Τρίτη 27 Δεκεμβρίου 2022

Transmitted drug resistance to integrase based first-line HIV antiretroviral regimens in the Mediterranean Europe

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Abstract
Objective
To study the prevalence of transmitted drug resistance (TDR) to INSTIs and NRTIs, and of clinically relevant resistance (CRR), in newly-diagnosed people with HIV (PWH) naïve to antiretroviral therapy (ART) in Europe.
Methods
MeditRes HIV is a consortium that includes ART naïve PWH newly diagnosed in France, Greece, Italy, Portugal, and Spain during the years 2018-2021. Reverse transcriptase (RT) and Integrase (INSTI) sequences were provided by participating centers. To evaluate the prevalence of surveillance drug resistance mutations (SDRM) we used the CPR tools from Stanford HIV-website. To evaluate clinically relevant resistance (CRR), defined as any resistance level >= 3, we used the Stanford v.9.1HIVDB Algorithm.
Results
We included 2705 PWH, 72% men, median age of 37 (IQR, 30-48); 43.7% infected by non-B subtypes. The prevalence of INSTI-SDRMs was 0.30% (T66I, T66A, E92Q, E138T, E138K, Y143R, S147G and R263K, all n = 1), and of NRTI-SDRMs was 5.77% (M184V n = 23, 0.85%; M184I n = 5, 0.18%; K65R/N n = 3, 0.11%; K70E n = 2, 0.07%; L74V/I n = 5, 0.18%; any TAMs n = 118, 4.36%). INSTI-CRR was 2.33% (0.15% dolutegravir/bictegravir; 2.29% raltegravir/elvitegravir), and 1.74% to first-line NRTIs (0.89% tenofovir/tenofovir alafenamide fumarate; 1.74% abacavir; 1.07% lamivudine/emtricitabine).
Conclusions
We present the most recent data on TDR to integrase based first-line regimens in Europe. Given the low prevalence of CRR to second generation integrase inhibitors and to first-line NRTIs, in the years 2018-2021 it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second generation integrase inhibitors.
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Risk of waning humoral responses after inactivated or subunit recombinant SARS‐CoV‐2 vaccination in patients with chronic diseases: Findings from a prospective observational study in China

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Abstract

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [C I]: 0.46–0.93), cancer (OR: 0.65; 95% CI: 0.42–0.99), and diabetes (OR: 0.50; 95% CI: 0.28–0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11–0.76), cancer (OR: 0.38; 95% CI: 0.23–0.62), and diabetes (OR: 0.37; 95% CI: 0.20–0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.

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Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment

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Abstract

Nirmatrelvir/ritonavir (NMV-r) is an effective anti-SARS-CoV-2 agent and has been recommended in the treatment of non-hospitalized patients with COVID-19. In rare occasions, some patients experience virologic and symptomatic rebound after initial resolution, which we call COVID-19 rebound after NMV-r. Although COVID rebound can also occur after molnupiravir treatment or even no antiviral treatment, we have more serious concern about the rebound after NMV-r, which remains the most effective antiviral. Due to a lack of information about its frequency, mechanism, outcomes, and management, we conducted this review to provide comprehensive and updated information to address these questions. Based on the limited evidence, the incidence of COVID-19 rebound after NMV-r was less than 2%, and most cases developed 5–15 days after initiating NMV-r treatment. Almost all reported cases had mild symptoms, and the clinical condition gradually subsided without additional treatment. Overall, the clinical outcome was favourable, and only a small number of patients required emergency department visits or hospitalization. Regarding virologic rebound, culturable SARS-CoV-2 with possible transmission was observed, so re-isolation may be needed.

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CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID‐19 therapy

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Abstract

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. SARS-CoV-2 is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little information is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A ge ne expression during 3-15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

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Multisystem inflammatory syndrome in adults: Characteristics, treatment, and outcomes

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ABSTRACT

Following the rapidly increasing number of multisystem inflammatory syndromes in children (MIS-C), a similar clinical scenario has been observed in adult patients. Although its prevalence is low and probably related to underdiagnosis, its development can be associated with high mortality. Multisystem inflammatory syndrome in adults (MIS-A) can develop following both asymptomatic and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and in previously healthy people. Like MIS-C, MIS-A is a multisystem disease that can involve the cardiovascular, respiratory, gastrointestinal, dermatologic, hematologic, and neurologic systems. In addition to the clinical manifestations, the diagnosis of MIS-A requires laboratory evidence of inflammation and SARS-CoV-2 infection. The appropriate treatment for MIS-A remains unclear; anti-inflammatory agents, including intravenous immunoglobulin and corticosteroids, are commonly used. However, there are still many unknow ns regarding MIS-A. Further studies are needed to determine the true prevalence, pathogenesis, and effective treatment for MIS-A.

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Recall of Daptomycin for Injection 500 mg/vial and Daptomycin for Injection 350 mg/vial Lot # R2200232 Due to Product Mix-Up

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Accord Healthcare, Inc. is voluntarily recalling a single lot of Daptomycin for Injection 500 mg/vial, and Daptomycin for Injection 350 mg/vial product contained in cartons imprinted with lot # R2200232 Exp: 01/2025 to the consumer/user level.
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Viruses Responsible for Acute Respiratory Infections Before (2016‐2019) and During (2021) Circulation of the SARS‐CoV‐2 virus in Pediatric Patients in a Reference Center at Barranquilla Colombia: A Pattern Analysis

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Summary

Objective

To evaluate the behavior of the viruses responsible for acute respiratory infections before (2016-2019) and after (2020-2021) the start of the circulation of the SARS-CoV-2 virus in pediatric patients treated at a reference center from Barranquilla, Colombia.

Materials and methods

A descriptive observational study was carried out, and data were obtained by reviewing the influenza-like illness and severe acute respiratory infection database in the pediatric population of the sentinel surveillance reference center in the district of Barranquilla during the years 2016 - 2021, applying inclusion and exclusion criteria.

Results

During 2016-2019, the average age of individuals was 1.3 (±1.7) years, during 2021, it was 2.3 (±3.5) years. The distribution by sex was similar, predominantly male. August and February were the months with the highest record of symptoms for 2016-2019 and 2021, respectively, the most frequent being cough, fever, shortness of breath, and diarrhea. By 2021 there was a higher use of antibiotics and antivirals reported than in 2016-2019. Most patients tested negative for viral detection. When comparing the percentage of viruses detected by age group and years of detection, positivity was lower in 2021 by every age group, and respiratory Syncytial Virus (RSV) was the most frequently detected.

Conclusions

There was less virus positivity in viral detection tests in the pediatric population in 2021. RSV persists as the main etiology affecting this population, especially infants. The use of antibiotic therapy in viral infections continues to be a problematic practice in their management. Sentinel surveillance can be strengthened throughout the country.

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The HBV web: An insight into molecular interactomes between the Hepatitis B virus and its host en route to hepatocellular carcinoma.

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ABSTRACT

Hepatitis B virus (HBV) is a major aetiology associated with the development and progression of hepatocellular carcinoma (HCC), the most common primary liver malignancy. Over the past few decades, direct and indirect mechanisms have been identified in the pathogenesis of HBV-associated HCC which include altered signaling pathways, genome integration, mutation-induced genomic instability, chromosomal deletions and rearrangements. Intertwining of the HBV counterparts with the host cellular factors, though well established, needs to be systemized to understand the dynamics of host-HBV crosstalk and its consequences on HCC progression. Existence of a vast array of protein-protein and protein-nucleic acid interaction databases has led to the uncoiling of the compendia of genes/gene products associated with these interactions. This review covers the existing knowledge about the HBV-host interplay and brings it down under one canopy emphasizing on the HBV-host interactomics; and thereby highlights new strategies for therapeutic advancements against HBV-induced HCC.

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Infectivity of pseudotyped SARS‐CoV‐2 variants of concern in different human cell types and inhibitory effects of recombinant spike protein and entry‐related cellular factors

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Abstract

Since the report of the first COVID-19 case in 2019, SARS-CoV-2 variants of concern (VOCs) have continued to emerge, manifesting diverse infectivity, evasion of host immunity and pathology. While ACE2 is the predominant receptor of SARS-CoV-2, TMPRSS2, Kim-1, NRP-1, CD147, furin, CD209L and CD26 have also been implicated as viral entry-related cofactors. To understand the variations in infectivity and pathogenesis of VOCs, we conducted infection analysis in human cells from different organ systems using pseudoviruses of VOCs including Alpha, Beta, Gamma and Delta. Recombinant spike S1, RBD, ACE2, Kim-1 and NRP-1 proteins were tested for their ability to block infection to dissect their roles in SARS-CoV-2 entry into cells. Compared with wild type SARS-CoV-2 (WT), numerous VOCs had significant increases of infectivity across a wide spectrum of cell types. Recombinant ACE2 protein more effectively inhibited the infection of VOCs including Delta and Omicron (BA .1 and BA.2) than that of WT. Interestingly, recombinant S1, RBD, Kim-1 and NRP-1 proteins inhibited the infection of all pseudoviruses in a manner dependent on the levels of ACE2 expression in different cell types. These results provide insights into the diverse infectivity of SARS-CoV-2 VOCs, which might be helpful for managing the emergence of new VOCs.

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No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection

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Abstract
Background
IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.
Methods
We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984–1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies.
Results
We found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76–1.11]), cytomegalovirus infection (0.94 [.71� �1.24]), herpes simplex virus infection (1.37 [.68–2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count.
Conclusions
The absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.
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