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

alexandrossfakianakis shared this article with you from Inoreader Transmitted drug resistance to integrase based first-line HIV antiretroviral regimens in the Mediterranean Europe via Clinical Infectious Diseases Advance Access 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. View on Web

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Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment

alexandrossfakianakis shared this article with you from Inoreader Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Multisystem inflammatory syndrome in adults: Characteristics, treatment, and outcomes via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader 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 via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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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.

alexandrossfakianakis shared this article with you from Inoreader The HBV web: An insight into molecular interactomes between the Hepatitis B virus and its host en route to hepatocellular carcinoma. via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader 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 via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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