel-group study embedded in a host clinical trial. The host trial (the SWIFT trial; EudraCT: 2019-002314-39) is a prospective, multi-centre, randomised, open-label, controlled trial investigating if semaglutide along with dietary advice assists individuals with HIV and obesity to lose weight, compared to dietary advice alone. For the SWAT, participants will be randomised in a 1:1 ratio to either the control (standard PIL/ICF) or the intervention (an enhanced PIL/ICF and a website which includes animations). The enhanced PIL/ICF and website were developed in line with the guidance from organisations which promote plain English and accessible public-facing materials in conjunction with HIV Ireland, a HIV advocacy organisation, and our previous work on consent documents. The primary outcome of the SWAT is the quality of informed consent, assessed by a validated comprehension test-the modified Deaconess Informed Consent Comprehension Test (DICCT). The DICCT will be administered within 48 h of consent to the host trial. The secondary is recall, measured by the modified DICCT questionnaire scores 2 weeks post-consent to the host trial. DISCUSSION: The results of this SWAT will add to the methodological evidence base on the use of multimedia to improve the quality of informed consent to randomised clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04174755 . EudraCT 2019-002314-39. SWAT 160, Northern Ireland Hub for Trials Methodology Research SWAT repository (Clarke M, et al., Trials. 16:P209, 2015).

Dynamic Change and Clinical Relevance of Postinfectious SARS-CoV-2 Antibody Responses.

BACKGROUND: Although reports suggest that most individuals with coronavirus disease 2019 (COVID-19) develop detectable antibodies postinfection, the kinetics, durability, and relative differences between immunoglobulin M (IgM) and immunoglobulin G (IgG) responses beyond the first few weeks after symptom onset remain poorly understood. METHODS: Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity, specificity, and relationship with disease severity and mapped the kinetics of antibody responses over time using generalized additive models. RESULTS: We analyzed 1001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1%-47.1%) early (<10 days) after symptom onset but increased to >80% after 10 days. IgM positivity increased earlier than IgG-targeted assays, but positivity peaked between days 32 and 38 post-onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analyzed, with a more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal/cutoff 4.20 [0.75-17.93] vs 1.07 [0.21-5.46]; P = .048). CONCLUSIONS: This study suggests that postinfectious antibody responses in those with confirmed COVID-19 begin to decline relatively early postinfection and suggests a potential role for higher IgM levels early in infection in the prediction of subsequent disease severity.

Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV.

BACKGROUND: Whilst reporting improved renal and bone safety profiles, studies have noted changes in lipid profiles among people living with HIV (PLWH) receiving antiretroviral therapy (ART) switching away from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We aimed to characterize changes in lipids observed after switching to TAF-containing ART in a real-world setting. METHODS: A prospective study on PLWH enrolled in the UCD-ID Cohort study who switched to TAF-containing ART. Routine laboratory data [including lipids (total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides], ART history and use of lipid-lowering therapy (LLT) were analysed preswitch and postswitch to TAF. Dyslipidaemia was classified according to the National Cholesterol Education Program-Adult Panel III (NCEP-ATP III). Change in lipid parameters and change in the proportion of individuals with dyslipidaemia postswitch was assessed using the paired t-test and the Stuart--Maxwell test, respectively. RESULTS: Of 775 PLWH enrolled in the cohort, 238 switched to TAF containing ART, of whom 194 had both preswitch and postswitch lipids measured a median (IQR) 24 (14-41) weeks postswitch to TAF. TC, LDL, HDL, triglycerides and TC : HDL ratio significantly increased postswitch [mean change (SE) mmol/l; +0.37 (0.06), P < 0.001; +0.25 (0.06), P < 0.001; +0.05 (0.02), P = 0.003, +0.13 (0.07), P = 0.02, and +0.16 (0.08), P = 0.013) respectively]. There were significant increases in the proportions of PLWH with more severe dyslipidaemia postswitch across TC and LDL (both P < 0.001). CONCLUSION: These data suggest clinically relevant, worsening lipid profiles postswitch to TAF, with a larger proportion of PLWH exceeding recommended lipid thresholds postswitch. How these changes will impact on cardiovascular risk or need for LLT remains to be determined.

Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection.

Chronic hepatitis C virus infection leads to the activation of innate immunity, a key component in HCV fibrosis. In the past, the use of IFN-based treatment regimens did not permit an adequate evaluation of the impact of HCV clearance on immune cells, because of their antiviral and immunomodulatory properties. The recent development of direct-acting antiviral (DAA) therapy, which is associated with high rates of sustained virological response, enables a more accurate analysis of the immunological modifications following HCV eradication. We studied the dynamics of blood myeloid dendritic cells, monocytes, slan-DCs, and T lymphocytes during IFN-free and IFN-based regimens in hepatitis C virus infection.

Effectiveness of Switching to Darunavir/Cobicistat in Virologically Suppressed HIV-Positive Patients Receiving Ritonavir-Boosted Protease Inhibitor-Based Regimen: The "STORE" Study.

OBJECTIVE: This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated. SETTING: Prospective, multicenter, single-country, noninterventional cohort study. METHODS: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA <50 copies/mL since at least 6 months. The primary endpoint, defined as HIV-1 RNA <50 copies/mL, was measured at 48 ± 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response algorithm. Biochemical parameters, including DRV trough samples, were collected as per clinical practice and measured using high-performance liquid chromatography. RESULTS: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA <50 copies/mL at 48 weeks; using the time to loss of virological response algorithm, 82.7% maintained virological suppression. Virological failure was observed in 6 patients (1.8%). Adverse event-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130 to 113.5 mg/dL, P = 0.0254) and high-density lipoprotein cholesterol (48 to 49 mg/dL, P < 0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439) ng/mL, higher in women than in men (4221 vs. 2634 ng/mL, P = 0.046). CONCLUSIONS: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of virological failure and adverse events due to its high tolerability and improvement in triglycerides.

Myeloid and lymphoid activation markers in AIDS and non-AIDS presenters.

HIV infection is characterized by a state of chronic activation of the immune system, which is not completely reversed by antiretroviral treatment (ART). The aim of this study was to assess myeloid and lymphoid activation markers during HIV infection, before and one year after ART initiation, in AIDS and non-AIDS presenters. Treatment naïve HIV positive patients were enrolled in this study. Myeloid dendritic cell (mDC), plasmacytoid dendritic cell (pDC), slanDC, monocyte and T-lymphocyte cell counts and activation status, were assessed by flow cytometry in peripheral blood samples. Soluble (s)CD14 and sCD163 were assessed in plasma samples using ELISA assays. Statistical analyses were performed using GraphPad Prism and Minitab Express. Thirty-four ART naïve HIV-1 infected subjects were enrolled in this study (22 non-AIDS and 12 AIDS presenters). Seventeen healthy donors (HD) were included as control group. Although circulating mDC levels resulted unchanged, HLA-DR expression was decreased on mDCs of HIV positive subjects compared to HD (p < 0,0001). AIDS presenters showed the lowest level of expression of HLA-DR on mDCs. Circulating levels of pDCs were decreased in HIV patients compared to HD (p < 0,001), without any changes in HLA-DR expression. SlanDC cell counts were extremely reduced in AIDS presenters, compared to non-AIDS presenters and HD (p < 0,01 and p < 0,0001, respectively) and showed higher HLA-DR expression in HIV patients compared to HD (p < 0,01). Intermediate monocyte (IM) cell counts were increased in AIDS and non-AIDS presenters compared to HD (p < 0,001 and p < 0,001 respectively). Furthermore, IM expansion was directly correlated to HIV viral load (p = 0,036) and independent from CD4 cell counts and activation levels. Plasma concentrations of sCD14 and sCD163 resulted increased in HIV infected subjects compared to HD (p < 0,0001 and p < 0,001), with the highest levels observed in AIDS presenters. After 1 year, ART was able to increase pDC and decrease IM absolute cell counts and modify HLA-DR expression on mDCs and slanDCs, approaching the levels observed in HD. ART reduced also CD4 and CD8 activation levels. In conclusion, in untreated HIV infected subjects circulating dendritic cells resulted altered either in numbers or in HLA-DR expression, especially in AIDS presenters. IM absolute counts were equally increased in AIDS and non-AIDS presenters. ART was able to reduce myeloid and lymphoid inflammation in both advanced and non-advanced HIV patients, confirming the role of ART in hampering disease progression and immune activation associated non-AIDS events.

Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection.

BACKGROUND AND AIMS: Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. METHODS: sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. RESULTS: At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. CONCLUSIONS: These results indicate that, despite the resolution of symptoms, an important macrophage/monocyte activation persists in measles patients, even after two months from infection.

Clearance of human papillomavirus related anal condylomas after oral and endorectal multistrain probiotic supplementation in an HIV positive male: A case report.

INTRODUCTION: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity. CONCLUSION: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route.

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon.

BACKGROUND AND AIMS: Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). METHODS: sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. RESULTS: At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with high sCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. CONCLUSIONS: These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection.

Active HCV infection is associated with increased circulating levels of interferon-gamma (IFN-γ)-inducible protein-10 (IP-10), soluble CD163 and inflammatory monocytes regardless of liver fibrosis and HIV coinfection.

BACKGROUND AND OBJECTIVE: Interferon-gamma (IFN-γ)-inducible protein-10 (IP-10), soluble (s) CD163 and sCD14 play an important role in the pathogenesis of HCV and HIV infection and are involved in inflammation and liver fibrosis. The aim of the present study was to evaluate at a single time point, plasma soluble biomarkers and inflammatory monocytes subsets in different groups of subjects: (i) HIV monoinfected patients on suppressive ART; (ii) HIV/HCV coinfected patients on ART, with undetectable HIV viremia (including either subjects who had active HCV replication or those who cleared HCV); (iii) HCV monoinfected individual with active viral replication. METHODS: Hundred and twenty-nine plasma samples were analyzed including HCV and HIV monoinfected patients, HIV/HCV coinfected patients, with active HCV infection (AHI) or with HCV viral clearance (VHC) and healthy donors (HD). Levels of IP-10, sCD163 and sCD14 were measured by ELISA. Absolute cell counts of monocyte subpopulations were enumerated in whole blood by using flow cytometric analyses. RESULTS: IP-10 and sCD163 plasma levels were higher in HCV monoinfected and in AHI coinfected pts compared to HIV monoinfected and HD, whereas sCD14 levels were higher only in HIV monoinfected patients. Considering the degree of fibrosis, sCD163 and sCD14 levels positively correlated with kPa values (as assessed by fibroscan) and FIB-4 in HCV monoinfected group. On the other hand, IP-10 did not correlate with the fibrosis stage and it was found increased also in patients with low fibrosis. Moreover, we found an increase of the inflammatory NCM subset, in non-cirrhotic HCV subjects, while no alterations were observed in HIV, AHI and VHC. CONCLUSIONS: Our study suggests a scenario in which active HCV infection is associated with a strong pro-inflammatory state, even in the initial stage of liver fibrosis, regardless the presence of HIV coinfection, thus underlying the need of an early anti-HCV treatment.

Blood Myeloid Dendritic Cells and slanDC in Antiretroviral Therapy- Suppressed HIV-Infected Patients.

Myeloid dendritic cells (mDCs) play a complex role in HIV infection regardless of viral replication. The aim of our study was to analyse mDCs in long term antiretroviral therapy (ART)- suppressed HIV-infected patients. We evaluated the numbers of mDCs and slanDC in the context of different degree of CD4+ T cell recovery, persistent T cell activation (as HLA-DR+/CD3+ expression) and monocyte-macrophage activation assessed in terms of circulating levels of both sCD14 and sCD163. We enrolled 72 aviremic patients under effective ART and 34 healthy donors (HD). Patients were divided into two groups on the bases of ΔCD4, indicating the difference between the value of CD4 at the time of sampling and CD4 nadir. Higher levels of mDCs and slanDC were found in patients with ΔCD4>200/mmc in comparison to HD. In those patients also an increased level of sCD14 was found, whereas sCD163 seemed to be at normal levels. An augmentation of activated CD4 T lymphocytes was found, although less pronounced in patients with ΔCD4<200/mmc. In conclusion, our findings showed an expansion of mDCs with a shift to inflammatory slanDC that could sustain both microbial translocation and HIV latency in CD4 T cells.