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BackgroundMinority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR).MethodsAll the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load 20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count

Background: Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen.Methods: We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) algorithm.Results: Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine (n = 81) and abacavir/lamivudine or emtricitabine (n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm3. The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L (n = 1), I84V (n = 2) and N88S (n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L (n = 2), D67N (n = 3), K70R (n = 1), L74I/V (n = 3), M184V/I (n = 16), L210W (n = 1), T215Y/F (n = 3) and K219Q/E (n = 2).Conclusions: Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients. [ABSTRACT FROM AUTHOR]

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021-2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0-5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF., Methods: A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50 copies/mL or one VL of ≥200 copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms., Results: Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive., Conclusions: This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH., (© 2024 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

In 2022, the World Health Organization (WHO) estimated that hepatitis B virus (HBV) infections caused 1.5 million deaths, mostly attributable to complications from chronic infections, cirrhosis and hepatocellular carcinoma (HCC). Despite the availability of a vaccine, 296 million people were chronically infected in 2019. Asia and Africa are the continents most affected by this infection, with around 100 million people infected in Africa as a whole.Hepatitis Delta or D virus (HDV), which is a "satellite" virus of HBV, is often misunderstood and its diagnosis remains neglected. However, it is associated with acute fulminant forms and chronic forms of hepatitis leading to a more rapid evolution towards cirrhosis and HCC than during HBV mono-infection. Research on these two viruses HBV and HDV has progressed a lot in recent years, and new treatments are currently in development.In people living with the human immunodeficiency virus (PlHIV), liver disease is a major cause of morbidity and mortality. Due to common modes of transmission, dual or triple HIV/HBV or HIV/HBV/HDV infections are relatively common, particularly in HBV endemic regions such as Africa. However, while today most co-infected patients benefit from effective treatment against both HIV and HBV, the latter is not active against HDV. In Africa, hepatitis B and D have already been the subject of several studies. However, the frequency and clinical consequences of these co-infections have been little studied in the general population and in PlHIV.This review seeks to update the epidemiological and clinical data and the therapeutic perspectives of HDV co-infections or triple infections (HIV-HBV-HDV) in Africa., (Copyright © 2023 SFMTSI.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of rapid diagnostic testing to identify individuals with SARS-CoV-2 infections and to limit the spread of the virus. Many molecular assays have become commercially available to cope with this surging demand for timely diagnosis of COVID-19 cases, but identifying individuals requires accurate diagnostic tools. We compared the performance of three molecular SARS-CoV-2 assays: Aptima™ SARS-CoV-2 assay running on the Panther system (Hologic), an in-house assay (Laboratory Developed Test, LDT) running on the Fusion module of the Panther Fusion system (LDT-Fusion; Hologic), and the R-GENE® SARS-CoV-2 assay (bioMérieux). In addition, we also evaluated the turnaround time. This parameter is crucial to managing the SARS-CoV-2 diagnosis and represents a key point in the quality management at the laboratory. Aptima™ and LDT-Fusion assays exhibited an excellent positive percent agreement (PPA) (100.0%), while the R-GENE® assay showed a slightly decreased PPA (98.2%). The Hologic assays have a higher throughput with less hands-on time than the R-GENE® assays (24-25 vs. 71 min). Both Hologic assays are used on a fully automated random-access testing system with on-demand testing capabilities that avoid run series, unlike the R-GENE® assay. Automated random-access testing systems should be preferred during periods of high SARS-CoV-2 prevalence., (© 2022 Wiley Periodicals LLC.)

The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-β1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-β1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity., (© 2022. The Author(s).)

Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate promptly after diagnosis. The case raises questions about the use of antiviral treatment in AHB. This is generally not recommended in AHB, but it would be potentially useful in pregnant women to reduce the risk of chronic HB infection and could also prevent the transmission of the maternal precore mutation, thus reducing the significant risk of fulminant hepatitis in the infant. This case also highlights the impact of the hepatitis B virus (HBV) genotype and precore/core mutations on the clinical course of the disease., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To assist in the clinical management of patients and to support infection control, we tested the use of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care antigen test (AgPOC) for unplanned hospitalization, coupled with a nucleic acid amplification test (NAAT) using specimens collected at the same time upon arrival. The aim of this study was to assess the performance of the AgPOC in this specific use compared to NAAT for SARS-CoV-2 diagnosis, in the context of the low prevalence of infection. For 5 months (between two peaks in France of the SARS-CoV-2 pandemic), all patients admitted who undertook the AgPOC/NAAT paired tests were included in the study. AgPOC performances were determined considering the clinical status and the delay of symptoms onset. NAAT and AgPOC results were available for 4425 subjects. AgPOC results showed a homogeneous specificity (>97%) but a low sensitivity at 45.8%. Considering the national guidelines, sensitivity dropped to 32.5% in cases of symptomatic patients with symptoms older than 5 days or more. This study shows the poor performance of AgPOC for entry screening of patients in hospitals. AgPOC may represent a useful tool in the hospital setting only if the use is restricted to patients with consistent symptoms less than 4 days old., (© 2021 Wiley Periodicals LLC.)

We report a transfusion-transmitted hepatitis A virus infection in an immunocompromised patient in France, detected shortly after a transfusion of pathogen-reduced pooled platelets. This case raises questions about the efficacy of donor screening methods. Additional safety measures, such as routine donation screening, should be considered.

Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC.

Background: Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance., Materials and Methods: A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm., Results: Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0-0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model., Conclusions: This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hepatitis C virus (HCV) infection is a major cause of severe liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. The HCV burden in public health is estimated at about 71 million people worldwide by World Health Organization (WHO) with at least 400,000 people that died every year from HCV disease [1]. New hepatitis C treatments with oral direct-acting antivirals (DAAs) showing high rates of response, with short treatment duration [2] have been available. HCV can now be eradicated with minimal side effects. Unfortunately, there is no vaccine yet available, but the development of a safe prophylactic vaccine remains a medical priority [3]. For this purpose, Hepatitis B-C subviral envelope particles can be produced by industrialized procedure. It seems to be very promising as this HBV-HCV vaccine candidate has been shown to elicit a broadly cross neutralizing activity against HCV [4]. Despite this revolution in the HCV-treatment, one of major challenge to achieve a global eradication of HCV remains to reduce the under diagnosis. The low rate of diagnosis is a major obstacle in resources limited countries and is mainly due to the cost of molecular tools, that are essential to diagnose and follow chronic HCV infection. In another hand, the mild clinical symptoms observed in HCV chronic disease, may explain that the majority of HCV infected individuals are unaware of their infection, because HCV testing is not generalized, like it is for HIV. HCV was discovered in 1989 after many years of work, by several researchers, who recently obtained the Nobel price [5-7]. This major discovery allowed the description of the HCV genome and later on of the virus replication and cell cycle, and also, importantly, the development of diagnostic tests for the detection of HCV antibodies (Ab) and RNA who were a priority in transfusion. In this review, we will try to get into the virology and cell biology of HCV. Thereafter, we will discuss the different categories of laboratory tests to diagnose/explore HCV infected subjects., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objectives: Hepatitis B and D infections are highly endemic in Mauritania, with prevalences ranging from 10 to 20%. With the present prospective transversal pilot study, we aimed to evaluate the prevalences of HBV, HCV, and HDV infections in healthcare workers (HCWs), and offer treatment or vaccination as required., Methods: At inclusion, each HCW was screened for anti-HBc Ab (followed by HBsAg assay when positive). Additional biological analyses were performed for HBsAg + cases. Depending on the results, HBV vaccination or anti-viral treatment was offered., Results: A total of 3,857 HCWs were included, of whom 1,363 tested negative for anti-HBc Ab and received full vaccination. Of the 2,494 HCWs who were positive for anti-HBc Ab, 1,246 were positive for anti-HBs Ab and 418 were positive for HBsAg. Three HCWs were positive for HBeAg; 66 and 18 had HBV DNA levels respectively > 2,000 and > 20,000 IU/mL; and 48 were positive for anti-HDV Ab among whom 10 were positive for HDV RNA. HCV prevalence was 0.5%. Only seven HCWs fulfilled the criteria for treatment and five of them were treated., Conclusion: Few HCWs in Mauritania are immunised against HBV. The prevalences of anti-HBc Ab and HBsAg observed in this work were similar to those observed in our earlier works, whereas prevalence of active HDV infection was less high. HBV and HDV infections are a serious health concern in Mauritania. New recommendations developed in accordance with WHO guidelines should include mandatory HBV screening and immunisation for HCWs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose., Objectives: The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies., Methods: Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples., Results: Overall sensitivity for IgG was equivalent (around 80 %) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, >14 days after onset of symptoms, was 100.0 % for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98 %) compared to ELISA (95.8 %). Specificity was significantly different between IgA ELISA (78.9 %) and IgM LFIA (95.8 %) (p < 0.05). The best agreement was observed between CLIA and LFIA assays (97 %; k = 0.936)., Conclusion: Excellent sensitivity for IgG detection was obtained >14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The detection and quantification of hepatitis B virus (HBV) DNA from dried blood spots (DBS) is a major tool for chronic hepatitis B management in resource-limited settings. This strategy fits in perfectly with the hepatitis control plan promoted by the World Health Organization. However, few commercial methods are validated for viral load (VL) measurement on DBS., Objectives: Our objective was to evaluate the performance of the HBV VL measurement of the Aptima™ HBV Quant Dx assay on DBS compared to plasma samples on the Panther® platform (Hologic)., Study Design: 266 whole blood samples for routine measurement were included. Five spots of 75 μL of whole blood were loaded onto a card before centrifugation and plasma settling., Results: 149 samples were quantifiable and 117 were not detected. We achieved excellent linearity (r² = 0.994) over a wide range of measurements suitable for clinical practice, and a 95 % lower limit of detection (LLOD-95 %) at 2.65 log 10 IU/mL (445 IU/mL). A good performance of this assay was observed for samples with HBV VL > LLOD-95 % and 100 % of samples were detected if HBV VL was above 2.95 log 10 IU/mL. The correlation between the two matrices for quantitative VLs was good (r² = 0.978) with a very low bias (-0.002 log 10 IU/mL)., Conclusion: The Aptima™ assay can properly detect and quantify HBV DNA in DBS, providing a satisfactory use in clinical monitoring and therapeutic decisions. DBS represents an excellent alternative to plasma, especially in resource-limited countries, while maintaining the performance and advantages of an automated technique., Competing Interests: Declaration of Competing Interest HLGG has received lecture fees from Hologic., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Our laboratory obtained the ISO 15189 accreditation for the plasmatic HIV-1, HBV and HCV viral load (VL) using the m2000 RealTime™ system, which was recently changed for the platform Panther®. Here, we discuss a strategy for performing method validation/verification very quickly. Methods We performed the mandatory (repeatability, internal quality assessment [IQA], measurement uncertainty [MU]) and optional technical verifications for CE/IVD assays using the flexible scope range A. We also performed the mandatory assays for the validation of HIV-1 VL in the cerebrospinal fluid (CSF) using the flexible scope range B. The change was checked by following up on the turnaround time (TAT). Results The coefficient of variation (CV%) for repeatability and IQA complied with the limit of 0.25 log. The MU results ranged from 0.04 to 0.25 log copies or IU/mL. The comparisons of methods showed excellent correlations (R2 = 0.96 for the three parameters) but a delayed centrifugation on HCV VL showed variations of up to 2 log IU/mL. An excellent linearity for HIV-1 in the CSF was obtained from 1.5 to 5 log copies/mL with R2 = 0.99. The TAT increased (84%-98%) in routine usage. Conclusions The three Aptima assays are well suited for routine laboratory use and can be integrated within less than 2 weeks in accordance with flexible scope range A. Our data allows us to confidently perform HIV-1 VL in CSF following flexible scope range B. Finally, we provide an organizational guide for flexible scope management in molecular virology within a short time frame.

Currently, there is a lack of systems for studying the role of hepatitis B viral proteins, such as HBeAg and HBcAg, on liver injury. It is necessary to develop an original tool in order to clarify the role of these viral proteins in hepatic stellate cell activation, and to understand the molecular mechanisms of liver injury. HepaRG are the most reliable hepatocyte-like cells for studying liver functions or disorders. In this paper, we demonstrate that the transduction of differentiated HepaRG (dHepaRG) cells can be performed successfully using lentiviral particles. The production of a functional Green Fluorescent Protein (GFP) assessed by Fluorescence Activated Cell Sorting and fluorescence microscopy is up to 16% of GFP positive cells using a multiplicity of infection (MOI) of 2.4. We demonstrate that this technology can allow the stable expression of GFP during the long lifecycle of the cell (up to four weeks after the cell's passage). With this innovative tool, we aim to express viral proteins such as HBeAg or HBcAg in dHepaRG cells. The preliminary results of this work shows that HBeAg can be efficiently produced in dHepaRG cells and that increased MOI allows a better production of this protein. Our future objective will be to study the role of HBc and HBe proteins on the induction of hepatic fibrosis.

Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice., Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated., Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure., Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients., Patients and Methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology., Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02&#95;AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9)., Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

BACKGROUND Influenza viruses induce uncomplicated infections in most cases in individuals with no known predisposing factors. Acute febrile illness is generally limited to upper respiratory symptoms and several constitutional symptoms, including headache, lethargy, and myalgia. However, influenza A virus is a cause of severe morbidity and mortality worldwide. Some patients are at risk for serious and fatal complications. Cardiac involvement is a well-known condition, but, clinically apparent influenza myocarditis is not common. Few reports exist regarding recurrent fulminant influenza myocarditis. CASE REPORT We report here a fatal case of heart failure following myocarditis in a 14-year-old female who had seasonal flu symptoms but was otherwise healthy. H3N2 influenza virus infection was detected by molecular analyses of throat and nasal swabs, suggesting damage to myocardial cells caused directly by the virus. CONCLUSIONS Pericardial effusion myopericarditis may occur during influenza virus infection in young individuals, even those with no known predisposing factors. Physicians need to be aware that acute myopericarditis can be a fatal complication of recent influenza virus infection in all patients with instable hemodynamics. Early diagnosis and treatment could reduce, in some cases, the risk of severe cardiac events. However, this sudden and fatal outcome was difficult to predict in a healthy young female with no known risk factors.