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1. Mpox Hepatic and Pulmonary Lesions in HIV/Hepatitis B Virus Co-Infected Patient, France

Author: Ruxandra Calin, Claire Périllaud-Dubois, Stéphane Marot, Khaldoun Kerrou, Gilles Peytavin, Marwa Bachir, Anne Laure Kirch, Ludovic Lassel, Vincent Fallet, Joel Gozlan, Jean Baptiste Pain, Patricia Senet, Olivier Ferraris, Sébastien Bine, Mathieu Hubert, Olivier Schwartz, Laurence Morand-Joubert, and Gilles Pialoux
Subjects: mpox, monkeypox virus, HIV, HIV/AIDS and other retroviruses, hepatitis B virus, HBV, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We report a case of persistent disseminated mpox evolving over >6 months in an HIV/hepatitis B virus co-infected patient in France who had
Published: 2024
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2. Correction: COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

Author: Pierre Bay, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Matthieu Turpin, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Damien Roux, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, David Levy, Sonia Burrel, Julien Mayaux, Antoine Kimmoun, Cédric Hartard, Frédéric Pène, Flore Rozenberg, Stéphane Gaudry, Ségolène Brichler, Antoine Guillon, Lynda Handala, Fabienne Tamion, Alice Moisan, Thomas Daix, Sébastien Hantz, Flora Delamaire, Vincent Thibault, Bertrand Souweine, Cecile Henquell, Lucile Picard, Françoise Botterel, Christophe Rodriguez, Armand Mekontso Dessap, Jean-Michel Pawlotsky, Slim Fourati, Nicolas de Prost, and the SEVARVIR investigators
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2024
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3. COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

Author: Pierre Bay, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Matthieu Turpin, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Damien Roux, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, David Levy, Sonia Burrel, Julien Mayaux, Antoine Kimmoun, Cédric Hartard, Frédéric Pène, Flore Rozenberg, Stéphane Gaudry, Ségolène Brichler, Antoine Guillon, Lynda Handala, Fabienne Tamion, Alice Moisan, Thomas Daix, Sébastien Hantz, Flora Delamaire, Vincent Thibault, Bertrand Souweine, Cecile Henquell, Lucile Picard, Françoise Botterel, Christophe Rodriguez, Armand Mekontso Dessap, Jean-Michel Pawlotsky, Slim Fourati, Nicolas de Prost, and the SEVARVIR investigators
Subjects: COVID-19, Invasive pulmonary aspergillosis, Intensive care unit, SARS-CoV-2, Omicron, COVID-19 associated pulmonary aspergillosis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. Methods This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. Results 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. Conclusion This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.
Published: 2024
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4. Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study

Author: Nicolas de Prost, Etienne Audureau, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Pierre Bay, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Guillaume Voiriot, Laurence Morand-Joubert, Sébastien Jochmans, Aurélia Pitsch, Sylvie Meireles, Damien Contou, Amandine Henry, Adrien Joseph, Marie-Laure Chaix, Fabrice Uhel, Diane Descamps, Malo Emery, Claudio Garcia-Sanchez, Charles-Edouard Luyt, Stéphane Marot, Frédéric Pène, Anne-Sophie Lhonneur, Stéphane Gaudry, Ségolène Brichler, Lucile Picard, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati, and the SEVARVIR investigators
Subjects: SARS-CoV-2, Omicron, Sublineage, COVID-19, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. Results The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. Conclusions Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.
Published: 2023
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5. Anti-SARS-CoV-2 Neutralizing Responses in Various Populations: Use of a Rapid Surrogate Lateral Flow Assay and Correlations with Anti-RBD Antibody Levels

Author: Joël Gozlan, Audrey Baron, Anders Boyd, Maud Salmona, Djeneba Fofana, Marine Minier, Audrey Gabassi, Laurence Morand-Joubert, Constance Delaugerre, and Sarah Maylin
Subjects: SARS-CoV-2, neutralizing antibodies, neutralization surrogate assays, Science
Abstract: Background: After the global COVID-19 crisis, understanding post-infectious immunity and vaccine efficacy remains crucial. This study aims to assess anti-SARS-CoV-2 immunity through a quantitative analysis of anti-receptor-binding domain (RBD) antibodies and rapid functional testing of the neutralizing humoral response. Methods: A retrospective analysis was conducted on samples from various cohorts, including partially vaccinated, fully vaccinated, post-COVID/no-vaccination, and post-COVID/vaccination individuals with various immune-competency statuses. The anti-RBD antibodies were measured using an automated chemiluminescence assay, while the neutralizing antibodies’ (NAbs’) activity was assessed through the lateral flow ichroma COVID-19 nAb test (LFT), a surrogate neutralization assay. Results: The analysis revealed various levels of anti-RBD antibodies and seroneutralization responses across cohorts, with the post-COVID/vaccination group demonstrating the most robust protection. A correlation between anti-RBD antibodies and seroneutralization was observed, albeit with varying strength depending on the subgroup analyzed. Longitudinal assessment following natural infection showed an initial surge followed by a decline in both measures. A cutoff of 3.0 log10 BAU/mL was established to predict significant seroneutralization. Conclusions: The ichroma™ COVID-19 nAb test displayed high specificity and emerged as a valuable tool for monitoring anti-SARS-CoV-2 immunity. These findings contribute to understand the antibody response dynamics and underscore the potential of rapid tests in predicting protection against SARS-CoV-2 infection.
Published: 2024
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6. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, and Slim Fourati
Subjects: Science
Abstract: SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.
Published: 2022
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7. Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients

Author: Guillaume Voiriot, Karim Dorgham, Guillaume Bachelot, Anne Fajac, Laurence Morand-Joubert, Christophe Parizot, Grigorios Gerotziafas, Dominique Farabos, Germain Trugnan, Thibaut Eguether, Clarisse Blayau, Michel Djibré, Alexandre Elabbadi, Aude Gibelin, Vincent Labbé, Antoine Parrot, Matthieu Turpin, Jacques Cadranel, Guy Gorochov, Muriel Fartoukh, and Antonin Lamazière
Subjects: Medicine, Science
Abstract: Abstract The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30–4.41] vs. 9.53 [2.56–19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.
Published: 2022
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8. Surging bloodstream infections and antimicrobial resistance during the first wave of COVID–19: a study in a large multihospital institution in the Paris region

Author: Rishma Amarsy, David Trystram, Emmanuelle Cambau, Catherine Monteil, Sandra Fournier, Juliette Oliary, Helga Junot, Pierre Sabatier, Raphaël Porcher, Jérôme Robert, Vincent Jarlier, Guillaume Arlet, Laurence Armand Lefevre, Alexandra Aubry, Laurent Belec, Béatrice Bercot, Stéphane Bonacorsi, Vincent Calvez, Etienne Carbonnelle, Stéphane Chevaliez, Jean-Winoc Decousser, Constance Delaugerre, Diane Descamps, Florence Doucet-Populaire, Jean-Louis Gaillard, Antoine Garbarg- Chenon, Elyanne Gault, Jean-Louis Herrmann, Jérôme Le Goff, Jean-Christophe Lucet, Jean-Luc Mainardi, Anne-Geneviève Marcellin, Laurence Morand-Joubert, Xavier Nassif, Jean-Michel Pawlotsky, Anne-Marie Roque Afonso, Martin Rottman, Christine Rouzioux, Flore Rozenberg, François Simon, Nicolas Veziris, David Skurnik, Jean-Ralph Zahar, Guilene Barnaud, Typhaine Billard Pomares, Gaëlle Cuzon, Dominique Decré, Alexandra Doloy, Jean-Luc Donay, Laurence Drieux-Rouzet, Isabelle Durand, Agnès Ferroni, Vincent Fihman, Nicolas Fortineau, Camille Gomart, Nathalie Grall, Christelle Guillet Caruba, Françoise Jaureguy, Valérie Lalande, Luce Landraud, Véronique Leflon, Patricia Mariani, Liliana Mihaila, Didier Moissenet, Latifa Noussair, Isabelle Podglajen, Isabelle Poilane, Hélène Poupet, Emilie Rondinaud, Valérie Sivadon Tardy, Charlotte Verdet, Emmanuelle Vigier, and Sophie Vimont Billarant
Subjects: COVID-19, Blood culture, Bloodstream infection incidence, Antibiotic consumption, Antimicrobial resistance, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: This study measured the impact of the first wave of COVID-19 pandemic (COVID-19) (March–April 2020) on the incidence of bloodstream infections (BSIs) at Assistance Publique – Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France. Methods: The number of patient admission blood cultures (BCs) collected, number of positive BCs, and antibiotic resistance and consumption were analysed retrospectively for the first quarter of 2020, and also for the first quarter of 2019 for comparison, in 25 APHP hospitals (ca. 14 000 beds). Results: Up to a fourth of patients admitted in March–April 2020 in these hospitals had COVID-19. The BSI rate per 100 admissions increased overall by 24% in March 2020 and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to third-generation cephalosporins (3GC) was also observed in March–April 2020, particularly in K. pneumoniae, enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae...), and P. aeruginosa. A concomitant increase in 3GC consumption occurred. Conclusions: The COVID-19 pandemic had a strong impact on hospital management and also unfavourable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.
Published: 2022
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9. Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Author: Florent Malard, Béatrice Gaugler, Joel Gozlan, Lucie Bouquet, Djeneba Fofana, Lama Siblany, Deborah Eshagh, Olivier Adotevi, Caroline Laheurte, Laure Ricard, Rémy Dulery, Nicolas Stocker, Zoe van de Wyngaert, Alexis Genthon, Anne Banet, Mara Memoli, Souhila Ikhlef, Simona Sestilli, Anne Vekhof, Eolia Brissot, Zora Marjanovic, Yannick Chantran, Nancy Cuervo, Eric Ballot, Laurence Morand-Joubert, and Mohamad Mohty
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p
Published: 2021
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10. Differential Performance of the FilmArray Meningitis/Encephalitis Assay To Detect Bacterial and Viral Pathogens in Both Pediatric and Adult Populations

Author: Aurélie Schnuriger, Sophie Vimont, Alexandre Godmer, Joël Gozlan, Salah Gallah, Muriel Macé, Valérie Lalande, Kenda Saloum, Marine Perrier, Nicolas Veziris, and Laurence Morand-Joubert
Subjects: meningitis/encephalitis, pediatric/adult population, performance, sensitivity/specificity, syndromic assay, Microbiology, QR1-502
Abstract: ABSTRACT Meningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients. IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.
Published: 2022
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11. Environmental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contamination in hospital rooms during the first and third coronavirus disease 2019 (COVID-19) waves

Author: Killian Le Neindre, Jeanne Couturier, Aurélie Schnuriger, Sarah Jolivet, Cyril Gouot, Mickaël Majerholc, Pierre Supplisson, Céline Tan, Marine Perrier, Christelle Lazare, Laurence Morand-Joubert, and Frédéric Barbut
Subjects: Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Abstract: We investigated the frequency, distribution, and risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination around infected patients during the first and third wave of the coronavirus disease 2019 pandemic. The shedding of SARS-CoV-2 in rooms of infected patients was limited in our hospital setting.
Published: 2022
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12. Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children

Author: Djeneba B. Fofana, Houdou Diarra, Ibrahima Guindo, Mahamadou K. Savadogo, Marceline d’Almeida, Fatoumata I. Diallo, Aliou Baldé, Cathia Soulié, Amadou Kone, Anne-Geneviève Marcelin, Almoustapha I. Maiga, Sidonie Lambert-Niclot, Mamoudou Maiga, Sally McFall, Claudia A. Hawkins, Robert L. Murphy, Mariam Sylla, Christine Katlama, Jane L. Holl, Vincent Calvez, and Laurence Morand-Joubert
Subjects: HIV-1, polymorphism, integrase, children, resistance, Africa, Microbiology, QR1-502
Abstract: Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.
Published: 2023
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13. Author Correction: Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, and Slim Fourati
Subjects: Science
Published: 2022
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14. SARS-CoV-2 Neutralizing Responses in Various Populations, at the Time of SARS-CoV-2 Variant Virus Emergence: Evaluation of Two Surrogate Neutralization Assays in Front of Whole Virus Neutralization Test

Author: Stephane Marot, Djeneba Bocar Fofana, Philippe Flandre, Isabelle Malet, Karen Zafilaza, Valentin Leducq, Diane Vivien, Sarah Mrabet, Corentin Poignon, Vincent Calvez, Laurence Morand-Joubert, Anne-Geneviève Marcelin, and Joel Gozlan
Subjects: SARS-CoV-2, COVID-19, neutralizing antibodies, neutralization surrogate assays, SARS-CoV-2 variants, Science
Abstract: The SARS-CoV-2 neutralizing antibodies response is the best indicator of effective protection after infection and/or vaccination, but its evaluation requires tedious cell-based experiments using an infectious virus. We analyzed, in 105 patients with various histories of SARS-CoV-2 infection and/or vaccination, the neutralizing response using a virus neutralization test (VNT) against B.1, Alpha, Beta and Omicron variants, and compared the results with two surrogate assays based on antibody-mediated blockage of the ACE2-RBD interaction (Lateral Flow Boditech and ELISA Genscript). The strongest response was observed for recovered COVID-19 patients receiving one vaccine dose. Naïve patients receiving 2 doses of mRNA vaccine also demonstrate high neutralization titers against B.1, Alpha and Beta variants, but only 34.3% displayed a neutralization activity against the Omicron variant. On the other hand, non-infected patients with half vaccination schedules displayed a weak and inconstant activity against all isolates. Non-vaccinated COVID-19 patients kept a neutralizing activity against B.1 and Alpha up to 12 months after recovery but a decreased activity against Beta and Omicron. Both surrogate assays displayed a good correlation with the VNT. However, an adaptation of the cut-off positivity was necessary, especially for the most resistant Beta and Omicron variants. We validated two simple and reliable surrogate neutralization assays, which may favorably replace cell-based methods, allowing functional analysis on a larger scale.
Published: 2022
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15. SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study

Author: Slim Fourati, Etienne Audureau, Romain Arrestier, Stéphane Marot, Claire Dubois, Guillaume Voiriot, Charles-Edouard Luyt, Tomas Urbina, Julien Mayaux, Anne-Marie Roque-Afonso, Tài Pham, Luce Landraud, Benoit Visseaux, Damien Roux, Raphael Bellaiche, Anne-Sophie L’honneur, Zakaria Ait Hamou, Ségolène Brichler, Stéphane Gaudry, Maud Salmona, Raphaël Clere-Jehl, Elie Azoulay, Laurence Morand-Joubert, Anne-Geneviève Marcelin, Marie-Laure Chaix, Diane Descamps, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, and Nicolas de Prost
Subjects: COVID-19, SARS-CoV-2, variant of concern, acute respiratory failure, intensive care unit, Microbiology, QR1-502
Abstract: The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3–8] vs. 3 [2–4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.
Published: 2022
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16. 'Real life' use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study.

Author: Pierre Gantner, Babacar Sylla, Laurence Morand-Joubert, Pierre Frange, Karine Lacombe, Marie-Aude Khuong, Claudine Duvivier, Odile Launay, Marina Karmochkine, Cédric Arvieux, Amélie Ménard, Lionel Piroth, Ana Canestri, Dominique Trias, Gilles Peytavin, Roland Landman, Jade Ghosn, and Coferal-IMEA048 Study Group
Subjects: Medicine, Science
Abstract: IntroductionLimited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting.MethodsHIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns.ResultsWe included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6.ConclusionsRAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns.
Published: 2019
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17. Combining the Estimated Date of HIV Infection with a Phylogenetic Cluster Study to Better Understand HIV Spread: Application in a Paris Neighbourhood.

Author: Olivier Robineau, Pierre Frange, Francis Barin, Françoise Cazein, Pierre-Marie Girard, Marie-Laure Chaix, Georges Kreplak, Pierre-Yves Boelle, and Laurence Morand-Joubert
Subjects: Medicine, Science
Abstract: To relate socio-demographic and virological information to phylogenetic clustering in HIV infected patients in a limited geographical area and to evaluate the role of recently infected individuals in the spread of HIV.HIV-1 pol sequences from newly diagnosed and treatment-naive patients receiving follow-up between 2008 and 2011 by physicians belonging to a health network in Paris were used to build a phylogenetic tree using neighbour-joining analysis. Time since infection was estimated by immunoassay to define recently infected patients (very early infected presenters, VEP). Data on socio-demographic, clinical and biological features in clustered and non-clustered patients were compared. Chains of infection structure was also analysed.547 patients were included, 49 chains of infection containing 108 (20%) patients were identified by phylogenetic analysis. analysis. Eighty individuals formed pairs and 28 individuals were belonging to larger clusters. The median time between two successive HIV diagnoses in the same chain of infection was 248 days [CI = 176-320]. 34.7% of individuals were considered as VEP, and 27% of them were included in chains of infection. Multivariable analysis showed that belonging to a cluster was more frequent in VEP and those under 30 years old (OR: 3.65, 95 CI 1.49-8.95, p = 0.005 and OR: 2.42, 95% CI 1.05-5.85, p = 0.04 respectively). The prevalence of drug resistance was not associated with belonging to a pair or a cluster. Within chains, VEP were not grouped together more than chance predicted (p = 0.97).Most newly diagnosed patients did not belong to a chain of infection, confirming the importance of undiagnosed or untreated HIV infected individuals in transmission. Furthermore, clusters involving both recently infected individuals and longstanding infected individuals support a substantial role in transmission of the latter before diagnosis.
Published: 2015
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18. Association of residual plasma viremia and intima-media thickness in antiretroviral-treated patients with controlled human immunodeficiency virus infection.

Author: Anders Boyd, Jean-Luc Meynard, Laurence Morand-Joubert, Adrien Michon, Franck Boccara, Jean-Philippe Bastard, Assia Samri, Nabila Haddour, Ziad Mallat, Jacqueline Capeau, Moïse Desvarieux, Pierre-Marie Girard, and Collaboration in HIV, Inflammation and Cardiovascular Disease Study
Subjects: Medicine, Science
Abstract: BackgroundWhile residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences.MethodsThis cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL ResultsNo significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8-10.9), nadir CD4+T-cell (208/mm3, IQR = 143-378), and CD4+T-cell count (555/mm3, IQR = 458-707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements.ConclusionsHigher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.
Published: 2014
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19. Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions.

Author: Guillaume Jacquot, Erwann Le Rouzic, Priscilla Maidou-Peindara, Marion Maizy, Jean-Jacques Lefrère, Vincent Daneluzzi, Carlos M R Monteiro-Filho, Duanping Hong, Vicente Planelles, Laurence Morand-Joubert, and Serge Benichou
Subjects: Medicine, Science
Abstract: Although HIV-1 Vpr displays several functions in vitro, limited information exists concerning their relevance during infection. Here, we characterized Vpr variants isolated from a rapid and a long-term non-progressor (LTNP). Interestingly, vpr alleles isolated from longitudinal samples of the LTNP revealed a dominant sequence that subsequently led to diversity similar to that observed in the progressor patient. Most of primary Vpr proteins accumulated at the nuclear envelope and interacted with host-cell partners of Vpr. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity.
Published: 2009
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20. Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients

Author: Charlotte Charpentier, Sidonie Lambert-Niclot, Marc Wirden, Karine Lacombe, Anne-Geneviève Marcelin, Valentine Marie Ferré, Alexandre Storto, Jade Ghosn, Romain Palich, Christine Katlama, Roland Landman, V Joly, Diane Descamps, Laurence Morand-Joubert, Vincent Calvez, and Cathia Soulié
Subjects: Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Pyridones, Baseline risk, HIV Infections, Drug resistance, Therapy naive, chemistry.chemical_compound, Cabotegravir, Risk Factors, Polymorphism (computer science), Internal medicine, Drug Resistance, Viral, Genotype, Prevalence, medicine, Humans, Pharmacology (medical), Pharmacology, business.industry, Rilpivirine, Infectious Diseases, chemistry, HIV-1, Genotypic resistance, business
Abstract: Background Multivariable baseline factor analysis across cabotegravir + rilpivirine clinical trials showed that HIV-1 subtypes A6/A1 and the presence of rilpivirine resistance-associated mutations (RAMs) were associated with an increased risk of virological failure of this dual therapy. The aim of this study was to describe the prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients. Patients and methods From 2010 to 2020, 4212 sequences from ARV-naive patients were collected from three large Parisian academic hospital genotypic databases. Cabotegravir and rilpivirine RAMs were defined according to the ANRS algorithm. Results Among 4212 ARV-naive patients, 38.6% were infected with subtype B, 32.4% with CRF02_AG (32.4%) and 5.1% with subtype A (85.5% being A6/A1 subtype). Overall, the presence of at least one cabotegravir or rilpivirine RAM was 16.2% and 14.3%, respectively. Considering genotypic resistance interpretation, using the ANRS algorithm, 0.74% (n = 31), 6.2% (n = 261) and 0.09% (n = 4) of sequences were resistant to cabotegravir, rilpivirine or both, respectively. The overall prevalence of L74I in integrase and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade. Thus, adding 183 subtype A6/A1 sequences to 244 sequences interpreted as resistant to rilpivirine led to 427 (10.1%) sequences combining both baseline virological risk factors for cabotegravir + rilpivirine dual-therapy failure. Conclusions Among large sequence databases, when adding prevalence of rilpivirine-resistant viruses and HIV-1 subtype A6/A1 sequences, 10.1% of patients would not be eligible for cabotegravir + rilpivirine dual therapy. These data re-emphasize the need for a pre-therapeutic genotypic resistance test to detect polymorphisms and transmitted drug resistance and to define HIV-1 subtype.
Published: 2021
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21. COVID-19 acute respiratory distress syndrome promotes a specific alternative macrophage polarization

Author: Marc Garnier, Florian Blanchard, Arnaud Mailleux, Laurence Morand-Joubert, Bruno Crestani, and Christophe Quesnel
Subjects: Immunology, Immunology and Allergy
Abstract: Acute respiratory distress syndrome (ARDS) alveolar environment induced a pro-repair anti-inflammatory macrophage polarization. However, patients with coronavirus disease 2019 (COVID-19) ARDS frequently exhibit a huge lung inflammation and present pulmonary scars and fibrosis more frequently than patients with non-COVID-19 ARDS, suggesting that the COVID-19 ARDS alveolar environment may drive a more inflammatory or pro-fibrotic macrophage polarization. This study aimed to determine the effect of the COVID-19 ARDS alveolar environment on macrophage polarization. The main finding was that broncho-alveolar lavage fluids (BALF) from patients with early COVID-19 ARDS drove an alternative anti-inflammatory polarization in normal monocyte-derived macrophages; characterized by increased expressions of CD163 and CD16 mRNA (3.4 [2.7-7.2] and 4.7 [2.6-5.8] fold saline control, respectively - p = 0.02), and a secretory pattern close to that of macrophages stimulated with IL-10, with the specificity of an increased production of IL-6. This particular alternative pattern was specific to early ARDS (compared with late ARDS) and of COVID-19 ARDS (compared with moderate COVID-19). The early COVID-19 ARDS alveolar environment drives an alternative anti-inflammatory macrophage polarization with the specificity of inducing macrophage production of IL-6.
Published: 2022

22. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron, sublineages BA.1, BA.1.1, BA.2 and impact of mutational patterns in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tai Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stephane Gaudry, Segolene Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Jandeaux Louise-Marie, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Christophe Rodriguez, Djillali Annane, Elie Azoulay, Armand Mekontso-Dessap, Jean-Michel Pawlotsky, and Slim Fourati
Abstract: Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with a rarer occurrence of severe disease requiring intensive care. However, a substantial number of patients infected with variant Omicron still experienced severe COVID-19. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 participating intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients for whom SARS-CoV-2 variant lineage was determined, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) was different from that in those infected with variant Delta (n = 111). We observed no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% were immunocompromised, most of whom had received two doses of vaccine or more (85.9%) but displayed a poor humoral response to vaccination (mean difference in serum anti-spike IgG antibody titers between vaccinated and non-vaccinated immunocompromised patients: 1078 BAU/mL [-319.4; 2475.0]; p = 0.160). The mortality rate of immunocompromised patients infected with variant Omicron was significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there was no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms or mutational profile and the 28-day mortality.
Published: 2022
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23. Presentation and outcomes of SARS-CoV-2 Omicron variant infection in haemodialysis patients

Author: Alice Chimon, Elsa Ferrière, Mohamed Ali Lammouchi, Narindra Jouan, Pierre-Antoine Michel, Kenda Saloum, Laurence Morand-Joubert, Aurélie Schnuriger, Marianne Leruez-Ville, Jacques Fourgeaud, Djamal Dahmane, Boutheina Bentaarit, Bruno Guéry, Hafedh Fessi, Hajer Kazdaghli, Farah Sounni, Timothée Fearon, Idris Boudhabhay, Jean-Michel Pawlotsky, Khalil El Karoui, Slim Fourati, and Hamza Sakhi
Subjects: Transplantation, Nephrology
Published: 2022

24. Investigation of healthcare-associated COVID-19 in a large French hospital group by whole-genome sequencing

Author: Valentin Leducq, Jeanne Couturier, Benjamin Granger, Sarah Jolivet, Laurence Morand-Joubert, Jérôme Robert, Michel Denis, Beatrice Salauze, Valérie Goldstein, Karen Zafilaza, Pierre Rufat, Anne-Geneviève Marcelin, Aude Jary, and Frédéric Barbut
Subjects: Cross Infection, SARS-CoV-2, COVID-19, Humans, Microbiology, Delivery of Health Care, Hospitals
Abstract: Despite the quick implementation of infection prevention and control procedures and the use of personal protective equipment within healthcare facilities, many cases of nosocomial COVID-19 transmission have been reported. We aimed to estimate the frequency and impact of healthcare-associated COVID-19 (HA-COVID-19) and evaluate the contribution of whole-genome sequencing (WGS) in cluster investigation.We estimated the frequency and mortality of HA-COVID-19 infections from September 1 to November 30, 2020, with a focus on the evolution of hospitalized community-associated COVID-19 (CA-COVID-19) cases and cases detected among healthcare workers (HCWs) within the Sorbonne University Hospital Group (Paris, France). We thoroughly examined 12 clusters through epidemiological investigations and WGS.Overall, 209 cases of HA-COVID-19 were reported. Evolution of HA-COVID-19 incidence closely correlated with the incidence of CA-COVID-19 and COVID-19 among HCWs. During the study period, 13.9 % of hospitalized patients with COVID-19 were infected in the hospital and the 30-day mortality rate of HA-COVID-19 was 31.5 %. Nosocomial transmission of SARS-CoV-2 led to clusters involving both patients and HCWs. WGS allowed the exclusion of one-third of cases initially assigned to a cluster.WGS analysis combined with comprehensive epidemiological investigations is essential to understand transmission routes and adapt the IPC response to protect both patients and HCWs.
Published: 2022

25. Hepatitis B Virus in West African Children: Systematic Review and Meta-Analysis of HIV and Other Factors Associated with Hepatitis B Infection

Author: Djeneba B. Fofana, Anou M. Somboro, Mamoudou Maiga, Mamadou I. Kampo, Brehima Diakité, Yacouba Cissoko, Sally M. McFall, Claudia A. Hawkins, Almoustapha I. Maiga, Mariam Sylla, Joël Gozlan, Manal H. El-Sayed, Laurence Morand-Joubert, Robert L. Murphy, Mahamadou Diakité, and Jane L. Holl
Subjects: Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health
Abstract: While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger’s test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3–9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.
Published: 2023
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26. Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients

Author: Guillaume Voiriot, Karim Dorgham, Guillaume Bachelot, Anne Fajac, Laurence Morand-Joubert, Christophe Parizot, Grigorios Gerotziafas, Dominique Farabos, Germain Trugnan, Thibaut Eguether, Clarisse Blayau, Michel Djibré, Alexandre Elabbadi, Aude Gibelin, Vincent Labbé, Antoine Parrot, Matthieu Turpin, Jacques Cadranel, Guy Gorochov, Muriel Fartoukh, and Antonin Lamazière
Subjects: Multidisciplinary, SARS-CoV-2, Critical Illness, COVID-19, Humans, Prospective Studies, Bronchoalveolar Lavage Fluid, Biomarkers
Abstract: The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30–4.41] vs. 9.53 [2.56–19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.
Published: 2021

27. Caution in interpretation of SARS-CoV-2 quantification based on RT-PCR cycle threshold value

Author: Kenda Saloum, Aurélie Schnuriger, Yanne Michel, Corinne Amiel, D. B. Fofana, Marine Perrier, Narjis Boukli, Joël Gozlan, Laurence Morand-Joubert, Valérie Marinho, Sidonie Lambert-Niclot, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Microbiology (medical), Oncology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Datasets as Topic, Genome, Viral, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Nasopharynx, medicine, Humans, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, Cycle threshold, business.industry, Diagnostic Tests, Routine, SARS-CoV-2, COVID-19, General Medicine, Viral Load, Infectious Diseases, Real-time polymerase chain reaction, COVID-19 Nucleic Acid Testing, RNA, Viral, Original Article, business, Viral load
Abstract: International audience; RT-PCR is the reference method for diagnosis of a Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. During the setting up of 6 SARS-CoV-2 RT-PCR assays in our laboratory, comparative evaluations were systematically undertaken and allowed to evidence major discrepancies on cycle threshold RT-PCR results between techniques. These tendencies were confirmed in routine application when analyzing sequential samples from the same patients. Our aim was to examine the impact of the technique among factors influencing RT-PCR result, a far surrogate of 'viral load' in the heterogeneous environment of respiratory specimens.
Published: 2021
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28. High seroconversion rate but low antibody titers after two injections of BNT162b2 (Pfizer-BioNTech) vaccine in patients treated by chemotherapy for solid cancers

Author: J. Barrière, Marianne Veyri, P. Maingon, Marc-Antoine Benderra, Romain Palich, J-P. Spano, Z. Adjoutah, Laurence Morand-Joubert, A G Marcelin, Stéphane Marot, Joseph Gligorov, Aurore Vozy, Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Pitié-Salpêtrière], Service d'Oncologie médicale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Cerballiance, HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Service de Virologie [CHU Pitié-Salpêtrière]
Subjects: COVID-19 Vaccines, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, medicine, Humans, In patient, Seroconversion, Letter to the Editor, BNT162 Vaccine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cancer, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Chemotherapy, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, SARS-CoV-2, Vaccination, Antibody titer, COVID-19, Hematology, 3. Good health, mRNA vaccine, Serology, Oncology, 030220 oncology & carcinogenesis, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract: International audience
Published: 2021
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29. The 501Y.V2 SARS-CoV-2 variant has an intermediate viral load between the 501Y.V1 and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients

Author: Elisa Teyssou, Benoit Visseaux, Laurence Morand-Joubert, Vincent Calvez, Cathia Soulié, Aurélie Schnuriger, Charlotte Charpentier, Sidonie Lambert-Niclot, Stéphane Marot, Valentin Leducq, Marc Wirdern, Nadira Houhou-Fidouh, Basma Abdi, Sonia Burrel, Diane Descamps, Sophie Sayon, Anne-Geneviève Marcelin, Aude Jary, Karen Zafilaza, Valentine Marie Ferré, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Laboratoire de virologie [APHP Claude Bernard Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre National de Référence Herpèsvirus [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and TEYSSOU, Elisa
Subjects: Microbiology (medical), Cycle threshold, 2019-20 coronavirus outbreak, variants, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], COVID-19, Newly diagnosed, Biology, Viral Load, Virology, Antibodies, Neutralizing, [SDV] Life Sciences [q-bio], Infectious Diseases, Medicine, Humans, business, Viral load, Letter to the Editor, 501Y.V1, ComputingMilieux_MISCELLANEOUS, 501Y.V2
Abstract: The 501Y.V2 and the 501Y.V1 SARS-CoV-2 variants emerged and spread rapidly into the world. We analysed the viral load of 643 nasopharyngeal samples of COVID-19 patients at diagnosis and found that the 501Y.V1 and the 501Y.V2 variants presented a viral load three to ten times and two times higher than the historical variants, respectively.HighlightsViral load in COVID-19 patient nasopharyngeal samples was different between variants.The 501Y.V2 variant had a viral load 2 times higher than the historical variantsThe 501Y.V2 variant had a viral load slightly lower than the 501Y.V1The 501Y.V1 variant had a viral load 3-10 times higher than the historical variants
Published: 2021
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30. Young people seeking sexual health care but not returning for results

Author: Marion Bonneton, Karine Lacombe, Nga Phuong, Joël Gozlan, Tetiana Kyrychenko, T. Chiarabini, Valérie Lalande, Narjis Boukli, Dominique Decré, Laurence Morand-Joubert, and Nadia Valin
Subjects: medicine.medical_specialty, HBsAg, Chlamydia, Adolescent, business.industry, Sexual Behavior, Attendance, virus diseases, HIV Infections, Dermatology, Hepatitis B, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, Serology, Men who have sex with men, Infectious Diseases, Family medicine, HIV Seropositivity, Epidemiology, medicine, Humans, Sexual Health, business, Reproductive health
Abstract: The control of STIs among adolescents is a recognised health priority in France.1 There are limited data on STI epidemiology among adolescents both across Europe and at the global level.2–4 We report a cross-sectional study to describe the cascade of care (number tested, diagnosed, treated) for youngsters (≤18 years) attending Free HIV and STI Information, Screening and Diagnosis Clinics (CeGIDD) in Paris for consultation on STIs. HIV, serology or rapid test, anti-HCV, HBsAg, anti-HBcorAb, Chlamydia, Gonococci and Mycoplasma specimens for PCR were collected as part of the routine approach at STI diagnosis. Syphilis serology was performed only in patients with more than 10 partners each year, migrants and men who have sex with men. CeGIDD was totally free of charge. The interval between first attendance and availability of test results was up to 7 days. Patients …
Published: 2021
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31. Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients

Author: Agnès Carol, Narjis Boukli, Elyanne Gault, Juliette Villemonteix, Tiffany Guilleminot, Héloïse Petit, Guislaine Carcelain, Dominique Challine, Diane Descamps, Sarah Maylin, Jean-François Meritet, Claire Périllaud-Dubois, Laurence Morand-Joubert, Sonia Burrel, Marie-Anne Rameix-Welti, Frédérique Moreau, Charlotte Charpentier, Jérôme LeGoff, Jean-Michel Pawlotsky, Anne-Geneviève Marcelin, Emmanuel Gordien, Christelle Vauloup-Fellous, Samuel Lepape, Isabelle Podglajen, Slim Fourati, Sepideh Akhavan, Nadhira Houhou-Fidouh, Ana-Maria Roque-Afonso, Marianne Leruez-Ville, Vincent Mackiewicz, Florence Damond, Véronique Avettand-Fenoel, Jacques Fourgeaud, Jean-Baptiste Ronat, Chakib Alloui, Ségolène Brichler, Joël Gozlan, Thierry Naas, Elise Gardiennet, Marie-Laure Chaix, Stéphane Bonacorsi, Constance Delaugerre, Flore Rozenberg, Laurent Dortet, Stéphane Marot, Service de Virologie [Hôpital Paul-Brousse - APHP] (World Health Organization Rubella National Reference Laboratory), Hôpital Paul Brousse, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Microbiologie Clinique [Hôpital Avicenne - APHP], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Microbiologie et Hygiène [AP-HP Hôpital Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Microbiologie [Hôpital Robert Debré - APHP], Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Comets, Emmanuelle, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Microbiology (medical), 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Antibodies, Viral, Sensitivity and Specificity, COVID-19 Serological Testing, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Immunoassay, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], business.industry, SARS-CoV-2, Brief Report, COVID-19, General Medicine, Report evaluation, Serum samples, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Immunoglobulin M, Reagent Kits, Diagnostic, business
Abstract: We report evaluation of 30 assays’ (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04232-3.
Published: 2021
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32. The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients

Author: Emna Ghidaoui, Stéphane Marot, Sidonie Lambert-Niclot, Basma Abdi, David Boutolleau, Héloise Delagrèverie, Charlotte Charpentier, Elisa Teyssou, Ségolène Brichler, Aude Jary, Laurence Morand-Joubert, Diane Descamps, Vincent Calvez, Anne-Geneviève Marcelin, Cathia Soulié, Sepideh Akhavan, Aurélie Schnuriger, Valentine Marie Ferré, Eve Todesco, Nadhira Houhou-Fidouh, Benoit Visseaux, TEYSSOU, Elisa, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Strasbourg, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Avicenne [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de virologie [APHP Claude Bernard Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Herpèsvirus [CHU Pitié Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Microbiology (medical), Delta, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Alpha (ethology), Newly diagnosed, Biology, Nasopharynx, Humans, Beta (finance), Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Alpha, SARS-CoV-2, Variants, Beta, COVID-19, Viral Load, Virology, United Kingdom, [SDV] Life Sciences [q-bio], Infectious Diseases, Spike Glycoprotein, Coronavirus, Viral load
Abstract: International audience; The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients
Published: 2021
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33. Presence of HIV-1 G-to-A mutations linked to APOBEC editing is more prevalent in non-B HIV-1 subtypes and is associated with lower HIV-1 reservoir

Author: Romain Palich, Marc Wirden, Sidonie Lambert-Niclot, Anne Simon, Marc-Antoine Valantin, Laurence Morand-Joubert, Sophie Sayon, Anne-Geneviève Marcelin, Elisa Teyssou, Basma Abdi, Christine Katlama, Vincent Calvez, Cathia Soulié, Roland Tubiana, Aude Jary, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], HAL-SU, Gestionnaire, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de virologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Microbiology (medical), APOBEC, Male, 030106 microbiology, terminator, HIV Infections, Biology, medicine.disease_cause, viral load result, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, HIV DNA, Proviruses, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, APOBEC Deaminases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pharmacology, Mutation, DNA synthesis, HIV, DNA, Viral Load, Virology, Stop codon, 3. Good health, genotype HIV-1, Infectious Diseases, Terminator (genetics), chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV-1, codon, Viral load
Abstract: Objectives APOBEC3 editing activity contributes to sequences variation and viral diversification. We aimed to characterize virological and clinical factors associated with G-to-A mutations and stop codons in the HIV-1 reservoir, markers of APOBEC3 footprints, in order to better understand HIV-1 diversity among virologically suppressed HIV-1-infected patients. Methods Immuno-virological and clinical factors were compared between 92 patients harbouring G-to-A mutations and stop codons (APOBEC+) in the reverse transcriptase gene and 92 patients without G-to-A mutations (APOBEC–) and stop codons in their DNA genotypes. Results Patients were predominantly men (74.5%) and were mostly infected by B-subtype (69.0%), with 44.1% and 55.9% in APOBEC+ and APOBEC– groups, respectively. At time of HIV DNA genotypes, the total cell-associated HIV-1 DNA load was 2.34 log10 copies/106 cells (IQR 1.85–2.67) and 33.2% of them had a detectable ultrasensitive plasma viral load. Hypermutated sequences were identified in 28.2% of the APOBEC+ group. The median total cell-associated HIV-1 DNA level was significantly lower in APOBEC+ than APOBEC– group: 2.13 log10 copies/106 cells (IQR 1.60–2.60) versus 2.52 log10 copies/106 cells (IQR 2.19–2.71) (P Conclusions These results show an independent association between the presence of G-to-A mutations and stop codons with HIV-1 subtype non-B and low proviral DNA that could be explained by the APOBEC3 footprints and restriction of DNA synthesis and integration. However, further investigations are needed to study the contribution of Vif amino acid variability among HIV-1 subtypes.
Published: 2021
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34. High Incidence of False-Positive Results in Patients with Acute Infections Other than COVID-19 by the Liaison SARS-CoV-2 Commercial Chemiluminescent Microparticle Immunoassay for Detection of IgG Anti-SARS-CoV-2 Antibodies

Author: Joël Gozlan, Nancy Stella Cuervo, Aurélie Schnuriger, Narjis Boukli, Laurence Morand-Joubert, Melchior Le Mene, and Cécilia Laroche
Subjects: serological tests, 0301 basic medicine, Microbiology (medical), viruses, 030106 microbiology, coronavirus, Disease, medicine.disease_cause, Serology, 03 medical and health sciences, 0302 clinical medicine, Immune system, antibodies, Medicine, 030212 general & internal medicine, skin and connective tissue diseases, Letter to the Editor, Coronavirus, biology, medicine.diagnostic_test, Liaison, SARS-CoV-2, business.industry, fungi, COVID-19, virus diseases, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Virology, Immunoassay, biology.protein, Antibody, business, Betacoronavirus
Abstract: Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major pandemic ([1][1]). Diagnosis is based on detection of viral RNA, whereas the immune response to SARS-CoV-2 is measured by serological tests which detect antibodies (Abs) directed
Published: 2020
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35. Broad-based SARS-CoV-2 testing program for healthcare workers in a primary care hospital in France

Author: Gilles Pialoux, Michel Denis, Martin Siguier, Marine Nadal, Julie Chas, Laurence Morand-Joubert, and Anne Fajac
Subjects: myalgia, Adult, Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Paris, Adolescent, Fever, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Anosmia, Health Personnel, Chest ct, Primary care, Health personnel, Young Adult, COVID-19 Testing, Risk Factors, Health care, medicine, Infection control, Humans, Aged, Infection Control, Primary Health Care, business.industry, SARS-CoV-2, virus diseases, COVID-19, Myalgia, Middle Aged, Hospitals, body regions, Infectious Diseases, Emergency medicine, Female, France, medicine.symptom, business, Ageusia
Abstract: A broad-based SARS-CoV-2 testing program for all symptomatic healthcare workers (HCWs) was implemented in Tenon hospital, Paris, France. From February 26 to April 22, 2020, 701 symptomatic HCWs were screened, of whom 247 (35.2%) tested positive for SARS-Cov-2. Myalgia, fever, anosmia and ageusia were associated with RT-PCR positivity. Testing of HCWs is an essential step toward control of the epidemic. Further studies could establish clinical algorithms for SARS-CoV-2 diagnosis to compensate for RT-PCR test and chest CT limits or unavailability.
Published: 2020

36. Prevalence and clinical impact of minority resistant variants in patients failing an integrase inhibitor-based regimen by ultra-deep sequencing

Author: Eve Todesco, Maxime Grude, Sidonie Lambert-Niclot, A G Marcelin, Nathalie Désiré, Diane Descamps, Gilles Peytavin, Minh Patrick Lê, Christine Katlama, Philippe Flandre, Charlotte Charpentier, Thuy Van Nguyen, Marc Wirden, D. B. Fofana, Laurence Morand-Joubert, Vincent Calvez, Gestionnaire, Hal Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), Paris, medicine.medical_specialty, Genotyping Techniques, [SDV]Life Sciences [q-bio], 030106 microbiology, Integrase inhibitor, HIV Infections, Drug resistance, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, Antiretroviral Therapy, Highly Active, Internal medicine, Drug Resistance, Viral, Prevalence, medicine, Humans, Pharmacology (medical), HIV Integrase Inhibitors, Treatment Failure, Pharmacology, Sanger sequencing, Elvitegravir, business.industry, High-Throughput Nucleotide Sequencing, Middle Aged, Raltegravir, Resistance mutation, [SDV] Life Sciences [q-bio], Regimen, Infectious Diseases, chemistry, Dolutegravir, HIV-1, symbols, Female, business, medicine.drug
Abstract: Background Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients. Objectives This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen. Methods Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS). Baseline samples of patients with virological failure (VF) (n = 34) and of those with virological success (VS) (n = 31) under INSTI treatment were sequenced by UDS. Data were analysed using the SmartGene platform, and resistance was interpreted according to the ANRS algorithm version 27. Results At failure, the prevalence of at least one INSTI-resistant variant was 39.6% by Sanger sequencing and 57.5% by UDS, changing the interpretation of resistance in 17/134 (13%) patients. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). There was no difference in prevalence of baseline MiRVs between patients with VF and those with VS. MiRVs found at baseline in patients with VF were not detected at failure either in majority or minority mutations. Conclusions UDS is more sensitive than Sanger sequencing at detecting INSTI MiRVs at treatment failure. The presence of MiRVs at failure could be important to the decision to switch to other INSTIs. However, there was no association between the presence of baseline MiRVs and the response to INSTI-based therapies in our study.
Published: 2018
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37. P-149: Immunogenicity of SARS-CoV-2 vaccine in patients with multiple myeloma

Author: D. B. Fofana, Souhila Ikhlef, Florent Malard, Zoé Van de Wyngaert, Lucie Bouquet, Béatrice Gaugier, Mohamad Mohty, Zora Marjanovitch, Laurence Morand-Joubert, and Joël Gozlan
Subjects: Cancer Research, medicine.medical_specialty, biology, business.industry, Immunogenicity, ELISPOT, Hematology, medicine.disease, Gastroenterology, Poster Presentations, Vaccination, Transplantation, Oncology, Internal medicine, medicine, biology.protein, Seroconversion, Antibody, business, Adverse effect, Multiple myeloma
Abstract: We evaluated the safety and immunogenicity of the BNT162b2 vaccine in 52 patients with multiple myeloma (MM). Median age was 71.3 (range, 39.6-90.8) years. 26 (50%) patients had received active treatment including an immunomodulatory drug (IMiD) (n=21), an anti-CD38 monoclonal antibody (n=11) and/or a proteasome inhibitor (n=4). 21 had received previous treatment interrupted at a median of 27.5 (range, 3.5-169.3) months before first vaccine inoculum. 5 patients had indolent untreated MM. 35 patients had a history of autologous hematopoietic cell transplantation (HSCT) performed at a median of 44.4 (range, 3.5-169.3) months before first vaccine inoculum. The vaccination was well tolerated with few non-severe adverse events. Immune efficacy evaluated by antibody seroconversion showed a significant increase of anti-Spike (S) IgG antibodies between day (d)28 and d42 (p= 3100 UA/mL). We found that patients’ age (>=71 years versus 25 versus = 120/L) had no impact on achievement of a protective anti-S IgG level after two BNT162b2 inocula. In contrast, male gender, and ongoing chemotherapy were associated with a significantly decreased probability of achieving the defined protective anti-S IgG level after two BNT162b2 inocula [odds ratio (OR) 0.126, 95% confidence interval (95% CI) 0.022-0.709, p=0.02; OR 0.146, 95%CI 0.025-0.866, p=0.03, respectively]. Finally, using the IFN-g ELISPOT assay in 12 patients, we found a significant increase in T cell response in 12 MM patients against the S protein, with 7 patients (58%) having an anti-S IgG positive ELISPOT after the second BNT162b2 inoculum. Conclusion These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with MM, but only around half of the patients are likely to achieve effective immune protection against COVID-19.
Published: 2021
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38. Sensitivity of the STAT-VIEW rapid self-test and implications for use during acute HIV infection

Author: Laurence Morand-Joubert, Anders Boyd, Narjis Boukli, Pierre-Marie Girard, Julie Bottero, and Noémie Wendremaire
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Point-of-care testing, Blotting, Western, HIV Infections, Dermatology, HIV Antibodies, Logistic regression, Sensitivity and Specificity, Chromatography, Affinity, Serology, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Mass Screening, 030212 general & internal medicine, Stage (cooking), Mass screening, Retrospective Studies, Immunoassay, Acute HIV infection, Transmission (medicine), business.industry, Retrospective cohort study, Middle Aged, 030104 developmental biology, Infectious Diseases, Point-of-Care Testing, Acute Disease, Immunology, HIV-1, RNA, Viral, Female, France, business
Abstract: ObjectivesHIV testing is an important step towards diminishing incident infections. Rapid self-tests whose use is becoming more common in France could help increase access to testing, yet could fail to diagnose HIV during acute HIV infection (AHI). The aim of the present study was to evaluate HIV-detection sensitivity of a commonly used rapid self-test (STAT-VIEW HIV1/2), compared with another point-of-care rapid test (INSTI), among patients presenting with AHI.MethodsIndividuals tested at Saint-Antoine Hospital (Paris, France) with negative or indeterminate western blot (WB) results and detectable HIV-RNA were included. Rapid tests were performed retrospectively on stored serum. Patients with and without reactive rapid tests were compared, while probability of having a reactive test was modelled across infection duration using logistic regression.ResultsOf the 40 patients with AHI, 23 (57.5%) had a reactive STAT-VIEW rapid test. Patients with non-reactive versus reactive tests had a significantly shorter median time since infection (p=0.01), time since onset of symptoms (p=0.009), higher proportion with Fiebig stage III versus IV (p=0.003), negative WB results (p=0.007), higher HIV-RNA levels (p=0.001) and lower CD4+ and CD8+ cell count (p=0.03, pConclusionsOver half of AHI patients had reactive serology using the STAT-VIEW rapid self-test when performed on serum samples. Considering that detection sensitivity increased substantially over infection time, individuals should not rely on a negative result to accurately exclude HIV infection within at least 5 weeks of potential HIV exposure. Notwithstanding strong recommendations against rapid test use during AHI, some utility in detecting HIV is observed 5–12 weeks after transmission.
Published: 2017
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39. Evaluation of 31 Commercial SARS-CoV-2 Serology Assays

Author: Florence Damond, Fourati S, Charlotte Charpentier, Tiffany Guilleminot, Carol A, Alloui A, Samuel Le Pape, Baudier Mc, Jacques Fourgeaud, Héloïse Petit, Isabelle Podglajen, A G Marcelin, Marianne Leruez-Ville, Marot Ss, Stéphane Bonacorsi, Sepideh Akhavan, Laurent Dortet, Flore Rozenberg, Mackiewicz, Rona J, Elyanne Gault, Joël Gozlan, Thierry Naas, Gordien N, Fellous Cv, Guislaine Carcelain, François Moreau, Sarah Maylin, Ségolène Brichler, Constance Delaugerre, Laurence Morand-Joubert, Fenoel Va, Juliette Villemonteix, Boukli-Hacene N, Sonia Burrel, Elise Gardiennet, Afonso Ar, Pawlotsky Jm, Dubois C, Dominique Challine, Welti Mr, Jérôme Le Goff, Diane Descamps, Jean-François Meritet, and Houhou N
Subjects: medicine.medical_specialty, biology, business.industry, Gold standard (test), medicine.disease, Roche Diagnostics, biology.organism_classification, Abbott Diagnostics, Rubella, Serology, Informed consent, Internal medicine, Pandemic, Medicine, business, Sida
Abstract: Background: The virus responsible of severe acute respiratory syndrome named SARS-CoV-2 and causing the new coronavirus disease (COVID-19) has gone global within three months. The current gold standard technique used to detect SARS-CoV-2 is real-time reverse transcription-polymerase chain reaction (rRT-PCR) from naso-pharyngeal swabs but it may be negative in up to 30% of COVID-19 patients. Detection of specific antibodies against SARS-CoV-2 may therefore enhance sensitivity of the current biological diagnosis, as well as monitor the extent of the epidemics in global or specific population, such as health-care worker. Many serological assays are currently available, but their clinical performances are still to be evaluated. Material and Method: A total of 2,594 serum samples collected from patients with SARS-CoV-2 infection documented by a positive rRT-PCR were enrolled in this study. They were tested for IgM/IgG/IgA against SARS-CoV-2 using 31 commercial assays. Antibody response was assessed depending on the onset of symptoms. In addition, 1,996 pre-epidemic serum samples expected to be negative were tested to assess specificity. Results: Rapid tests for qualitative detection of anti-SARS-CoV-2 antibodies (RDTs) achieved 77.4-100%, and ELISA/CLIA (ELISA) assays 58.8-100% for SARS-CoV-2-specific total antibodies (TAb) specificity. From 15 days after onset of symptoms, 13/18 RDT and 8/13 ELISA reached sensitivity > 90%. However, only 4 RDT and 3 ELISA assays fitted both sensitivity (> 90%) and specificity (> 98%) criteria according to French recommendations. Conclusions: Serology may offer valuable information during the course of COVID-19 pandemic, at the condition that commercial assays give reliable results. Contrasted performances were observed among the 31 commercial assays we evaluated, which underlines the importance of independent evaluation before clinical implementation. Funding Statement: This study was funded by the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS, AC43)". Declaration of Interests: JM Pawlotsky has served as an advisor and/or a speaker for Abbvie, Gilead, GlaxoSmithKline, Merck, Regulus and Siemens Healthcare. C Vauloup-Fellous served as un expert (rubella and CMV serology) for Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare and DiaSorin. No other authors have any competing interests to declare. Ethics Approval Statement: The study was carried out in accordance with the Declaration of Helsinki. This work was a retrospective non-interventional study with no addition to standard care procedures. Reclassification of biological remnants into research material after completion of the ordered virological tests was approved by the local interventional review board of hospital. According to the French Public Health Code (CSP Article L.1121-1.1) such protocols are exempted from individual informed consent.
Published: 2020
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40. Evaluation of a rapid diagnostic assay for detection of SARS CoV-2 antigen in nasopharyngeal swab

Author: Alexis Cuffel, Laurence Morand-Joubert, Christelle Vauloup-Fellous, A.-M. Roque-Afonso, Sidonie Lambert-Niclot, Jérôme Le Goff, Samuel Le Pape, Constance Delaugerre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), and Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Microbiology (medical), viruses, Point-of-care testing, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, rapid diagnostic test, Virus, 03 medical and health sciences, 0302 clinical medicine, antigen, Antigen, Pandemic, medicine, 030212 general & internal medicine, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Rapid diagnostic test, medicine.diagnostic_test, biology, business.industry, Special Issue, SARS-CoV-2, virus diseases, biology.organism_classification, Virology, 3. Good health, Immunoassay, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business, Betacoronavirus
Abstract: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus causing causing Coronavirus disease 2019 (COVID-19) was reported for the first time in Wuhan (Hubei, China) in December 2019 (1, 2) and has become a major public health concern all over the world.…
Published: 2020
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41. Variability of the HIV-1 3′ polypurine tract (3′PPT) region and implication in integrase inhibitor resistance

Author: Laurence Morand-Joubert, Olivier Delelis, Isabelle Malet, Valentin Leducq, Anne-Geneviève Marcelin, Vincent Calvez, B. Abdi, Thuy Van Nguyen, Laboratoire de biologie et pharmacologie appliquée (LBPA), and Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)
Subjects: Microbiology (medical), Genotype, Sequence analysis, [SDV]Life Sciences [q-bio], Integrase inhibitor, HIV Infections, Context (language use), HIV Integrase, Drug resistance, Virus Replication, medicine.disease_cause, Viral Proteins, 03 medical and health sciences, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), HIV Integrase Inhibitors, Treatment Failure, Gene, Retrospective Studies, 030304 developmental biology, Pharmacology, 0303 health sciences, Mutation, Base Sequence, biology, 030306 microbiology, Reverse Transcription, Sequence Analysis, DNA, Virology, Reverse transcriptase, 3. Good health, Integrase, Infectious Diseases, Purines, HIV-1, biology.protein
Abstract: Background Integrase strand-transfer inhibitors (INSTIs) are efficient at impairing retroviral integration, which is a critical step in HIV-1 replication. To date, resistance to these compounds has been explained by mutations in the viral protein integrase, which catalyses the integration step. Recently, it has been shown that selected mutations in the 3′ polypurine tract (3′PPT), a sequence involved in the reverse transcription mechanism, result in high-level resistance to these compounds. This observation was reinforced by the description of a patient who failed INSTI treatment by selecting mutations in the 3′PPT sequence. Methods Sequences of the 3′PPT region were analysed in 30706 treatment-naive patients from the public Los Alamos database belonging to six different subtypes and, in parallel, in 107 patients failing INSTI treatment. Results The analysis showed that the sequences of patients failing INSTI treatment, in the same way as those of treatment-naive patients, are very well conserved regardless of the presence or absence of resistance mutations in the integrase gene. Conclusions This study confirms that the selection of a mutation in the 3′PPT region conferring high-level resistance to INSTIs is a rare event. It would require a particular in vivo context and especially a long enough time to be selected, this exposure time being generally reduced by the rapid change of treatment in the case of virological failure. Larger-scale studies in patients with INSTI treatment failure are needed to determine whether the 3′PPT region can play an important role in vivo in INSTI resistance.
Published: 2019
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42. INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

Author: Christine Katlama, Sidonie Lambert-Niclot, Marc Wirden, Laurence Morand-Joubert, Romain Palich, D. B. Fofana, Anders Boyd, Vincent Calvez, Rachid Agher, Jean-Luc Meynard, Pierre-Marie Girard, Nadia Valin, Anne-Geneviève Marcelin, Marc-Antoine Valantin, Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
Subjects: 0301 basic medicine, initiation antiretroviral therapy, medicine.medical_specialty, 030106 microbiology, Integrase inhibitor, Viremia, Gastroenterology, Major Articles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interquartile range, Internal medicine, medicine, Hiv infected patients, Protease inhibitor (pharmacology), 030212 general & internal medicine, business.industry, integrase inhibitor, HIV, medicine.disease, Reverse transcriptase, 3. Good health, residual viremia, Infectious Diseases, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Viral load, CD8
Abstract: Background During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear. Methods HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA >200 copies/mL at ART initiation and achieved a VL 200 copies/mL or 2 VL > 50 copies/mL) while accounting for frequency of VL measurements. Results Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3–4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P < .001), female gender (P = .04), lower baseline VL (P < .001), baseline CD4+ >500 vs Conclusions VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution.
Published: 2019
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43. Prévalence des infections à virus respiratoires en période épidémique de SARS-CoV-2 : comment une épidémie en chasse une autre

Author: Aurélie Schnuriger, Nadia Valin, Karine Lacombe, J. Jullien, Patrick Ingiliz, K. Boussaid, Joël Gozlan, M. Sukach, Laurence Morand-Joubert, and T. Chiarabini
Subjects: Gynecology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Infectious Diseases, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, business, Article
Abstract: Introduction Le 10 mars 2020, l’OMS a déclaré pandémique la diffusion du SARS-CoV2 en recommandant de pratiquer de façon massive le dépistage du virus. Cette épidémie s’est installée alors que les épidémies hivernales de virus respiratoires n’étaient pas encore achevées. Afin de mieux comprendre les étiologies des syndromes grippaux en période COVID-19, nous avons analysé les prélèvements effectués dans un centre de dépistage hospitalier Francilien au tout début de l’épidémie. Matériels et méthodes La période d’étude s’est étendue du 28 février au 27 mars 2020. Tout patient consultant pour une recherche de SARS-CoV2 par RT-PCR dans le cadre d’un syndrome grippal a bénéficié d’une PCR multiplex pour les autres virus respiratoires. Les caractéristiques démographiques, cliniques et virologiques des consultants ont été analysées et les variables associées aux prélèvements positifs pour le SARS-CoV ou les autres virus ont été recherchées par régression logistique. Résultats Au total 707 patients ont consulté pendant la période d’étude et 468 patients ont bénéficié de la recherche de SARS-CoV2 et autres virus respiratoires. L’âge médian (IQR) était de 37 ans (29–50) avec 139 hommes (29,7 %). La prévalence du SARS-CoV2 était de 37,4 % (IQR : 33,01–41,8), et 37 sujets (7,9 %) étaient positifs pour d’autres pathogènes : Influenza A – 6 (1,3 %), Influenza B – 7 (1,5 %), Metapneumovirus – 5 (1,1 %), Rhinovirus – 4 (0,9 %), Coronavirus (229E, HKU1) – 3 (0,6 %), Adenovirus – 2 (0,4 %), Enterovirus – 4 (0,9 %), M. pneumoniae – 1 (0,2 %), Virus Respiratoire syncytial – 1 (0,2 %), infection mixte hors SARS-CoV-2 – 4 (0,9 %). À noter qu’aucun agent pathogène n’a été retrouvé chez 256 consultants. Les symptômes d’anosmie, fièvre et céphalées étaient plus fréquemment présents chez les sujets avec SARS-CoV2 comparés aux autres pathogènes (respectivement 26,3 % vs 2,7 %, p
Published: 2020

44. 'Real life' use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study

Author: Claudine Duvivier, Jade Ghosn, Dominique Trias, Laurence Morand-Joubert, Odile Launay, Pierre Frange, Babacar Sylla, Amélie Menard, Ana Canestri, Marina Karmochkine, Marie-Aude Khuong, Cédric Arvieux, Lionel Piroth, Pierre Gantner, Gilles Peytavin, Karine Lacombe, Roland Landman, Laboratoire de Virologie [Strasbourg], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre d'infectiologie Necker-Pasteur [CHU Necker], Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Pontchaillou [Rennes], Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses et Tropicales [CHU Tenon], CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Tenon [AP-HP], MSD France, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), The study was funded by a grant from Merck Sharp Dohme France., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Service des maladies infectieuses et tropicales [CHU Tenon], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, animal structures, Science, Human immunodeficiency virus (HIV), medicine.disease_cause, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Obstetrics and gynaecology, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Raltegravir Potassium, Humans, Medicine, 030212 general & internal medicine, Adverse effect, Multidisciplinary, business.industry, Obstetrics, Pregnancy Outcome, medicine.disease, Raltegravir, 030112 virology, 3. Good health, Treatment Outcome, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, RNA, Viral, Gestation, Female, France, business, Research Article, Cohort study, medicine.drug
Abstract: IntroductionLimited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting.MethodsHIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns.ResultsWe included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6.ConclusionsRAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns.
Published: 2019
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45. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France

Author: Gilles Peytavin, Mary-Anne Trabaud, Anne Signori-Schmuck, Charlotte Charpentier, Marc Wirden, Cécile Henquell, Laurence Bocket, Catherine Delamare, Samira Fafi-Kremer, Jacques Izopet, Chakib Allaoui, Georges Dos Santos, A. Beby-Defaux, Benoit Visseaux, Virginie Ferré, Coralie Pallier, Diane Descamps, Stéphanie Marque-Juillet, Lambert Assoumou, Magali Bouvier-Alias, Sophie Vallet, Alexis de Rougemont, Hélène Le Guillou-Guillemette, Vincent Calvez, Stéphanie Raymond, Corinne Amiel, Honorine Fenaux, Anne De Monte, Francis Barin, Anne Krivine, Véronique Avettand-Fenoel, Annick Allardet-Servent, Jean-Christophe Plantier, Rachid Ait-Namane, Laurence Morand-Joubert, Marie-Laure Chaix, Camille Tumiotto, Maxime Grude, Anne Maillard, Laurence Courdavault, Brigitte Montes, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Avicenne [AP-HP], CHU Clermont-Ferrand, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de la Martinique [Fort de France], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Victor Dupouy, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Mzembaba, Sandy, Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Argenteuil (CH Argenteuil), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Paris Descartes, Sorbonne Paris Cité, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Normandie Université (NU)-Normandie Université (NU), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and ANRS – France REcherche Nord&Sud Sida-hiv Hépatites
Subjects: 0301 basic medicine, Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], Integrase inhibitor, hiv, HIV Infections, Drug resistance, MESH: HIV-1 / genetics, MESH: Genotype, MESH: HIV Infections / epidemiology, 0302 clinical medicine, Genotype, Blood plasma, HIV Seropositivity, rna-directed dna polymerase, Prevalence, rna, Pharmacology (medical), 030212 general & internal medicine, MESH: Chronic Disease / epidemiology, ComputingMilieux_MISCELLANEOUS, cd4 count determination procedure, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, anti-retroviral agents, MESH: France / epidemiology, Antiinfective agent, MESH: Middle Aged, Incidence (epidemiology), Middle Aged, MESH: Drug Resistance, Viral / genetics, 3. Good health, endopeptidases, [SDV] Life Sciences [q-bio], integrase inhibitors, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: RNA, Viral / blood, Female, France, MESH: HIV Seropositivity / epidemiology, Microbiology (medical), Adult, medicine.medical_specialty, peptide hydrolases, MESH: Mutation, Anti-HIV Agents, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / classification, MESH: HIV-1 / drug effects, Virus, MESH: HIV Infections / transmission, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Humans, viruses, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, plasma, safe sex, MESH: Prevalence, Pharmacology, drug resistance, MESH: Humans, business.industry, MESH: Adult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, CD4 Lymphocyte Count, MESH: Anti-HIV Agents / therapeutic use, Chronic Disease, Mutation, HIV-1, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; 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_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.
Published: 2018
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46. Resistance profile and treatment outcomes in HIV-infected children at virological failure in Benin, West Africa

Author: Laurence Morand-Joubert, D. B. Fofana, M d'Almeida, Gilles Peytavin, R K Keke, Sidonie Lambert-Niclot, A G Marcelin, B Lafia, L Zohoun-Guidigbi, Cathia Soulié, P M Girard, Gestionnaire, Hal Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre National Hospitalier Universitaire Hubert K. Maga de Cotonou (CNHU-HKM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Programme Santé de Lutte contre le Sida (PSLS), Cotonou, Bénin, Service de Virologie [CHU Pitié-Salpêtrière], and CHU Pitié-Salpêtrière [AP-HP]
Subjects: 0301 basic medicine, Microbiology (medical), Male, Pediatrics, medicine.medical_specialty, Adolescent, Genotyping Techniques, Anti-HIV Agents, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, Integrase inhibitor, HIV Infections, Drug resistance, Virus Replication, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, medicine, Benin, Humans, Pharmacology (medical), Treatment Failure, education, Child, Genotyping, Pharmacology, education.field_of_study, business.industry, virus diseases, Viral Load, medicine.disease, CD4 Lymphocyte Count, [SDV] Life Sciences [q-bio], Regimen, Africa, Western, Infectious Diseases, Treatment Outcome, Child, Preschool, HIV-1, Reverse Transcriptase Inhibitors, Female, Dried Blood Spot Testing, business, Viral load, HIV drug resistance
Abstract: Background In Africa a high percentage of HIV-infected children continue to experience HIV treatment failure despite enormous progress. In Benin (West Africa), there are currently no data on HIV drug resistance at failure in paediatric populations. Objectives To assess the frequency and patterns of HIV drug resistance among children with virological ART failures. Methods Dried blood spots from 62 HIV-infected children with virological failure were collected at the paediatric clinic of the National Hospital Center in Cotonou for genotyping and plasma drug concentration determination. Results Characteristics of the population show a median age of 10 years (IQR 6-13) and a median duration on ART of 5 years (IQR 3-7). Viruses from 53 children were successfully amplified. Of these, 76% of patients were on an NNRTI-based regimen and 24% on a boosted PI-based regimen. NRTI, NNRTI and dual-class resistance was present in 71%, 84% and 65% of cases, respectively. Only 4% of the children had major resistance mutations to PIs and none had major resistance mutations to integrase inhibitors. Among the participants, 25% had undetectable antiretroviral concentrations. Conclusions Our results showed that the development of drug resistance could be one of the main consequences of high and continuous viral replication in HIV-infected children in Benin. Thus, inadequate attention to monitoring lifelong ART in children may prevent achievement of the goal of the United Nations Program on HIV and AIDS (UNAIDS) of 90% viral suppression among patients receiving ART.
Published: 2018
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47. Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen

Author: Alexandre Storto, Diane Descamps, Anne Maillard, Audrey Mirand, Corinne Amiel, Charlotte Charpentier, Vincent Calvez, Thuy Van Nguyen, Laurence Bocket, Coralie Pallier, Audrey Rodallec, Elisabeth André-Garnier, Marie Leoz, Laurence Morand-Joubert, Isabelle Malet, Stéphanie Raymond, Véronique Schneider, Catherine Roussel, Camille Tumiotto, Constance Delaugerre, Anne-Geneviève Marcelin, Julia Dina, Jean-Christophe Plantier, Brigitte Montes, Anne Signori-Schmuck, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Tenon [APHP], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Microbiology (medical), Genotype, 030106 microbiology, Mutation, Missense, Integrase inhibitor, HIV Infections, HIV Integrase, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virus, 03 medical and health sciences, chemistry.chemical_compound, Gene Frequency, medicine, Prevalence, Humans, Pharmacology (medical), HIV Integrase Inhibitors, Pharmacology, biology, Elvitegravir, business.industry, Viral Load, Raltegravir, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Integrase, Regimen, Infectious Diseases, Treatment Outcome, chemistry, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, HIV-1, France, business, Viral load, medicine.drug
Abstract: International audience; ObjectivesTo assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.MethodsThis was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.ResultsPrevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL
Published: 2018
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48. Drug resistance and tropism as markers of the dynamics of HIV-1 DNA quasispecies in blood cells of heavily pretreated patients who achieved sustained virological suppression

Author: Caroline Lascoux-Combe, Jean-Paul Viard, Sidonie Lambert-Niclot, Catherine Fagard, Samira Fafi-Kremer, Pierre Gantner, Véronique Avettand-Fenoel, Jade Ghosn, Christine Rouzioux, Corinne Amiel, Dominique Salmon, Charlotte Sueur, Laurence Morand-Joubert, D. B. Fofana, and François Raffi
Subjects: 0301 basic medicine, Microbiology (medical), Genotype, Anti-HIV Agents, 030106 microbiology, HIV Infections, Viral quasispecies, Drug resistance, V3 loop, Biology, medicine.disease_cause, 03 medical and health sciences, HIV Protease, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), Longitudinal Studies, Tropism, Pharmacology, Mutation, Blood Cells, env Gene Products, Human Immunodeficiency Virus, High-Throughput Nucleotide Sequencing, Virology, HIV Reverse Transcriptase, Reverse transcriptase, Viral Tropism, Infectious Diseases, DNA, Viral, Immunology, HIV-1, Tissue tropism
Abstract: OBJECTIVES The objective of this study was to address the dynamics of archived resistant quasispecies in cell-associated HIV-1 DNA over time in heavily ART-experienced patients with currently suppressed plasma HIV-1 RNA. METHODS Longitudinal ultra-deep sequencing (UDS) analysis of reverse transcriptase, protease and V3 Env regions was performed on blood-cell-associated HIV-1 DNA samples. Drug-resistance-associated mutations (DRAMs) and tropism were interpreted using the ANRS and Geno2Pheno algorithms. We analysed frozen blood cells from patients enrolled in the INNOVE and ANRS 123 ETOILE studies who achieved sustained viral suppression after salvage optimized ART (SOT). RESULTS Samples were available at baseline and 6 and ≥12 months after SOT initiation in 10 patients. V3 loop sequences displayed wide intra-individual dynamics over time. Viral variants harbouring DRAMs exhibited three non-exclusive scenarios. First, when SOT exerted the same selective pressure as previous failing regimens, some viral quasispecies still harboured the same DRAMs at the same level as at the time of virological failure. Thus, as DRAMs were mostly associated with the same viral variant, variants with a complete resistance pattern remained archived. Second, some viral variants harbouring DRAMs were no longer detected over time when SOT consisted of new antiretroviral classes or had resistance profiles distinct from those of previous failing regimens. Third, variants with new DRAMs associated with SOT emerged in blood cells during follow-up despite sustained virological control. CONCLUSIONS Using longitudinal UDS analysis and focusing on DRAMs and tropism as markers, we demonstrated that, despite sustained virological control, archived HIV-1 DNA quasispecies continued to evolve.
Published: 2015
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49. Presence of Minority Resistant Variants After Failure of a Tenofovir, Emtricitabine, and Rilpivirine Regimen

Author: Jean-Luc Meynard, Anne-Geneviève Marcelin, Laure Surgers, Eve Todesco, Laurence Morand-Joubert, and Vincent Calvez
Subjects: 0301 basic medicine, Genotyping Techniques, Tenofovir, Anti-HIV Agents, 030106 microbiology, HIV Infections, Drug resistance, Emtricitabine, 03 medical and health sciences, chemistry.chemical_compound, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), business.industry, RNA-Directed DNA Polymerase, Rilpivirine, High-Throughput Nucleotide Sequencing, Viral Load, Virology, Regimen, 030104 developmental biology, Infectious Diseases, chemistry, HIV-1, business, Viral load, medicine.drug
Published: 2016
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50. Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant

Author: Samira Fafi-Kremer, Laurence Morand-Joubert, Audrey Mirand, Vincent Calvez, Cathia Soulié, Mary-Anne Trabaud, A G Marcelin, Jacqueline Cottalorda, Anne Signori-Schmuck, S. Berger, Julia Dina, Coralie Pallier, Véronique Avettand-Fenoel, Brigitte Montes, Pantxika Bellecave, Karen Zafilaza, Charlotte Charpentier, L. Le Guen, Sabine Yerly, Catherine Roussel, Corinne Amiel, Sophie Sayon, Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Virologie [Strasbourg], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), UR 0420 - Station de pathologie végétale, Laboratoire de pathologie forestière, Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain Recherche (SGR), SAINT-GOBAIN, CHU Pitié-Salpêtrière [APHP], Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbiologie Fondamentale et Pathogénicité (MFP), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Genotype, Genotyping Techniques, viruses, Concordance, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, ddc:616.07, HIV Envelope Protein gp120, Biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Virology, HIV tropism, medicine, Humans, False Positive Reactions, 030212 general & internal medicine, Tropism, ComputingMilieux_MISCELLANEOUS, virus diseases, Viral Load, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, CD4 Lymphocyte Count, 3. Good health, Viral Tropism, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Recombinant DNA, RNA, Viral, France, False positive rate, Viral load, Algorithm, Algorithms, Switzerland, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. Methods The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. Results Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. Conclusion Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.
Published: 2018

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