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1. Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study

Author: Stephanie Guillet, Etienne Crickx, Imane Azzaoui, pascal chappert, Emmanuelle Boutin, Jean-François Viallard, Etienne Riviere, Delphine Gobert, Lionel Galicier, Marion Malphettes, Stéphane Cheze, Francois Lefrere, Sylvain Audia, Bernard Bonnotte, Olivier Lambotte, Nicolas Noel, Olivier Fain, Guillaume Moulis, Mohamed Hamidou, Mathieu Gerfaud-Valentin, Jean-Pierre Marolleau, Louis Terriou, Nihal Martis, Anne-Sophie Morin, Antoinette Perlat, Thomas Le Gallou, Frédérique Roy-Peaud, Ailsa Robbins, Jean-Christophe Lega, Mathieu Puyade, Thibault Comont, Nicolas Limal, Laetitia Languille, Anissa Zarour, Marine Luka, Mickaël Mathieu Ménager, Thibaut Belmondo, Sophie Hue, Florence Canoui-Poitrine, Marc Michel, Bertrand Godeau, Matthieu Mahevas, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], 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 Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Necker - Enfants Malades [AP-HP], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974
Published: 2023

2. Immune interventions in COVID-19: a matter of time?

Author: Xavier Mariette, Q. Richier, Olivier Hermine, Nicolas Noel, Léo Plaçais, Karine Lacombe, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Bicêtre, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), and HAL-SU, Gestionnaire
Subjects: medicine.medical_specialty, Time Factors, Coronavirus disease 2019 (COVID-19), Immunology, Psychological intervention, Review Article, Antiviral Agents, Drug Administration Schedule, Immunomodulating Agents, Time frame, Immune system, Intervention (counseling), Pandemic, Animals, Humans, Immunology and Allergy, Medicine, Intensive care medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, COVID-19, medicine.disease, COVID-19 Drug Treatment, Clinical trial, Treatment Outcome, Host-Pathogen Interactions, Immunotherapy, business, Pneumonia (non-human), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Immunosuppressive Agents
Abstract: As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.
Published: 2022

3. Cerebrospinal fluid exposure to bictegravir/emtricitabine/tenofovir in HIV-1-infected patients with CNS impairment

Author: Jacques Gasnault, Pierre-Hadrien Becker, Lionelle Nkam, Antoine Cheret, Anne-Marie Taburet, Aurélie Barrail-Tran, Valérie Furlan, Pilartxo Catalan, Cécile Goujard, Thibaut Gelé, Hélène Gouget, Coralie Pallier, Alicia Castro Gordon, Service de pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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 Paris Cité (UPCité), Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Service de Virologie [Villejuif], Hôpital Paul Brousse, Service de Biochimie [AP-HP Hôpital Bicêtre], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Faculté de Médecine Paris-Saclay, and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay
Subjects: Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Pyridones, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Emtricitabine, Gastroenterology, Tenofovir alafenamide, Piperazines, Cerebrospinal fluid, Tandem Mass Spectrometry, Internal medicine, Oxazines, medicine, Humans, Pharmacology (medical), In patient, Tenofovir, Aged, Pharmacology, Alanine, Total plasma, Bictegravir, business.industry, Adenine, Middle Aged, Amides, Emtricitabine/Tenofovir, Infectious Diseases, HIV-1, Female, business, Heterocyclic Compounds, 3-Ring, Chromatography, Liquid, medicine.drug
Abstract: Objectives The penetration of antiretroviral drugs into deep compartments, such as the CNS, is a crucial component of strategies towards an HIV cure. This study aimed to determine CSF concentrations of bictegravir, emtricitabine and tenofovir in patients with HIV-related CNS impairment (HCI) enrolled in a real-life observational study. Methods Patients with HCI treated by optimized ART, including bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 1 month were enrolled. Plasma and CSF concentrations were measured by quality control-validated assays (LC-MS/MS). The inhibitory quotient (IQARV) was calculated as the ratio of unbound (bictegravir) or total (emtricitabine and tenofovir) concentration to half (or 90%) maximal inhibitory concentration for bictegravir (or emtricitabine and tenofovir). All numerical variables are expressed as median (range). Results Twenty-four patients (nine women) were enrolled. The age was 45 (26–68) years. Unbound bictegravir and total emtricitabine and tenofovir CSF concentrations were 4.4 (1.6–9.6), 84.4 (28.6–337.4) and 1.6 (0.7–4.3) ng/mL, respectively. The unbound bictegravir CSF fraction was 34% (15%–82%) versus 0.33% (0.11%–0.92%) in plasma. Three patients had an IQARV above unity for the three antiretrovirals. Factors positively associated with the CSF concentration (unbound for bictegravir) were age and total plasma concentration for the three antiretrovirals. Patients aged over 51 years had higher CSF concentrations (unbound for bictegravir). Conclusions We observed low CSF exposure to bictegravir, emtricitabine and tenofovir. These results suggest that BIC/FTC/TAF should be used with caution as first-line treatment for people living with HIV with HCI under 51 years of age.
Published: 2021

4. Risk Prediction Score for Screening Asymptomatic Sexually Transmitted Infections in HIV-positive French Men Who Have Sex with Men (ANRS 9520 DRIVER)

Author: Martin, Duracinsky, Svetlane, Dimi, Maria Patrizia, Carrieri, Issifou, Yaya, Virginie, Villes, Nadia, Valin, Eric, Farfour, Olivier, Chassany, David, Zucman, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris Cité (UPCité), Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Patient-Centered Outcomes Research [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, MESH: Sexual Behavior, Health (social science), MESH: Humans, MESH: Middle Aged, Social Psychology, Sexual Behavior, [SDV]Life Sciences [q-bio], Sexually Transmitted Diseases, Public Health, Environmental and Occupational Health, HIV Infections, MESH: HIV Infections, Middle Aged, MESH: Male, MESH: Homosexuality, Male, MESH: Sexual and Gender Minorities, Sexual and Gender Minorities, MESH: HIV Seropositivity, HIV Seropositivity, Humans, Homosexuality, Male, MESH: Sexually Transmitted Diseases
Abstract: International audience; Objectives: Asymptomatic sexually transmitted infections (STI) are frequent among men who have sex with men (MSM). Identifying asymptomatic STIs is a crucial issue, not only for secondary but also for primary prevention, as early treatment can reduce transmission risk. We aimed to develop a self-reported predictive score for early identification of asymptomatic STIs. Methods: Participants provided clinical data and completed a self-administered questionnaire including sociodemographic variables and behaviors during the 6 previous months. We used multivariable logistic regression to identify factors associated with asymptomatic STIs. We calculated the accuracy of the model by the non-parametric area (AUC) under the receiver-operating-characteristic (ROC) curve to find the optimal discriminant threshold for screening. Results:A total of 781 HIV-positive MSM were included with a mean age of 46.8 years. Asymptomatic STI prevalence was 13.2%. Detectable plasma HIV RNA (adjusted odds ratio (aOR [95% CI): 2.54 [1.23;5.25]), inconsistent condom use during anal sex (2.20 [1.36;3.56]), group sex (2.00 [1.15;3.45]), during or-genital practices (1.83 [1.12;3.01]), not being in stable relationship (1.70 [1.01;2.66] and an item from a sensation-seeking behavioral scale "I don't like watching porn videos" (1.61 [1.01;2.59] were associated with asymptomatic STI. AUC was 0.7 and with optimal threshold of 0.1082 for this model; sensitivity was 80.4%. Self-reported asymptomatic STI predictive score was built with this threshold according to the 6 factors in the final model. Conclusions: As this predictive score is not designed to be diagnostic, but to provide indications for diagnostic tests, its ease of administration and sensitivity remain the most important features. Its use in clinical practice for early detection of asymptomatic STIs potentially can reinforce STI primary and secondary prevention.
Published: 2022

5. Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study

Author: Stéphanie Guillet, Valentine Loustau, Emmanuelle Boutin, Anissa Zarour, Thibault Comont, Odile Souchaud-Debouverie, Nathalie Costedoat Chalumeau, Brigitte Pan-Petesch, Delphine Gobert, Stéphane Cheze, Jean Francois Viallard, Anne-Sophie Morin, Gaetan Sauvetre, Manuel Cliquennois, Bruno Royer, Agathe Masseau, Louis Terriou, Claire Fieschi, Olivier Lambotte, Stéphane Girault, Bertrand Lioger, Sylvain Audia, Karim Sacre, Jean Christophe Lega, Vincent Langlois, Alexandra Benachi, Corentin Orvain, Alain Devidas, Sebastien Humbert, Nicolas Gambier, Marc Ruivard, Virginie Zarrouk, Mikael Ebbo, Lise Willems, Lauriane Segaux, Matthieu Mahevas, Bassam Haddad, Marc Michel, Florence Canoui-Poitrine, Bertrand Godeau, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), 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 National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de référence maladie rare des cytopénies auto-immunes de l'adulte (GECAI - Hôpital Henri-Mondor - UPEC), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Service de Génomique Fonctionnelle, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hopital Saint-Louis [AP-HP] (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hématologie biologique [CHU Limoges], and CHU Limoges
Subjects: Purpura, Thrombocytopenic, Idiopathic, Immunology, Pregnancy Complications, Hematologic, Infant, Newborn, Cell Biology, Hematology, Biochemistry, Cohort Studies, Thrombocytopenia, Neonatal Alloimmune, Pregnancy, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Prospective Studies, Retrospective Studies
Abstract: The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (
Published: 2022

6. Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo

Author: Menegatti, Silvia, Guillemot, Vincent, Latis, Eleonora, Yahia-Cherbal, Hanane, Mittermüller, Daniela, Rouilly, Vincent, Mascia, Elena, Rosine, Nicolas, Koturan, Surya, Millot, Gaël, Leloup, Claire, Duffy, Darragh, Gleizes, Aude, Hacein-Bey-Abina, Salima, The Milieu Interieur, Consortium, Sellam, Jérémie, Berenbaum, Francis, Miceli-Richard, Corinne, Dougados, Maxime, Bianchi, Elisabetta, Rogge, Lars, Immunorégulation - Immunoregulation, Institut Pasteur [Paris], Université Sorbonne Paris Cité (USPC), Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Datactix, Immunologie Translationnelle - Translational Immunology lab, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [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), 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], Université Paris Descartes - Paris 5 (UPD5), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SM was a scholar of the Pasteur-Paris University (PPU) International PhD programme and supported by a grant from the Fondation pour la Recherche Médicale. EL was supported by a fellowship from the Université Paris Diderot. This study was Institut Pasteur, the French Government’s Investissement d’Avenir Programme, Laboratoire d’Excellence 'Milieu Intérieur' (ANR-10-LABX-69-01), FOREUM Foundation for Research in Rheumatology, the Fondation Arthritis, MSD Avenir (Project iCARE-SpA), a Bourse Passerelle from Pfizer., Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Trouvier, Marie-Noëlle Ungeheuer, Darragh Duffy, Matthew L. Albert, Lluis Quintana-Murci., ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris] (IP), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: rheumatoid arthritis, 0301 basic medicine, Chemokine, anti-TNF therapy, [SDV]Life Sciences [q-bio], tumor necrosis factor inhibitors, immune system diseases, Immunology, Inflammation, General Biochemistry, Genetics and Molecular Biology, TNF inhibitors, 03 medical and health sciences, 0302 clinical medicine, Immune system, Rheumatology, Immunity, Spondylarthritis, Spondyloarthritis, Humans, Immunology and Allergy, Medicine, Spondylitis, Ankylosing, 030203 arthritis & rheumatology, Innate immune system, biology, Tumor Necrosis Factor-alpha, business.industry, Interleukin, spondylitis, Chemotaxis, 3. Good health, chronic inflammatory diseases, ankylosing, 030104 developmental biology, biological therapy, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Tumor necrosis factor alpha, medicine.symptom, business
Abstract: ObjectivesAntitumour necrosis factor (TNF) therapy has revolutionised treatment of several chronic inflammatory diseases, including spondyloarthritis (SpA). However, TNF inhibitors (TNFi) are not effective in all patients and the biological basis for treatment failure remains unknown. We have analysed induced immune responses to define the mechanism of action of TNF blockers in SpA and to identify immunological correlates of responsiveness to TNFi.MethodsImmune responses to microbial and pathway-specific stimuli were analysed in peripheral blood samples from 80 patients with axial SpA before and after TNFi treatment, using highly standardised whole-blood stimulation assays. Cytokines and chemokines were measured in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, and gene expression was monitored using nCounter assays.ResultsAnti-TNF therapy induced profound changes in patients’ innate immune responses. TNFi action was selective, and had only minor effects on Th1/Th17 immunity. Modular transcriptional repertoire analysis identified prostaglandin E2 synthesis and signalling, leucocyte recirculation, macrophage polarisation, dectin and interleukin (IL)-1 signalling, as well as the nuclear factor kappa B (NF-kB) transcription factor family as key pathways targeted by TNF blockers in vivo. Analysis of induced immune responses before treatment initiation revealed that expression of molecules associated with leucocyte adhesion and invasion, chemotaxis and IL-1 signalling are correlated with therapeutic responses to anti-TNF.ConclusionsWe show that TNFi target multiple immune cell pathways that cooperate to resolve inflammation. We propose that immune response profiling provides new insight into the biology of TNF-blocker action in patients and can identify signalling pathways associated with therapeutic responses to biological therapies.
Published: 2020

7. Impact of the COVID-19 crisis on healthcare workers: The need to address quality of working life issues

Author: Fabienne Marcellin, Lorraine Cousin, Vincent Di Beo, Véronique Mahé, Olivia Rousset‐Torrente, Patrizia Carrieri, Olivier Chassany, Martin Duracinsky, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris Cité (UPCité), Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: Pulmonary and Respiratory Medicine, MESH: Humans, [SDV]Life Sciences [q-bio], MESH: COVID-19, MESH: Health Personnel, MESH: SARS-CoV-2
Abstract: International audience; See related Reply
Published: 2022

8. Use of psychoactive substances by night-shift hospital healthcare workers during the first wave of the COVID-19 pandemic: a cross-sectional study based in Parisian public hospitals (ALADDIN)

Author: Lorraine Cousin, Vincent Di Beo, Fabienne Marcellin, Sarah Coscas, Véronique Mahé, Isabelle Chavignaud, Olivia Rousset Torrente, Olivier Chassany, Martin Duracinsky, Maria Patrizia Carrieri, Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris Cité (UPCité), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Mission Fides - CME [Hôpital Paul-Brousse AP-HP] (MF), Hôpital Lariboisière-Fernand-Widal [APHP], Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: Male, MESH: Pandemics, Health Personnel, [SDV]Life Sciences [q-bio], occupational & industrial medicine, risk management, health & safety, MESH: Cross-Sectional Studies, MESH: Hospitals, Public, MESH: Alcoholism, Humans, MESH: COVID-19, MESH: SARS-CoV-2, Pandemics, MESH: Humans, Hospitals, Public, SARS-CoV-2, public health, COVID-19, MESH: Quality of Life, General Medicine, MESH: Male, Alcoholism, Cross-Sectional Studies, Quality of Life, MESH: Health Personnel, epidemiology
Abstract: ObjectivesThis study aimed to estimate the prevalence of psychoactive substance (PAS) use in night-shift healthcare workers (NSHW) during France’s first COVID-19 wave (March–May 2020).DesignObservational cross-sectional online survey.Setting39 public hospitals in the Assitance Publique des Hôpitaux de Paris (AP-HP) network in the Parisian area.ParticipantsA total of 1238 nurses, assistant nurses, X-ray technicians, managers, lab technicians, midwives and childcare assistants working at night or alternating between days and nights answered the questionnaire.InterventionOnline survey.Outcome measuresPAS use prevalence after weighting data for sex, age and profession using calibration on margins, in order to be representative of all AP-HP NSHW. We used the Fagerström scale and the Alcohol Use Disorders Identification Test Concise to assess PAS use.ResultsThe weighted estimated prevalences of daily smoking, alcohol drinking and tranquilliser use in participating NSHW were 21.4, 1.3 and 2.4%, respectively. Twelve per cent (11.7%) of our study sample used opioids. During the first COVID-19 wave, PAS use remained stable except for tobacco use, with 8.6% of participants reporting an increase. Previous 3-month prevalences of tranquilliser and opioid use were significantly higher than in the general population.ConclusionDaily smoking (especially in younger men) and tranquilliser and opioid use were highly prevalent in NSHW in the AP-HP network during France’s first COVID-19 wave. Specific interventions for quitting smoking and addressing determinants of tranquilliser and opioid use in NSHW need to be developed and evaluated to improve quality of life in these essential, underdiagnosed and undertreated health personnel.
Published: 2022

9. Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma

Author: Patrick Schmid, Enos Bernasconi, Ioannis Theodorou, Sophia S. Wang, Pejman Mohammadi, Paul J. McLaren, Huldrych F. Günthard, Matthias Cavassini, Charles S. Rabkin, Matthias Hoffmann, Christian Hammer, Shehnaz K. Hussain, Jacques Fellay, Andri Rauch, Cécile Goujard, Laurence Meyer, Jonathan Niay, Caroline Besson, Nava Ehsan, Tiphaine Oudot-Mellakh, Dominique Costagliola, Manuel Battegay, Christian W. Thorball, Federico Santoni, Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), University of California-University of California, Genentech, Inc. [San Francisco], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), 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 recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Beckman Research Institute of the City of Hope, Cedars-Sinai Medical Center, Lausanne University Hospital, Bern University Hospital [Berne] (Inselspital), University of Bern, University Hospital Basel [Basel], Cantonal Hospital of Olten, Cantonal Hospital St Gallen (KSSG), Lugano Regional Hospital [Lugano], University hospital of Zurich [Zurich], National Microbiology Laboratory [Winnipeg, Canada], Public Health Agency of Canada, University of Manitoba [Winnipeg], Centre Hospitalier de Versailles André Mignot (CHV), University of Zurich, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 10028 Institute of Medical Virology, Follicular lymphoma, HIV Infections, Genome-wide association study, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin, hemic and lymphatic diseases, BATF, Immunodeficiency, Lymphoma, AIDS-Related, variants, 0303 health sciences, education.field_of_study, common, Anti-Retroviral Agents/therapeutic use, Case-Control Studies, Chemokine CXCL12, Genome-Wide Association Study, HIV Infections/complications, HIV Infections/drug therapy, HIV Infections/genetics, Humans, Lymphoma, AIDS-Related/drug therapy, Lymphoma, Non-Hodgkin/drug therapy, Lymphoma, Non-Hodgkin/genetics, Polymorphism, Genetic, Lymphoma, Non-Hodgkin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: HIV Infections, Hematology, MESH: Case-Control Studies, 3. Good health, Anti-Retroviral Agents, 030220 oncology & carcinogenesis, loci, MESH: Chemokine CXCL12, Population, 610 Medicine & health, Biology, MESH: Anti-Retroviral Agents, Article, infected individuals, 03 medical and health sciences, follicular lymphoma, expression, MESH: Polymorphism, Genetic, Genetic variation, cancer-risk, medicine, education, MESH: Lymphoma, AIDS-Related, 030304 developmental biology, Genetic association, MESH: Humans, chemokine, medicine.disease, Lymphoma, MESH: Genome-Wide Association Study, Immunology, genome-wide association, immunodeficiency
Abstract: International audience; Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.
Published: 2020

10. Social and professional recognition are key determinants of quality of life at work among night-shift healthcare workers in Paris public hospitals (AP-HP ALADDIN COVID-19 survey)

Author: Duracinsky, Martin, Marcellin, Fabienne, Cousin, Lorraine, Di Beo, Vincent, Mahé, Véronique, Rousset-Torrente, Olivia, Carrieri, Patrizia, Chassany, Olivier, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris Cité (UPCité), Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), and Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal
Subjects: MESH: Pandemics, MESH: Humans, Hospitals, Public, [SDV]Life Sciences [q-bio], Health Personnel, MESH: Delivery of Health Care, MESH: Quality of Life, COVID-19, MESH: Cross-Sectional Studies, MESH: Hospitals, Public, Cross-Sectional Studies, Quality of Life, MESH: COVID-19, MESH: Health Personnel, Humans, Delivery of Health Care, Pandemics
Abstract: Objective: Documenting the perceptions and experiences of frontline healthcare workers during a sanitary crisis is key to reinforce healthcare systems. We identify the determinants of quality of working life (QWL) among night-shift healthcare workers (NSHW) in Paris public hospitals shortly after the first-wave of the COVID-19 pandemic.Methods: The ALADDIN cross-sectional online survey (15 June to 15 September 2020) collected QWL, socio-economic, behavioral, and work-related information among 1,387 NSHW in the 39 hospitals of the Assistance Publique-Hôpitaux de Paris (AP-HP). Data were weighted (margin calibration) to be representative of the entire population of 12,000 AP-HP hospitals' NSHW regarding sex, age, and professional category. Linear regression was used to identify correlates of QWL (WRQoL scale).Results: New night position during the COVID pandemic, difficulties in getting screened for COVID, and considering protective measures inadequate were associated with poorer QWL, after adjustment for socio-economic characteristics, professional category, perceived health, physical activity, and history of harassment at work. Under-estimation of night-shift work by day-shift colleagues, reporting night work as a source of tension with friends, or feeling more irritable since working at night also impaired QWL. By contrast, satisfaction regarding COVID information received from the employer, and feeling valued by the general population during the pandemic improved QWL.Conclusions: Insufficient access to screening, information, and protective measures impaired QWL of NSHW after the first wave of COVID-19 in Paris public hospitals. Social and professional recognition of night-shift work were the key determinants of QWL in this population.
Published: 2021

11. Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

Author: Bourgeois, Christine, Gorwood, Jennifer, Olivo, Anaelle, Le Pelletier, Laura, Capeau, Jacqueline, Lambotte, Olivier, Béréziat, Véronique, Lagathu, Claire, Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Inflammation, antiretroviral treatment, chronic inflammation, chronic immune activation, Anti-HIV Agents, Adipose Tissue, White, [SDV]Life Sciences [q-bio], Immunology, HIV Infections, Review, HIV infection, adipose tissue, fat, Animals, Humans, Obesity
Abstract: International audience; White adipose tissue (AT) contributes significantly to inflammation - especially in the context of obesity. Several of AT's intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Besides, reducing ART toxicities remains a crucial therapeutic goal.
Published: 2021

12. Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

Author: Philippe Horellou, Aliénor de Chalus, Laetitia Giorgi, Carole Leroy, Pascale Chrétien, Salima Hacein-Bey-Abina, Christine Bourgeois, Xavier Mariette, Ché Serguera, Roger Le Grand, Kumaran Deiva, Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], 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 Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut du Cerveau = Paris Brain Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, myelin oligodendrocyte glycoprotein, Lymphocyte Activation, multiple sclerosis, Autoantigens, T-Lymphocytes, Regulatory, neuroinflammation, 0302 clinical medicine, Recurrence, T-Lymphocyte Subsets, immune system diseases, Immunology and Allergy, auto-immune diseases, Age of Onset, Child, Original Research, biology, Age Factors, FOXP3, hemic and immune systems, regulatory T lymphocytes, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Disease Susceptibility, Antibody, Adolescent, Immunology, chemical and pharmacologic phenomena, Peripheral blood mononuclear cell, Myelin oligodendrocyte glycoprotein, Autoimmune Diseases, Immunophenotyping, 03 medical and health sciences, acquired demyelinating syndromes (ADS), Antigen, medicine, Humans, Neuroinflammation, Autoantibodies, Autoimmune disease, business.industry, Multiple sclerosis, RC581-607, medicine.disease, 030104 developmental biology, Case-Control Studies, biology.protein, Myelin-Oligodendrocyte Glycoprotein, Immunologic diseases. Allergy, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: BackgroundMyelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative.AimsTo identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing versus non-relapsing subgroups of MOGAD.MethodsThree groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4+ T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (Tregs, Foxp3+), CD45RA-Foxp3+ Tregs and subpopulation naive Tregs (CD45RA+Foxp3int), effector Tregs (CD45RA-Foxp3high) and non-suppressive Tregs (CD45RA-Foxp3int) proportions were determined.ResultsThe mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4+ Tregs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA-Foxp3+ Tregs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector Tregs/non suppressive-Tregs, which was significantly higher than in MOGNR.ConclusionsOur findings suggest that CD4+ Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of Tregs to rh-MOG in MOGNR, where CD4+ Tregs increased, and in MOGR, where CD45RA-Foxp3+ Tregs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease.
Published: 2021

13. Anti-gp41 antibody levels reflect HIV viral suppression and cellular reservoir in long-term antiretroviral-treated trial participants

Author: Corinne Jadand, Maxime Grude, Mathilde Ghislain, Marie-Laure Nere, Vincent Calvez, Laurence Meyer, Francis Barin, Philippe Flandre, Heloise Delagreverie, Cécile Goujard, Sidonie Lambert-Niclot, François Raffi, Catherine Leport, Christine Katlama, Constance Delaugerre, Gestionnaire, Hal Sorbonne Université, 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), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), 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), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), Time Factors, Sustained Virologic Response, Anti-HIV Agents, [SDV]Life Sciences [q-bio], 030106 microbiology, HIV Infections, Antibodies, Viral, Virus, 03 medical and health sciences, 0302 clinical medicine, Antigen, Antiretroviral Therapy, Highly Active, HIV Seropositivity, Humans, Medicine, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pharmacology, biology, medicine.diagnostic_test, business.industry, Antibody titer, virus diseases, Middle Aged, HIV Envelope Protein gp41, [SDV] Life Sciences [q-bio], Titer, Cross-Sectional Studies, Infectious Diseases, Immunoassay, Immunology, HIV-1, biology.protein, RNA, Viral, Biomarker (medicine), Female, France, Antibody, business
Abstract: Background A major challenge to HIV cure strategies is the quantification of persistent reactivation-prone virus in people living with HIV. Objectives To determine whether anti-gp41 antibody levels correlate with viral suppression and HIV-1 DNA levels in patients on ART. Methods Participants with plasma HIV-1 RNA below 50 copies/mL for >12 months were included from three ANRS cohorts (COPANA, MONOI and APROCO). Antibody levels to gp41 were measured by a low-sensitivity enzyme-linked immunoassay. Correlations with patient and virus characteristics, plasma HIV-1 RNA load (standard and ultrasensitive tests) and cell-associated HIV-1 DNA were assessed. Results Median age was 41 years and 77.5% of the 683 participants were men. Median CD4+ T cell count was 582 cells/mm3 and median viral suppression duration was 6.6 years (IQR 2.0-9.5). The overall median anti-gp41 antibody titre was 1.3 (IQR 0.6-1.9); median HIV-1 DNA level was 2.6 (IQR 2.1-3.0) log10 copies/106 leucocytes; and HIV-1 RNA was undetectable in 56% of samples. A lower titre of anti-gp41 antibodies correlated with male gender, longer viral suppression and lower HIV-1 DNA burden. Sustained undetectable HIV-1 RNA was associated with lower anti-gp41 levels [median 1.1 (IQR 0.5-1.6) versus 1.4 (IQR 0.7-1.9), P = 0.009]. Conclusions Anti-gp41 levels decreased with the duration of antiviral suppression on ART. Lower titres were associated with lower HIV-1 DNA levels and longer duration of viral suppression, reflecting minimal antigen stimulation. Anti-gp41 antibody titration may be a useful biomarker reflecting long-term HIV-1 suppression on ART.
Published: 2019

14. CXCR3 and CXCR5 are highly expressed in HIV‐1‐specific CD8 central memory T cells from infected patients

Author: Benoit Favier, Laurence Meyer, Anaelle Olivo, Géraldine Schlecht-Louf, Marie Bitu, Camille Lécuroux, Véronique Avettand-Fenoel, Faroudy Boufassa, Christine Bourgeois, Cécile Goujard, Bruno Vaslin, Asma Essat, Nicolas Noel, Olivier Lambotte, Jean-Marc Doisne, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Paris Cité (UPCité), Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Agence Nationale de Recherches sur le Sida et les Hépatites Virales. Grant Number: ECTZ117636, Doisne, Jean-Marc, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Receptors, CXCR5, 0301 basic medicine, Senescence, Receptors, CXCR3, Chemokine receptor, [SDV]Life Sciences [q-bio], Immunology, HIV Infections, Migratory profile, CD8-Positive T-Lymphocytes, Biology, CXCR3, CXCR5, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, CX3CR1, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, HIV controller, Middle Aged, HIV infection, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, HIV-1, Female, Immunologic Memory, Memory T cell, CD8, 030215 immunology, CD8 T cell
Abstract: International audience; New ways of characterizing CD8+ memory T cell responses in chronic infections are based on the measurement of chemokine receptor expression (CXCR3, CXCR5, and CX3CR1). We applied these novel phenotyping strategies to chronic HIV infection by comparing healthy donors (HDs), HIV-infected patients receiving antiretroviral therapy (ART), and spontaneous HIV controllers (HICs). In all groups, the memory cells exhibited high proportion of CXCR3+ cells. Proportions of CXCR5+ and CX3CR1+ cells were preferentially observed among central memory cells (Tcm) and effector memory cells (Tem) respectively. Chronic controlled HIV infection impacted the chemokine receptor profile of both HIV-specific and nonspecific CD8+ T cells. In total CD8+ T cells, the proportions of CXCR3- CXCR5- CX3CR1- Tcm and Tem were lower in HIV-infected patients than in HDs with subtle differences between ART and HICs. Such phenotyping strategy also revealed differences in exhaustion and senescence phenotypes, the CXCR3+ CXCR5+ CX3CR1- being more exhausted and senescent than the CXCR3+ CXCR5- CX3CR1- Tcm fraction. Among HIV-specific CD8+ T cells, the vast majority of Tcm cells were CXCR3+ and CXCR5+ cells in contrast with their nonspecific counterparts. In conclusion, the addition of migration markers contributes to better characterize Tcm/Tem compartment.
Published: 2021

15. Prospective evaluation of blood Epstein-Barr virus DNA load and antibody profile in HIV-related non-Hodgkin lymphomas

Author: Sophie Prevot, Raphaele Germi, Nicolas Mounier, Yassine Taoufik, Michele Algarte-Genin, Dominique Costagliola, Patrice Morand, Rémi Lancar, Anastasiia Filippova, Houria Hendel-Chavez, Bruno Marchou, Julien Lupo, Caroline Besson, Marie-Caroline Meyohas, Marialuisa Partisani, Fabrice Bonnet, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Hôpital l'Archet, Les Hôpitaux Universitaires de Strasbourg (HUS), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Admin, Oskar, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, medicine.medical_specialty, Immunology, medicine.disease_cause, Gastroenterology, Virus, Serology, Epstein–Barr virus, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Immunology and Allergy, 030212 general & internal medicine, Epstein–Barr virus antibodies, Whole blood, biology, business.industry, HIV, Non-Hodgkin's lymphoma, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Epstein–Barr virus DNA load, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, business, Viral load
Abstract: International audience; Objectives: The value of Epstein–Barr virus (EBV) biomarkers on the prognosis of HIV-related non-Hodgkin's lymphoma (NHL) has been poorly explored in the combined antiretroviral therapy (cART) era. Design: We evaluated EBV DNA load and EBV antibodies in HIV-NHL patients enrolled in the French ANRS-CO16 Lymphovir Cohort between 2008 and 2015. Methods: Whole blood and plasma EBV DNA load and serological profiles were analyzed in 76 HIV-infected patients at diagnosis of NHL and 6 months after the initiation of chemotherapy. Results: Prechemotherapy whole blood (WB) and plasma EBV DNA loads were positive for 80 and 45% of HIV-NHL patients, respectively. Pretreatment WB EBV DNA positivity was associated with a positive plasma HIV-1 RNA load (relative risk (RR), 4.42 [1.33; 14.72]) and plasma EBV DNA positivity with EBV in situ detection (RR 10.62 [2.38; 47.49]). Following chemotherapy, the proportions of patients with positive WB or plasma EBV DNA declined from 81 to 23% (P < 0.0001) and from 43 to 8% (P < 0.0001), respectively. Estimated 2-year progression-free survival did not differ according to prechemotherapy WB positivity (82% versus 67%, P = 0.15) or plasma EBV DNA positivity (76% versus 81%, P = 0.52). Conclusions: The plasma EBV DNA load correlates with in situ EBV detection. The WB EBV DNA load correlates with HIV load. WB and plasma EBV DNA loads at NHL diagnosis do not constitute prognostic markers for HIV-NHL patients in the modern cART era.
Published: 2021

16. Pain and dyspnea control during awake fiberoptic bronchoscopy in critically ill patients: safety and efficacy of remifentanil target-controlled infusion

Author: Matthieu Turpin, Thomas Baury, Sophie Dupeyrat, Antoine Parrot, Jean-Pierre Fulgencio, Margot Caron, Muriel Fartoukh, Alexandre Elabbadi, Daisy Daigné, Marie-Cécile Allain, Clarisse Blayau, Pierre-Yves Blanchard, Tài Pham, Sacha Rozencwajg, Aude Gibelin, Séverine Rodriguez, Service d'Anesthésie réanimation [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 de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: medicine.medical_specialty, medicine.drug_class, Sedation, Remifentanil, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Anesthesiology, medicine, Intensive care unit, Flexible fiberoptic bronchoscopy, Critically ill, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Comfort, 3. Good health, 030228 respiratory system, Sedative, Anesthesia, Anxiety, Observational study, Remifentanil target-controlled infusion, medicine.symptom, business, Tolerance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Purpose Flexible fiberoptic bronchoscopy is frequently used in intensive care unit, but is a source of discomfort, dyspnea and anxiety for patients. Our objective was to assess the feasibility and tolerance of a sedation using remifentanil target-controlled infusion, to perform fiberoptic bronchoscopy in awake ICU patients. Materials, patients and methods This monocentric, prospective observational study was conducted in awake patients requiring fiberoptic bronchoscopy. In accordance with usual practices in our center, remifentanil target-controlled infusion was used under close monitoring and adapted to the patient’s reactions. The primary objective was the rate of successful procedures without additional analgesia or anesthesia. The secondary objectives were clinical tolerance and the comfort of patients (graded from “very uncomfortable” to “very comfortable”) and operators (numeric scale from 0 to 10) during the procedure. Results From May 2014 to December 2015, 72 patients were included. Most of them (69%) were hypoxemic and admitted for acute respiratory failure. No additional medication was needed in 96% of the patients. No severe side-effects occurred. Seventy-eight percent of patients described the procedure as “comfortable or very comfortable”. Physicians rated their comfort with a median [IQR] score of 9 [8–10]. Conclusion Remifentanil target-controlled infusion administered to perform awake fiberoptic bronchoscopy in critically ill patients is feasible without requirement of additional analgesics or sedative drugs. Clinical tolerance as well as patients’ and operators’ comfort were good to excellent. This technique could benefit patients’ experience.
Published: 2021

17. Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

Author: N. Noel, Amélie Deleporte, Anne-Laure Voisin, Jean-Marie Michot, Stéphane Champiat, Léo Plaçais, Capucine Baldini, Aurélien Marabelle, Céline Labeyrie, Stéphanie Dehette, Patricia Romano-Martin, Adeline Not, Olivier Lambotte, Maria Silva Joao, Andoni Echaniz-Laguna, Alexandre Thibault Jacques Maria, David H. Adams, Guillemette Beaudonnet, Agathe Masseau, Cécile Cauquil, A. Laparra, Christian Denier, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Compiègne-Noyon (CHCN), Centre Hospitalier Compiègne-Noyon, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Salvy-Córdoba, Nathalie
Subjects: medicine.medical_specialty, Immune checkpoint inhibitors, medicine.medical_treatment, rechallenge, Corticosteroid treatment, paraneoplastic syndrome, immune checkpoint inhibitors, Internal medicine, medicine, neurological toxicity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, Adult patients, business.industry, AcademicSubjects/SCI01870, Mortality rate, General Engineering, Common Terminology Criteria for Adverse Events, Immunotherapy, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cohort, immune-related adverse events, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Original Article, AcademicSubjects/MED00310, business
Abstract: Neurological immune-related adverse events are complications of programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies that can be life threatening and often lead to anticancer immunotherapy withdrawal. Scant clinical data are available that integrate the clinical presentation, therapeutic management and long-term outcome. All consecutive adult patients treated by programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies, given alone or in combination with other treatment, who experienced a neurological immune-related adverse event with a severity grade ≥2 in Paris Saclay-University hospitals were investigated from June 2014 to February 2019. The frequency of neurological immune-related adverse events was calculated from the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Forty patients presenting with 51 distinct neurological immune-related adverse events were included. The prevalence of grade ≥2 neurological immune-related adverse events was estimated to be 1.22% in the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Among 40 patients with neurological immune-related adverse events, 65% received programmed-cell death 1 or programmed-cell death 1 ligand monotherapy and 35% received a combination of programmed-cell death 1 plus anti-CTLA4 (Common Terminology Criteria for Adverse Events). Clinical neurological presentations were peripheral (48%), central (35%), or mixed (18%). The severity of neurological immune-related adverse events was grade 2 for 14 (35%) and ≥grade 3 for 26 patients (65%). The mortality rate related to neurological immune-related adverse events was 8%. Corticosteroid treatment led to neurological recovery in 74%. Long-term follow-up highlighted that 53% of patients experienced long-term neurological sequelae. Five patients were rechallenged by programmed-cell death 1 monotherapy without recurrence of their neurological immune-related adverse event(s). Neurological immune-related adverse events induced by programmed-cell death 1 or programmed-cell death 1 ligand are rare but are severe with a mortality rate of 8% and long-term sequelae for 53% of patients. Corticosteroids should be started when neurological immunological complications are identified to avoid long-term sequelae., Plaçais et al. report a large case-series of 40 patients presenting with 51 neurological adverse events of immune checkpoint inhibitors, wherein corticosteroid therapy was associated with a 74% rate of neurological recovery. Neurological adverse events were severe, as 7.5% of the included patients died and 53% kept long-term neurological sequelae., Graphical Abstract Graphical Abstract
Published: 2021

18. Tocilizumab in Coronavirus Disease 2019: Give It Time!

Author: Léo Plaçais, Q. Richier, Karine Lacombe, Olivier Hermine, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), and HAL-SU, Gestionnaire
Subjects: Microbiology (medical), 2019-20 coronavirus outbreak, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Antibodies, Monoclonal, Humanized, Virology, COVID-19 Drug Treatment, chemistry.chemical_compound, AcademicSubjects/MED00290, Tocilizumab, Infectious Diseases, chemistry, Correspondence, Humans, Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Published: 2021

19. Optimal maturation of the SIV-specific CD8 + T-cell response after primary infection is associated with natural control of SIV. ANRS SIC study

Author: Roger Le Grand, Jeremie Guedj, Nathalie Bosquet, Antoine Blancher, David Price, Annie David, Bruno Vaslin, Gianfranco Pancino, Emma Gostick, Naya Sylla, Olivier Lambotte, Caroline Passaes, Pierre Versmisse, Véronique Avettand-Fenoel, Vincent Madelain, Valérie Monceaux, Asier Sáez-Cirión, Christine Rouzioux, Antoine Millet, Michaela Müller-Trutwin, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), 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), Cardiff University, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Service de Microbiologie Clinique [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), 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), Passaes, Caroline, HIV, Inflammation et persistance, Institut Pasteur [Paris], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), and CHU Toulouse [Toulouse]
Subjects: 0303 health sciences, [SDV.IMM] Life Sciences [q-bio]/Immunology, Period (gene), animal diseases, Memory pool, virus diseases, Viremia, Biology, medicine.disease, Phenotype, Macaque, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, biology.animal, Immunology, medicine, Potency, Cytotoxic T cell, [SDV.IMM]Life Sciences [q-bio]/Immunology, CD8, 030304 developmental biology, 030215 immunology
Abstract: Highly efficient virus-specific CD8+ T-cells are associated with immune control of HIV infection, but it remains unclear how these cells are generated and maintained over time. We used a macaque model of spontaneous control of SIVmac251 infection to monitor the development and evolution of potent antiviral CD8+ T-cell responses. SIV-specific CD8+ T-cells emerged during primary infection in all animals. However, the ability of CD8+ T cells to suppress SIV replication was low in early stages but increased after a period of maturation, temporally linked with the establishment of sustained low-level viremia in controller macaques. SIV-specific CD8+ T-cells with a central memory phenotype expressed higher levels of survival markers in controllers versus non-controllers. In contrast, a persistently skewed differentiation phenotype was observed among central memory SIV-specific CD8+ T-cells in non-controllers since primary infection, typified by relatively high expression levels of T-bet.Collectively, these data show that the phenotype of SIV-specific CD8+ T-cells defined early after SIV infection favor the gain of antiviral potency as a function of time in controllers, whereas SIV-specific CD8+ T-cell responses in non-controllers fail to gain antiviral potency due to early defects imprinted in the central memory pool.
Published: 2020

20. Characterization of Physicians That Might Be Reluctant to Propose HIV Cure-Related Clinical Trials with Treatment Interruption to Their Patients? The ANRS-APSEC Study

Author: Marie Suzan-Monti, Laurence Meyer, Lisa Fressard, Christel Protière, Marion Mora, Bruno Spire, Marie Préau, Jean-Daniel Lelièvre, Olivier Lambotte, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), 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), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), The Apsec Study Group, and Dupuis, Christine
Subjects: 0301 basic medicine, medicine.medical_specialty, physicians, principal component analysis, [SDV]Life Sciences [q-bio], Immunology, Human immunodeficiency virus (HIV), HIV cure-related clinical trials, lcsh:Medicine, Scientific literature, medicine.disease_cause, Article, analytical treatment interruption studies, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, medicine, Antiretroviral treatment, Pharmacology (medical), 030212 general & internal medicine, Hiv transmission, Pharmacology, business.industry, lcsh:R, Viewpoints, Continuous training, 3. Good health, HIV cure research, [SDV] Life Sciences [q-bio], Clinical trial, 030104 developmental biology, Infectious Diseases, Treatment interruption, Family medicine, multivariable linear regression, business, viewpoints
Abstract: International audience; HIV cure-related clinical trials (HCRCT) with analytical antiretroviral treatment interruptions (ATIs) have become unavoidable. However, the limited benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians' motivations to propose HCRCT to patients. Between October 2016 and March 2017, 164 French HIV physicians were asked about their level of agreement with four viewpoints regarding HCRCT. A reluctance score was derived from their answers and factors associated with reluctance identified. Results showed the highest reluctance to propose HCRCT was among physicians with a less research-orientated professional activity, those not informing themselves about cure trials through scientific literature, and those who participated in trials because their department head asked them. Physicians' perceptions of the impact of HIV on their patients' lives were also associated with their motivation to propose HCRCT: those who considered that living with HIV means living with a secret were more motivated, while those worrying about the negative impact on person living with HIV's professional lives were more reluctant. Our study highlighted the need to design a HCRCT that minimizes constraints for participants and for continuous training programs to help physicians keep up-to-date with recent advances in HIV cure research.
Published: 2020

21. A Machine Learning Approach for High-Dimensional Time-to-Event Prediction With Application to Immunogenicity of Biotherapies in the ABIRISK Cohort

Author: Julianne Duhazé, Signe Hässler, Delphine Bachelet, Aude Gleizes, Salima Hacein-Bey-Abina, Matthieu Allez, Florian Deisenhammer, Anna Fogdell-Hahn, Xavier Mariette, Marc Pallardy, Philippe Broët, CHU Sainte Justine [Montréal], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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 National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'épidémiologie, biostatistique et recherche clinique, 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), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Innsbruck Medical University [Austria] (IMU), Karolinska Institutet [Stockholm], Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Inflammation, microbiome, immunosurveillance (MI2), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Subjects: Adult, Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Adolescent, Computer science, Immunology, Population, High dimensional, immunogenicity, Machine learning, computer.software_genre, Autoimmune Diseases, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Humans, Immunology and Allergy, education, Aged, Original Research, Event (probability theory), Aged, 80 and over, education.field_of_study, business.industry, Immunogenicity, prediction, Middle Aged, survival random forest, 3. Good health, Random forest, Biological Therapy, 030104 developmental biology, machine learning, Antibody Formation, Cohort, biotherapy, Predictive power, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Artificial intelligence, Predictive variables, business, lcsh:RC581-607, computer, 030215 immunology
Abstract: International audience; Predicting immunogenicity for biotherapies using patient and drug-related factors represents nowadays a challenging issue. With the growing ability to collect massive amount of data, machine learning algorithms can provide efficient predictive tools. From the bio-clinical data collected in the multi-cohort of autoimmune diseases treated with biotherapies from the ABIRISK consortium, we evaluated the predictive power of a custom-built random survival forest for predicting the occurrence of anti-drug antibodies. This procedure takes into account the existence of a population composed of immune-reactive and immune-tolerant subjects as well as the existence of a tiny expected proportion of relevant predictive variables. The practical application to the ABIRISK cohort shows that this approach provides a good predictive accuracy that outperforms the classical survival random forest procedure. Moreover, the individual predicted probabilities allow to separate high and low risk group of patients. To our best knowledge, this is the first study to evaluate the use of machine learning procedures to predict biotherapy immunogenicity based on bioclinical information. It seems that such approach may have potential to provide useful information for the clinical practice of stratifying patients before receiving a biotherapy.
Published: 2020

22. Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

Author: Laurent Blum, Cécile Goujard, Laurence Meyer, Asma Essat, Véronique Avettand-Fenoel, Camille Lécuroux, Jean-Michel Molina, Christine Bourgeois, Sophie Novelli, Jacques Reynes, Agnès Villemant, Odile Launay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier René Dubos [Pontoise], 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 Paris Cité (UPCité), 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-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7), MSD France Agence Nationale de Recherches sur le Sida et les Hépatites Virales, ANRS, Dr. Avettand-Fenoël reports grants from ANRS, during the conduct of the study, grants and personal fees from ViiV, grants from Janssen, outside the submitted work. Dr. Reynes reports personal fees and non-financial support from Gilead Science, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from MSD France, personal fees and non-financial support from Janssen, personal fees and non-financial support from Pfizer, outside the submitted work. Dr. Molina reports personal fees from Gilead Sciences, personal fees from Merck, personal fees from ViiV Healthcare, outside the submitted work. Dr. Launay reports grants from Assistance Publique - Hopitaux de Paris (AP-HP), during the conduct of the study. Dr. Novelli, Dr. Lécuroux, Dr. Villemant, Dr. Essat, Dr. Blum , Dr. Bourgeois, Dr. Goujard and Dr. Meyer have nothing to disclose., This work was supported by the French Agency for Research on AIDS and Viral Hepatitis ( ANRS ) and a doctoral grant from Paris-Saclay University to Sophie Novelli., HAL UVSQ, Équipe, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, Overweight, medicine.disease_cause, Monocytes, Persistence (computer science), 0302 clinical medicine, Risk Factors, Antiretroviral Therapy, Highly Active, Immunodeficiency, lcsh:R5-920, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, Host-Pathogen Interactions, Cohort, Cytokines, Female, Inflammation Mediators, medicine.symptom, lcsh:Medicine (General), Research Paper, Adult, medicine.medical_specialty, Inflammation, General Biochemistry, Genetics and Molecular Biology, Long-term ART, 03 medical and health sciences, Internal medicine, medicine, Humans, Immune activation, business.industry, Monocyte, lcsh:R, medicine.disease, HIV infection, 030104 developmental biology, HIV-1, business, Body mass index, Biomarkers
Abstract: International audience; Background: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours. Methods: We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers. Findings: After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis. Interpretation: Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI. Funding: ANRS and Paris-Saclay University.
Published: 2020

23. Anti‐ HIV ‐1 antibodies trigger non‐lytic complement deposition on infected cells

Author: Ludivine Grzelak, Valérie Lorin, Julian Buchrieser, Guillaume Mestrallet, Katia Bourdic, Jérémy Dufloo, Timothée Bruel, Emilie Dupouy, Olivier Schwartz, Olivier Lambotte, Florence Guivel-Benhassine, Hugo Mouquet, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Work in OS laboratory is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), the Labex IBEID (ANR-10-IHUB-0002), the 'TIMTAMDEN' ANR-14-CE14-0029, the 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, L'Oréal Sponsorship, and the Gilead HIV cure program. HM is supported by the European Research Council (ERC)—Seventh Framework Program (ERC-2013-StG 337146), the G5 Institut Pasteur Program, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, and the ANRS. JD is supported by a grant from the French Ministry of Higher Education, Research and Innovation., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Virus et Immunité, 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), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Work in OS laboratory is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR‐10‐LABX‐77), the Labex IBEID (ANR‐10‐IHUB‐0002), the 'TIMTAMDEN' ANR‐14‐CE14‐0029, the 'CHIKV‐Viro‐Immuno' ANR‐14‐CE14‐0015‐01, L'Oréal Sponsorship, and the Gilead HIV cure program. HM is supported by the European Research Council (ERC)—Seventh Framework Program (ERC‐2013‐StG 337146), the G5 Institut Pasteur Program, the Milieu Intérieur Program (ANR‐10‐LABX‐69‐01), the INSERM, and the ANRS. JD is supported by a grant from the French Ministry of Higher Education, Research and Innovation., We thank members of the Virus and Immunity Unit for discussion and help. We thank patients who participated in the study and Cécile Goujard for supervision of the patients’ enrollment. We thank the NIH AIDS Reagent Program for providing reagents. We thank Michel C. Nussenzweig (The Rockefeller University) for providing the pMX‐YU2 ENVΔCT‐GFP‐PuroR expression vector. We thank Frank Kirchhoff and Daniel Sauter (Ulm University) for providing CH058, CH058∆Nef, CH058∆Vpu, and CH058∆Nef∆Vpu plasmids., and ANR-10-LABX-0077/10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010)
Subjects: [SDV]Life Sciences [q-bio], MESH: Complement System Proteins, HIV Infections, CD59, V3 loop, HIV Antibodies, Biochemistry, MESH: HIV-1, 03 medical and health sciences, 0302 clinical medicine, Genetics, Humans, complement, Cytotoxicity, Molecular Biology, 030304 developmental biology, 0303 health sciences, MESH: Humans, biology, MESH: HIV Antibodies, broadly neutralizing antibodies, virus diseases, Complement System Proteins, MESH: HIV Infections, Virology, 3. Good health, Raji cell, Complement system, Lytic cycle, Polyclonal antibodies, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, HIV-1, Antibody, 030217 neurology & neurosurgery
Abstract: International audience; The effect of anti-HIV-1 antibodies on complement activation at the surface of infected cells remains partly understood. Here, we show that a subset of anti-Envelope (Env) broadly neutralizing antibodies (bNAbs), targeting the CD4 binding site and the V3 loop, triggers C3 deposition and complement-dependent cytotoxicity (CDC) on Raji cells engineered to express high surface levels of HIV-1 Env. Primary CD4 T cells infected with laboratory-adapted or primary HIV-1 strains and treated with bNAbs are susceptible to C3 deposition but not to rapid CDC. The cellular protein CD59 and viral proteins Vpu and Nef protect infected cells from CDC mediated by bNAbs or by polyclonal IgGs from HIV-positive individuals. However, complement deposition accelerates the disappearance of infected cells within a few days of culture. Altogether, our results uncover the contribution of complement to the antiviral activity of anti-HIV-1 bNAbs.
Published: 2019

24. Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

Author: Christine Bourgeois, Jennifer Gorwood, Aurélie Barrail-Tran, Claire Lagathu, Jacqueline Capeau, Delphine Desjardins, Roger Le Grand, Abderaouf Damouche, Véronique Béréziat, Olivier Lambotte, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Lipodystrophies, adaptations métaboliques et hormonales, et vieillissement [CRSA], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Microbiology (medical), reservoir, [SDV.IMM] Life Sciences [q-bio]/Immunology, infectious disease, lcsh:QR1-502, Adipose tissue, Review, medicine.disease_cause, Microbiology, Virus, immune response, lcsh:Microbiology, immuneresponse, Mycobacterium tuberculosis, resident memory T cells, 03 medical and health sciences, Immune system, fat, Influenza A virus, medicine, T lymphocyte, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, HIV, Antimicrobial, biology.organism_classification, 3. Good health, adipose tissue, Infectious disease (medical specialty), Immunology, Trypanosoma, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: International audience; Although white AT can contribute to anti-infectious immune responses, it can alsobe targeted and perturbed by pathogens. The AT’s immune involvement is primarilydue to strong pro-inflammatory responses (with both local and paracrine effects),and the large number of fat-resident macrophages. Adipocytes also exert directantimicrobial responses. In recent years, it has been found that memory T cellsaccumulate in AT, where they provide efficient secondary responses against viralpathogens. These observations have prompted researchers to re-evaluate the linksbetween obesity and susceptibility to infections. In contrast, AT serves as a reservoirfor several persistence pathogens, such as human adenovirus Ad-36,Trypanosomagondii,Mycobacterium tuberculosis, influenza A virus, and cytomegalovirus (CMV). Thepresence and persistence of bacterial DNA in AT has led to the concept of a tissue-specific microbiota. The unexpected coexistence of immune cells and pathogens withinthe specific AT environment is intriguing, and its impact on anti-infectious immuneresponses requires further evaluation. AT has been recently identified as a site ofHIV persistence. In the context of HIV infection, AT is targeted by both the virusand the antiretroviral drugs. AT’s intrinsic metabolic features, large overall mass, andwide distribution make it a major tissue reservoir, and one that may contribute to thepathophysiology of chronic HIV infections. Here, we review the immune, metabolic, viral,and pharmacological aspects that contribute to HIV persistence in AT. We also evaluatethe respective impacts of both intrinsic and HIV-induced factors on AT’s involvement asa viral reservoir. Lastly, we examine the potential consequences of HIV persistence onthe metabolic and immune activities of AT.
Published: 2019

25. Virological and immunological impact of integrase inhibitor-based regimens initiated during primary HIV-1 infection

Author: Claudine Duvivier, Raphael Veil, Laurent Cotte, Laure Surgers, Antoine Cheret, Rémonie Seng, Caroline Lascoux Combe, Jacques Reynes, Laurence Meyer, Laurent Tran, David Rey, Clotilde Allavena, Isabelle Poizot-Martin, Pierre Delobel, Cécile Goujard, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), CHU Toulouse [Toulouse], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Paris Cité (UPC), CHU Strasbourg, Sexualité et soins (Genre, Sexualité, Santé) (CESP - INSERM U1018 - Equipe 7), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Saint-Antoine [AP-HP], Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, Sustained Virologic Response, MESH: Sustained Virologic Response, Human immunodeficiency virus (HIV), Integrase inhibitor, MESH: Logistic Models, HIV Infections, MESH: Heterocyclic Compounds, 3-Ring / therapeutic use, medicine.disease_cause, Gastroenterology, Piperazines, Cohort Studies, chemistry.chemical_compound, MESH: Oxazines / therapeutic use, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Medicine, 030212 general & internal medicine, MESH: HIV Integrase Inhibitors / therapeutic use, Darunavir, MESH: Middle Aged, MESH: Pyridones / therapeutic use, Middle Aged, Viral Load, 3. Good health, Infectious Diseases, integrase inhibitors, MESH: HIV Infections / drug therapy, Dolutegravir, Cohort, MESH: HIV Protease Inhibitors / therapeutic use, Female, MESH: Viral Load, Heterocyclic Compounds, 3-Ring, medicine.drug, Cart, Adult, medicine.medical_specialty, Pyridones, Immunology, CD4-CD8 Ratio, MESH: CD4-CD8 Ratio, 03 medical and health sciences, Internal medicine, primary HIV infection, MESH: Cohort Studies Darunavir / therapeutic use, Oxazines, CD4þlymphocyte count, Humans, Protease inhibitor (pharmacology), HIV Integrase Inhibitors, MESH: Humans, business.industry, MESH: Piperazines / therapeutic use, MESH: Adult, HIV Protease Inhibitors, MESH: Male, CD4 Lymphocyte Count, MESH: CD4 Lymphocyte Count, 030104 developmental biology, Logistic Models, chemistry, business, MESH: Female, CD8, CD4þ–CD8þratio, MESH: HIV Infections / immunology
Abstract: International audience; Design: Current international guidelines recommend either boosted protease inhibitor (PI/r)-based or integrase inhibitors (INSTI)-based regimens during primary HIV infection (PHI), even though the latter have only demonstrated their superiority at the chronic stage. We compared the effectiveness of INSTI-based versus PI/r-based combined antiretroviral therapy (cART) initiated during PHI.Methods: This study was conducted among patients who initiated cART between 2013 and 2017, using data from the ANRS-PRIMO cohort and the Dat’AIDS study. Cumulative proportions of patients reaching viral suppression (HIV-1 RNA
Published: 2019

26. Myositis in patients with primary Sjögren’s syndrome: data from a French nationwide survey

Author: Houssais, Camille, Noury, J, Allenbach, Y., Gallay, L, Assan, F, Benveniste, O., Broner, J, Duffau, P, Espitia-Thibault, A, Grasland, A, Sanges, S, Hayem, G., Le Guern, V., Martis, N, Marianpillai, K, Mulleman, D., Nocturne, G., Meyer, A., Devauchelle-Pensec, V., Cornec, D., Guellec, D., Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Neurologie [Brest], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aquitaine’s Care and Research organisation for inflammatory and Immune-Mediated diseases [CHU Bordeaux] (FHU ACRONIM), CHU Bordeaux [Bordeaux], Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, Département de Rhumatologie (Rhumato - Ambroise Paré - PARIS), Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), Hôpital Cochin [AP-HP], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service d'Immunologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Strasbourg, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), 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)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

27. Impact of HIV/simian immunodeficiency virus infection and viral proteins on adipose tissue fibrosis and adipogenesis

Author: Claire Lagathu, Véronique Béréziat, Bruno Fève, Michael Atlan, Valérie Pourcher, Roger Le Grand, Delphine Desjardins, Jennifer Gorwood, Christine Bourgeois, Guillaume Pourcher, Matthieu Mantecon, Olivier Lambotte, Jacqueline Capeau, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Pathologies digestives [Institut Mutualiste Montsouris], Institut Mutualiste de Montsouris (IMM)-Centre de prise en charge de la maladie obésité [Institut Mutualiste Montsouris], Institut Mutualiste de Montsouris (IMM), CHU Saint-Antoine [AP-HP], Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), and CHU Tenon [AP-HP]
Subjects: 0301 basic medicine, Adult, Male, [SDV]Life Sciences [q-bio], Immunology, Extracellular matrix component, Simian Acquired Immunodeficiency Syndrome, Adipose tissue, HIV Infections, Biology, adipogenesis adipose tissue fibrosis mesenchymal stromal cells virus proteins, Gene Products, nef, adipogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Fibrosis, Adipocyte, medicine, Immunology and Allergy, Animals, Humans, Secretion, 030212 general & internal medicine, Cells, Cultured, virus proteins, fibrosis, virus diseases, HIV, Middle Aged, medicine.disease, adipose tissue, Macaca fascicularis, 030104 developmental biology, Infectious Diseases, chemistry, Adipogenesis, Gene Products, tat, Host-Pathogen Interactions, Female, Simian Immunodeficiency Virus, Stem cell, mesenchymal stromal cells
Abstract: Objective HIV-infected patients receiving antiretroviral treatment (ART) often present adipose tissue accumulation and/or redistribution. adipose tissue has been shown to be an HIV/SIV reservoir and viral proteins as Tat or Nef can be released by infected immune cells and exert a bystander effect on adipocytes or precursors. Our aim was to demonstrate that SIV/HIV infection per se could alter adipose tissue structure and/or function. Design Morphological and functional alterations of subcutaneous (SCAT) and visceral adipose tissue (VAT) were studied in SIV-infected macaques and HIV-infected ART-controlled patients. To analyze the effect of Tat or Nef, we used human adipose stem cells (ASCs) issued from healthy donors, and analyzed adipogenesis and extracellular matrix component production using two dimensional (2D) and three-dimensional (3D) culture models. Methods Adipocyte size and index of fibrosis were determined on Sirius red-stained adipose tissue samples. Proliferating and adipocyte 2D-differentiating or 3D-differentiating ASCs were treated chronically with Tat or Nef. mRNA, protein expression and secretion were examined by RT-PCR, western-blot and ELISA. Results SCAT and VAT from SIV-infected macaques displayed small adipocytes, decreased adipogenesis and severe fibrosis with collagen deposition. SCAT and VAT from HIV-infected ART-controlled patients presented similar alterations. In vitro, Tat and/or Nef induced a profibrotic phenotype in undifferentiated ASCs and altered adipogenesis and collagen production in adipocyte-differentiating ASCs. Conclusion We demonstrate here a specific role for HIV/SIV infection per se on adipose tissue fibrosis and adipogenesis, probably through the release of viral proteins, which could be involved in adipose tissue dysfunction contributing to cardiometabolic alterations of HIV-infected individuals.
Published: 2019

28. Higher rates of HBsAg clearance with tenofovir-containing therapy in HBV/HIV co-infection

Author: Pierre Gantner, Laurent Cotte, Clotilde Allavena, Firouzé Bani-Sadr, Thomas Huleux, Claudine Duvivier, Marc-Antoine Valantin, Christine Jacomet, Véronique Joly, Antoine Chéret, Pascal Pugliese, Pierre Delobel, André Cabié, David Rey, Dat’AIDS Study Group, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Gustave Dron [Tourcoing], Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 des Maladies Infectieuses et Tropicales [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Descartes, Sorbonne Paris Cité, Centre Hospitalier Universitaire de Nice (CHU Nice), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU de la Martinique [Fort de France], Université des Antilles (Pôle Martinique), Université des Antilles (UA), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], CHU Strasbourg, The Dat’AIDS Study Group, Hospices Civils de Lyon (HCL), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Université Sorbonne Paris Cité (USPC), Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], Service des maladies infectieuses et tropicales [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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), CHU Clermont-Ferrand, Service des maladies infectieuses et tropicales [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], INSERM 1052, CNRS 5286, CRCL Lyon, Hôpital Gustave Dron [Tourcoing], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service des maladies infectieuses et tropicales[Toulouse], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Gestionnaire, Hal Sorbonne Université
Subjects: Male, HBsAg, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Gastroenterology, Men who have sex with men, MESH: HIV-1, 0302 clinical medicine, MESH: HIV Infections* / blood, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Hepatitis B, Chronic* / blood, 030212 general & internal medicine, MESH: Coinfection* / blood, Multidisciplinary, MESH: Middle Aged, Coinfection, virus diseases, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Hepatitis B Surface Antigens / blood, MESH: Hepatitis B virus, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, MESH: Coinfection* / drug therapy, 030211 gastroenterology & hepatology, Female, MESH: Anti-HIV Agents / administration & dosage, Hiv co infection, Adult, medicine.medical_specialty, Hepatitis B virus, MESH: Hepatitis B, Chronic* / drug therapy, Anti-HIV Agents, Science, 03 medical and health sciences, Hepatitis B, Chronic, Antigen, Internal medicine, medicine, Humans, Seroconversion, Tenofovir, Retrospective Studies, Hepatitis B Surface Antigens, MESH: Humans, business.industry, MESH: Adult, MESH: Retrospective Studies, MESH: HIV Infections* / drug therapy, digestive system diseases, MESH: Male, Regimen, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Tenofovir / administration & dosage, business, MESH: Female
Abstract: IntroductionAchieving functional cure of chronic HBV infection (Hepatitis B surface antigen [HBsAg] clearance, eventually followed by acquisition of anti-hepatitis B surface antigen [Anti-HBs]) in individuals with HIV and HBV infections is a rare event. In this setting, factors related to HBV cure have not yet been fully characterized.MethodsHIV-infected individuals with chronic HBV infection enrolled in the French Dat'AIDS cohort (NCT02898987), who started combined antiretroviral (cART)-anti-HBV treatment were retrospectively analyzed for HBsAg loss and Anti-HBs seroconversion.ResultsOverall, 1419 naïve-subjects received three different cART-anti-HBV treatment schedule: (1) 3TC or FTC only (n = 150), (2) TDF with or without 3TC or FTC (n = 489) and (3) 3TC or FTC as first line followed by adding/switching to TDF as second line (n = 780). Individuals were followed-up for a median of 89 months (IQR, 56-118). HBV-DNA was < 15 IU/mL in 91% of individuals at the end of the follow-up. Overall, 97 individuals cleared HBsAg (0.7/100 patient-years), of whom, 67 seroconverted for Anti-HBs (0.5/100 patient-years). A high CD4 nadir, a short delay between HBV diagnosis and treatment, a longer time on HBV therapy, an African origin and TDF-based therapy were independent predictors of HBsAg clearance (Probability of odds ratio [OR]>1, >95%) suggested by Bayesian analysis. Also, TDF-based regimen as first line (OR, 3.03) or second line (OR, 2.95) increased rates of HBsAg clearance compared to 3TC or FTC alone, with a 99% probability.ConclusionsHBsAg clearance rate was low in HIV-HBV co-infected cART-anti-HBV treated individuals, but was slightly improved on TDF-based regimen.
Published: 2019

29. Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities

Author: Olivier Benveniste, Yves Allenbach, Jacques Cadranel, Ali Manouchehri, Bruno Fautrel, Michelle Rosenzwajg, Bénédicte Lebrun-Vignes, Javid Moslehi, David Klatzmann, Joe-Elie Salem, Stéphane Ederhy, Jean-Philippe Spano, Olivier Lambotte, Céline Anquetil, Douglas B. Johnson, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CIC Paris Est, 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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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 National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [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), Vanderbilt University School of Medicine [Nashville], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), Hôpital Bicêtre, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Neyroud, Nathalie, CCSD, Accord Elsevier, Service de Pharmacologie médicale [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 Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Service de Rhumatologie [CHU Pitié Salpêtrière], Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Centre de Recherche en Myologie, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], 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 Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, medicine.medical_specialty, Myocarditis, [SDV]Life Sciences [q-bio], Immunology, Adverse drug reactions, Arthritis, Polymyalgia rheumatica, Pharmacovigilance, Immune checkpoint inhibitors, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Immunology and Allergy, Adverse effect, Myositis, Retrospective Studies, Pharmacology, 030203 arthritis & rheumatology, business.industry, Bayes Theorem, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Sarcoidosis, business
Abstract: International audience; Background: In addition to restoring anti-tumor immune responses, immune checkpoint inhibitors (ICI) may also induce immune-related adverse events (irAE) that can affect any organ. We aim to determine the spectrum, timing, clinical features, and fatalities of rheumatic and musculoskeletal immune-related adverse events (RMS-irAE) associated with ICI.Patients methods: We performed an observational, retrospective, pharmacovigilance study using the World Health Organization international pharmacovigilance database, VigiBase, from inception to January 2019. RMS-irAE reporting rate on ICI versus full database was performed using disproportionality analysis with computation of reporting-odds-ratios (ROR) and a Bayesian disproportional estimate (information component, IC). IC025 (lower end of the IC 95% credibility interval) >0 is deemed significant.Results: We identified 1288 RMS-irAE significantly associated with ICI: polymyalgia rheumatica (n = 76, ROR = 14.6 [11.6-18.4], IC025 = 3.34), sarcoidosis (n = 94; ROR = 9.6 [7.9-11.9]; IC025 = 2.85), Sjogren's syndrome (n = 49; ROR = 6.9 [5.2-9.2]; IC025 = 2.24), myositis (n = 465; ROR = 4.9 [4.5-5.4]; IC025 = 2.12), arthritis (n = 606; ROR = 1.4 [1.3-1.5]; IC025 = 0.34) and scleroderma (n = 17; ROR = 2.0 [1.2-3.2]; IC025 = 0.17). Arthritis, myositis, and Sjogren's syndrome were over-reported in patients treated with ICI combination versus those treated with ICI monotherapy (ROR = 1.6-2.9, p < .05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p < .05). Median time to onset occurred early for myositis (31 days [19.2-57.8]) and was the most delayed for scleroderma (395 days [323.8-457.2], p < .0001). The fatality rate for RMS-irAE ranged from 24% for myositis (n = 106/441) (up to 56.7% with concurrent myocarditis) to [0-6.7%] for other RMS-irAE (p < .0001).Conclusions: Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis.
Published: 2020

30. Pertinence des inhibiteurs des points de contrôle immunitaire chez les patients atteints de maladie auto-immune ou inflammatoire

Author: Olivier Lambotte, François-Xavier Danlos, Institut Gustave Roussy (IGR), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], General Medicine, General Biochemistry, Genetics and Molecular Biology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2018

31. Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

Author: Pressiat, Claire, Hirt, Déborah, Treluyer, Jean-Marc, Zheng, Yi, Morlat, Philippe, Naqvi, Alice, Tran, Laurent, Viard, Jean-Paul, Avettand-Fenoel, Véronique, Rouzioux, Christine, Meyer, Laurence, Cheret, Antoine, Hoen, B, Bourdeaux, C, Delfraissy, J, Goujard, C, Amri, I, Fourn, E, Quertainmont, Y, Môle, M, Rami, A, Durel, A, Diemer, M, Parrinello, M, Allègre, T, Lafeuillade, A, Hittinger, G, Lambry, V, Carrerre, M, Philip, G, Duvivier, C, Consigny, P, Charlier, C, Shoai, M, Touam, F, Pialoux, G, Slama, L, l'Yavanc, T, Mathurin, P, Adda, A, Berrebi, V, Salmon, D, Chakvetadze, E, Tassadit, T, Ousseima, E, Pietri, M, Levy, Y, Lascaux, A, Lelievre, J, Giovanna, M, Dominguez, S, Dumont, C, Katlama, C, Valentin, M, Seang, S, Schneider, L, Kiorza, N, Chermak, A, Ben Abdallah, S, Simon, A, Pichon, F, Pauchard, M, Molina, J, Lascoux, C, Ponscarme, D, Colin de Verdiere, N, Scemla, A, de Castro, N, Rachline, A, Garrait, V, Rozenbaum, W, Ferret, S, Balkan, S, Clavel, F, Tourdjman, M, Lafaurie, M, Aslan, A, Goguel, J, Thierry, S, de Lastours, V, Gallien, S, Pavie, J, Delgado, J, Mededji, C, Veron, R, Abel, S, Pierre-François, S, Baringhton, C, Chennebault, J, Vandamme, Y, Fialaire, P, Rehaiem, S, Rabier, V, Abgueguen, P, Vandenhende, M, Bernard, N, Lacoste, D, Michaux, C, Paccalin, F, Receveur, M, Caldato, S, Delaune, J, Ragnaud, J, Neau, D, Lacaze-Buzy, L, Livrozet, J, Jeanblanc, F, Makhloufi, D, Brunel Dalmas, F, Jourdain, J, Chiarello, P, Yeni, P, Phung, B, Rioux, C, Godard, C, Louni, F, El Alami Talbi, N, Catalano, G, Guiroy, F, Reynes, J, Jacquet, J, Fauchere, V, Merle, C, Lemoine, V, Loriette, M, Morquin, D, Makinson, A, Atoui, N, Tramoni, C, Raffi, F, Allavena, C, Bonnet, B, Bouchez, S, Feuillebois, N, Brunet-François, C, Reliquet, V, Mounoury, O, Morineau-Le-Houssine, P, Billaud, E, Brosseau, D, Hüe, H, Dellamonica, P, Vassallo, M, Leplatois, A, Durant, J, Joulié, A, Souala, F, Michelet, C, Arvieux, C, Tattevin, P, Leroy, H, Revest, M, Fily, F, Chapplain, J, Ratajczak, C, Gras, G, Bernard, L, Dailloux, J, Laplantine, V, Cuzin, L, Marchou, B, Larrigue, S, Chauveau, M, Balsarin, F, Obadia, M, Bonne, S, Huleux, T, Ajana, F, Alcaraz, I, Baclet, V, Melliez, H, Viget, N, de la Tribonniere, X, Aissi, E, Poissy, J, Ravaux, I, Vallon, A, Varan, M, May, T, Letranchant, L, Burty, C, Briaud, A, Wassoumbou, S, Stenzel, M, Bouillon, M, Debab, Y, Caron, F, Gueit, I, Chapuzet, C, Borsa Lebas, F, Etienne, M, Miailhes, P, Perpoint, T, Senechal, A, Schlienger, I, Cotte, L, Augustin Normand, C, Boibieux, A, Ferry, T, Corsini, N, Braun, E, Lippran, J, Biron, F, Chidiac, C, Pailhes, S, Lipman, J, Koffi, J, Thoirain, V, Brochier, C, Greder Belan, A, Therby, A, Monnier, S, Ruquet, M, Richier, L, Prevoteau Du Clary, F, Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service de Maladies Infectieuses [CHU Nice], Hôpital l'Archet - CHU de Nice, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp] (THERAVIR), 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 National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and CHU Pontchaillou [Rennes]
Subjects: Male, 0301 basic medicine, MESH: Raltegravir Potassium, [SDV]Life Sciences [q-bio], HIV Infections, Pharmacology, Maraviroc, MESH: HIV-1, Plasma, chemistry.chemical_compound, Pharmacology (medical), MESH: Anti-HIV Agents, MESH: Maraviroc, Darunavir, MESH: Darunavir, education.field_of_study, MESH: Middle Aged, MESH: HIV Infections, Middle Aged, Viral Load, Infectious Diseases, MESH: Young Adult, Female, MESH: Viral Load, Viral load, medicine.drug, Adult, Microbiology (medical), Anti-HIV Agents, 030106 microbiology, Population, Emtricitabine, Young Adult, 03 medical and health sciences, Pharmacokinetics, Raltegravir Potassium, medicine, Humans, education, MESH: Plasma, Models, Statistical, Ritonavir, MESH: Humans, business.industry, MESH: Adult, Raltegravir, MESH: Male, 030104 developmental biology, chemistry, HIV-1, MESH: Ritonavir, business, MESH: Female, MESH: Models, Statistical
Abstract: International audience; BackgroundThe OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values
Published: 2018

32. Stage-specific IFN-induced and IFN gene expression reveal convergence of type I and type II IFN and highlight their role in both acute and chronic stage of pathogenic SIV infection

Author: Nadia Echebli, Nicolas Tchitchek, Stéphanie Dupuy, Christine Bourgeois, Roger Le Grand, Benoit Favier, Nathalie Bosquet, Bruno Vaslin, Caroline Peireira Bittencourt Passaes, Rémi Cheynier, Timothée Bruel, Olivier Lambotte, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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 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 Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), This work was supported by the Agence Nationale de Recherches sur le SIDA et les hépatites virales (www.anrs.fr). NE, SD and CPBP benefited from ANRS post-doctoral fellowships. This work was also supported by Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) through research project grant 11360 attributed to BV, by the agence Nationale de la Recherche (http://www.agence-nationale-recherche.fr) 'Programme d’Investissements d’Avenir' (PIA) under Grant ANR-11-INBS-0008, that funds the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure, and PIA grant ANR-10-EQPX-02-01 that funds the FlowCyTech facility (project investigator RLG)., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), Passaes, Caroline, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, and Equipements d'excellence - Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales - - FlowCyTech2010 - ANR-10-EQPX-0002 - EQPX - VALID
Subjects: 0301 basic medicine, RNA viruses, MESH: Interferon Type I, [SDV]Life Sciences [q-bio], lcsh:Medicine, Gene Expression, Monkeys, Pathology and Laboratory Medicine, Biochemistry, Transcriptome, White Blood Cells, 0302 clinical medicine, Immunodeficiency Viruses, Interferon, Animal Cells, Gene expression, Medicine and Health Sciences, MESH: Animals, Cell Cycle and Cell Division, lcsh:Science, Genetic Interference, Mammals, Multidisciplinary, T Cells, Eukaryota, virus diseases, 3. Good health, [SDV] Life Sciences [q-bio], SIV, Medical Microbiology, Cell Processes, 030220 oncology & carcinogenesis, Viral Pathogens, Vertebrates, Viruses, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Pathogens, Anatomy, Cellular Types, MESH: Simian Acquired Immunodeficiency Syndrome, Macaque, medicine.drug, Research Article, Primates, MESH: Gene Expression, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Interferon-gamma, Immune Cells, Immunology, MESH: Simian Immunodeficiency Virus, Biology, Peripheral blood mononuclear cell, Microbiology, Lymphatic System, 03 medical and health sciences, Downregulation and upregulation, Old World monkeys, Retroviruses, medicine, Genetics, Animals, Gene, Microbial Pathogens, Blood Cells, MESH: Transcriptome, MESH: Chronic Disease, lcsh:R, Lentivirus, MESH: Virus Replication, Organisms, Biology and Life Sciences, Proteins, Cell Biology, Chronic infection, 030104 developmental biology, Viral replication, MESH: Macaca fascicularis, Amniotes, lcsh:Q, Interferons, Lymph Nodes
Abstract: 23 Feb 2018: Echebli N, Tchitchek N, Dupuy S, Bruel T, Passaes C, et al. (2018) Correction: Stage-specific IFN-induced and IFN gene expression reveal convergence of type I and type II IFN and highlight their role in both acute and chronic stage of pathogenic SIV infection. PLOS ONE 13(2): e0193629. https://doi.org/10.1371/journal.pone.0193629(corresponding to the second file attached); International audience; Interferons (IFNs) play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon stimulated genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of IFN genes and ISGs in tissues of SIV infected macaques to understand the respective roles of type I and type II IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection and to some extent in rectal biopsies but not in PBMCs. Induction of Type II IFN expression persisted during the chronic phase, in contrast to undetectable induction of type I IFN expression. Global gene expression analysis with a major focus on ISGs revealed that at both acute and chronic infection phases most differentially expressed ISGs were inducible by both type I and type II IFNs and displayed the highest increases, indicating strong convergence and synergy between type I and type II IFNs. The analysis of functional signatures of ISG expression revealed temporal changes in IFN expression patterns identifying phase-specific ISGs. These results suggest that IFN-γ strongly contribute to shape ISG upregulation in addition to type I IFN.
Published: 2018

33. Importance of the patient-physician interaction in assessing acceptability of HIV cure trials

Author: Marie Préau, Patrizia Carrieri, Olivier Lambotte, Marie Suzan-Monti, Christel Protière, Bruno Spire, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), Lissalde, Claire, Aix-Marseille Sciences Economiques (AMSE), École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-Ecole Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), service de Médecine Interne et d'Immunologie Clinique [AP-HP Hôpital Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), and 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)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SHS.ECO]Humanities and Social Sciences/Economies and finances, Human immunodeficiency virus (HIV), [SHS.PSY]Humanities and Social Sciences/Psychology, HIV Infections, medicine.disease_cause, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Clinical Trials as Topic, Physician-Patient Relations, business.industry, Health Policy, 030112 virology, 3. Good health, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract: International audience
Published: 2017

34. Strong Ifitm1 Expression In Cd4 T Cells In Hiv Controllers Is Correlated With Immune Activation

Author: Canoui, Etienne, Noël, Nicolas, Lécuroux, Camille, Boufassa, Faroudy, Sáez-Cirión, Asier, Bourgeois, Christine, Lambotte, Olivier, Group, Anrs Co21 Codex, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Departement d'épidémiologie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Anrs Co21 Codex Study Group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), HIV, Inflammation et persistance, Institut Pasteur [Paris], and Guibert, Marie-Genevieve
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Lymphocyte Activation, HIV Long-Term Survivors, 03 medical and health sciences, Interleukin 21, Antigen, Immunity, medicine, Humans, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Viral Load, Virology, Antigens, Differentiation, Immunity, Innate, CD4 Lymphocyte Count, 030104 developmental biology, Infectious Diseases, Immunology, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Viral load, Immunologic Memory, Immune activation
Abstract: International audience; no abstract
Published: 2017

35. All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus–coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13–HEPAVIH Cohort

Author: Daniel Vittecoq, David Zucman, Laurent Alric, Hugues Aumaitre, Firouzé Bani-Sadr, Julie Chas, Isabelle Poizot-Martin, Anne Simon, Philippe Sogni, Karine Lacombe, Didier Neau, Linda Wittkop, Laure Esterle, François Boué, Stéphanie Dominguez, Cécile Goujard, Camille Gilbert, Anne Gervais, Marc-Antoine Valantin, Caroline Lascoux-Combe, Dominique Salmon, François Dabis, Lionel Piroth, Philippe Morlat, Olivier Bouchaud, Eric Billaud, Eric Rosenthal, Patrick Miailhes, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dynamiques des Réponses immunes - Dynamics of Immune Responses, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Hôpital l'Archet, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des maladies infectieuses et tropicales, 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)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CHU Tenon [AP-HP], Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Université de Bordeaux (UB), Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Foch [Suresnes], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Saint Jean de Perpignan, Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], French National Agency for Research on AIDS and Viral Hepatitis (ANRS). Roche, Schering-Plough, GSK, BMS, and Merck-Serono., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Service des maladies infectieuses et tropicales [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Immunologie [CHU Pitié-Salpétrière], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), AP-HP - Hôpital Antoine Béclère [Clamart], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Lissalde, Claire, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Simeprevir, Liver Cirrhosis, Male, Sofosbuvir, Sustained Virologic Response, HIV Infections, Hepacivirus, medicine.disease_cause, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, Prospective Studies, Middle Aged, virologic response, Hepatitis C, 3. Good health, Infectious Diseases, Treatment Outcome, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, Viral hepatitis, medicine.drug, Microbiology (medical), Ledipasvir, medicine.medical_specialty, Daclatasvir, [SDV.IMM] Life Sciences [q-bio]/Immunology, Hepatitis C virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, direct-acting antiviral treatment, Antiviral Agents, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Ribavirin, medicine, Humans, business.industry, cirrhosis, medicine.disease, Virology, human immunodficiency virus (HIV), Regimen, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, hepatitis C virus (HCV)
Abstract: International audience; BACKGROUND:Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce.METHODS:Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome.RESULTS:We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA
Published: 2016

36. Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study

Author: Caroline Solas, Isabelle Poizot-Martin, Eric Bellissant, Lionel Piroth, Patrizia Carrieri, Jade Ghosn, Marc Bourlière, Philippe Colson, Jean-Michel Molina, Alain Renault, Rodolphe Garraffo, Philippe Halfon, Laurent Alric, Alissa Naqvi, Département de Recherche CLinique, CISIH-Sud, Hôpital Sainte-Marguerite, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Department of clinical and biological pharmacology and pharmacovigilance, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pharmacologie, Hôpital Pasteur [Nice] ( CHU ) -CHU Nice, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Pharmacocinétique et de Toxicologie, Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pharmacologie, Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille ( APHM ), Internal Medicine and Infectious Diseases Department, European Hospital and Alphabio Laboratory, Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Université Paris Descartes - Paris 5 ( UPD5 ), Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Service de Maladies Infectieuses [Nice], Observatoire Régional de la Santé Provence Alpes Côte d'Azur, ORS PACA, Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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 ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Européen [Fondation Ambroise Paré - Marseille], Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Archet 2 [Nice] (CHU), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), French National Agency for Research on AIDS and Viral Hepatitis(ANRS), Jonchère, Laurent, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP)
Subjects: Male, HIV Infections, Hepacivirus, Pharmacology, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, boceprevir, Pharmacology (medical), 030212 general & internal medicine, Univariate analysis, Coinfection, virus diseases, Middle Aged, Recombinant Proteins, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Infectious Diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, Genotype, Proline, direct acting antiviral drug, Antiviral Agents, 03 medical and health sciences, Boceprevir, Internal medicine, Ribavirin, medicine, Humans, Adverse effect, HCV retreatment, business.industry, Interferon-alpha, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Raltegravir, HIV/HCV coinfection, Atazanavir, Regimen, chemistry, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract: International audience; Background: Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment.Objectives: To evaluate the efficacy and safety of this drug regimen and the impact of the addition of boceprevir(BOC) on atazanavir (ATV) or raltegravir (RAL) pharmacokinetic parameters in a subgroup of patients.Methods: In this single-arm phase 2 trial, HIV-1/HCV-genotype-1-coinfected patients received PEGylated-interferonα2b (1.5 μg/kg/week)+ ribavirin (800–1400 mg/day) alone until W4 and with BOC(800 mgTID) until W48. Based on virologic response at W8, the three drugs were stopped or PEGylated-interferon/ribavirin was continued alone until W72. The primary endpoint was SVR at W24 off-therapy (SVR24). Results: 64 patients were included. SVR24 was achieved in 53% of patients (CI90%: 43–63%) and in 90% of previous relapsers. In univariate analysis, SVR24 was associated with response to previous HCV treatment, HCV-1b subtype, HCV-RNA decline, ribavirin-Ctrough at W4, and HCV-RNA at W8 but not to fibrosis score, IL28B genotype, or boceprevir-Ctrough at W8. In multivariate analysis, SVR24 remained associated with response to previous HCV treatment [non-responders versus null responders: OR = 5.0(1.3–20.0); relapsers vs. null responders: OR = 28.8(4.9–169.5)]. HCV treatment was discontinued for adverse events in 17% of patients. A 51% decrease in ATV/r-AUC0–8 h (p \textless 0.01) and a 57% increase in RAL-AUC0–8 h (p \textless 0.01) were observed, although atazanavir/r or raltegravir did not affect BOC-AUC0–8 h significantly. The ATV mean Cthrough fell from 763.8 ng/mL (CI 95%: 230.3–1297.3) without BOC to 507.7 ng/mL (CI 95%: 164–851.4) with BOC.Conclusions: Boceprevir-based regimen demonstrated a high SVR24 rate in treatment-experienced HIV-HCV genotype-1-coinfected relapsers.
Published: 2016

37. Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells

Author: Teunis B. H. Geijtenbeek, Gianfranco Pancino, Günter Weiss, Olivier Lambotte, Paul Kellam, Ralf Gallasch, Cornelia Lass-Flörl, Doris Wilflingseder, Zlatko Trajanoski, Hubert Hackl, Andrea Schroll, Wilfried Posch, Dan Frampton, Asier Sáez-Cirión, Laurence Weiss, Guibert, Marie-Genevieve, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University College of London [London] (UCL), Wellcome Trust Genome Campus, Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), This work was supported by the Austrian Science Fund (grants FWF P22165 and P24598 to D. W., SFB 021 to Z. T., and P25389 to W. P.), the Oesterreichische Nationalbank Anniversary Fund (project 14875 to W. P.), and the Agence Nationale de la Recherche Contre le SIDA et les Hépatites Virales (to A. S.-C.)., Amsterdam institute for Infection and Immunity, Infectious diseases, Experimental Immunology, Innsbruck Medical University [Austria] (IMU), Institut Pasteur [Paris], and HIV, Inflammation et persistance
Subjects: Adult, Male, opsonization, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, CD11c, chemical and pharmacologic phenomena, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, medicine, Immunology and Allergy, Humans, complement, Antigens, 030304 developmental biology, 0303 health sciences, CD11b Antigen, biology, Follicular dendritic cells, CD11b, Cell Differentiation, Complement System Proteins, Dendritic Cells, Middle Aged, MAPK, 3. Good health, CD11c Antigen, Antibody opsonization, Infectious Diseases, Cytokine, Integrin alpha M, Immunology, biology.protein, HIV-1, Th17 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Th17, Ex vivo, 030215 immunology
Abstract: International audience; Early on in human immunodeficiency virus (HIV) type 1 infection, gut T-helper (Th) 17 cells are massively depleted leading eventually to compromised intestinal barrier function and excessive immune activation. In contrast, the functional Th17 cell compartment of the gut is well-maintained in nonpathogenic simian immunodeficiency virus infection as well as HIV-1 long-term nonprogressors. Here, we show that dendritic cells (DCs) loaded with HIV-1 bearing high surface complement levels after incubation in plasma from HIV-infected individuals secreted significantly higher concentrations of Th17-polarizing cytokines than DCs exposed to nonopsonized HIV-1. The enhanced Th17-polarizing capacity of in vitro-generated and BDCA-1(+) DCs directly isolated from blood was linked to activation of ERK. In addition, C3a produced from DCs exposed to complement-opsonized HIV was associated with the higher Th17 polarization. Our in vitro and ex vivo data, therefore, indicate that complement opsonization of HIV-1 strengthens DC-mediated antiviral immune functions by simultaneously triggering Th17 expansion and intrinsic C3 formation via DC activation.
Published: 2015

38. Immunologic and Virologic Progression in HIV Controllers: The Role of Viral 'Blips' and Immune Activation in the ANRS CO21 CODEX Study

Author: Nicolas Noel, Nathalie Lerolle, Camille Lécuroux, Cécile Goujard, Alain Venet, Asier Saez-Cirion, Veronique Avettand-Fenoël, Laurence Meyer, Faroudy Boufassa, Olivier Lambotte, ANRS C021 CODEX Study Group, 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), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), HIV, Inflammation et persistance, Institut Pasteur [Paris], Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nicolas Noel received a PhD fellowship from the Fondation pour la Recherche Médicale (FRM). This work was funded by the Agence Nationale pour la Recherche contre le SIDA (ANRS), INSERM and Paris-Sud University., Saez-Cirion, Asier, 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), APHP, Service de Médecine Interne-Immunologie Clinique, Hôpitaux Universitaires Paris Sud, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Paul Brousse - Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, lcsh:Medicine, HIV Infections, Lymphocyte Activation, HIV Long-Term Survivors, Basal (phylogenetics), Antiretroviral Therapy, Highly Active, medicine, Cytotoxic T cell, Humans, lcsh:Science, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, business.industry, lcsh:R, virus diseases, Middle Aged, Viral Load, Prognosis, Virology, 3. Good health, CD4 Lymphocyte Count, medicine.anatomical_structure, Viral replication, Immunology, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, lcsh:Q, business, Viral load, Immune activation, Research Article
Abstract: International audience; Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.
Published: 2015

39. Natural history of HIV-control since seroconversion

Author: Madec, Y, Boufassa, F, Porter, K, Prins, M, Sabin, C, Monforte, AD, Amornkul, P, Bartmeyer, B, Sannes, M, Venet, A, Lambotte, O, Meyer, L, Garcia-de-Olalla, P, CASCADE Collaboration Eurocoord, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Infectious diseases, Epidemiology and Data Science, Other departments, Experimental Immunology, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Medical Research Council Clinical Trials Unit (MRC CTU), University College of London [London] (UCL), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Research Department of Infection and Population Health [London], Ospedale San Paolo, Partenaires INRAE, International AIDS Vaccine Initiative [San Francisco] (AVI), Robert Koch Institute [Berlin] (RKI), Ullevål University Hospital, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: Adult, Male, medicine.medical_specialty, Canada, Time Factors, Immunology, Viremia, HIV Infections, Kaplan-Meier Estimate, Biology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Risk Factors, Internal medicine, HIV Seropositivity, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Seroconversion, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Proportional Hazards Models, HIV-control, seroconverters, 0303 health sciences, Proportional hazards model, Hazard ratio, Australia, Viral Load, duration of control, medicine.disease, loss of control, Confidence interval, 3. Good health, CD4 Lymphocyte Count, Natural history, Europe, Infectious Diseases, natural history, HIV-1, RNA, Viral, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Viral load
Abstract: OBJECTIVES HIV-controllers spontaneously maintain HIV viremia at an undetectable level. We aimed to describe the delay to control from seroconversion, the duration of control, and risk factors for losing control. METHODS HIV-controllers were identified from a pooled dataset of 24 seroconverter cohorts from Europe, Australia, and Canada (CASCADE). HIV-controllers had at least five consecutive viral loads less than 400/500 copies/ml, while antiretroviral therapy naive, for at least 5 years after seroconversion. End of control was defined as two consecutive viral loads above 2000 copies/ml. Duration of control was described using Kaplan-Meier estimates; factors associated with duration of control were identified using a Cox model. CD4⁺ cell count evolution during control was described using a mixed model. RESULTS Of 9896 eligible seroconverters, we identified 140 (1.4%) HIV-controllers, the largest database of HIV-controllers followed from seroconversion. For 64 with viral load measured within 24 months from seroconversion, median delay to control was 16.7 (interquartile range: 7.8-37.9) months. Probability of maintaining control 20 years after seroconversion was 0.74 [95% confidence interval (CI): 0.64-0.85]. Occurrence of blips followed by return to undetectability did not increase the risk of loss of control [hazard ratio: 0.81 (95% CI: 0.10-6.70)]. However, CD4⁺ cell loss during control was significantly accelerated in individuals with blips. CONCLUSION In most individuals, control occurred rapidly after seroconversion; however, more than 3 years were required to achieve control in 25% of HIV-controllers. Control may be sustained even when CD4⁺ cell levels are below 500 cells/μl, opening important new perspectives to understand the physiopathology underlying control.
Published: 2013

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