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113 results on '"French National Agency for Research on AIDS and Viral Hepatitis"'

1. Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen.

Author

Dimeglio, Chloé, Raymond, Stéphanie, Nicot, Florence, Jeanne, Nicolas, Carcenac, Romain, Lefebvre, Caroline, Izopet, Jacques, and French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group

Subjects
French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Humans, HIV-1, HIV Infections, Treatment Outcome, Antiretroviral Therapy, Highly Active, Viral Load, Drug Resistance, Viral, Genotype, Mutation, Genome, Viral, Female, Male, High-Throughput Nucleotide Sequencing, Rilpivirine, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Genome, Microbiology, Medical Microbiology, Pharmacology and Pharmaceutical Sciences
Abstract

ObjectivesTo determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.Patients and methodsFour hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P  1700 copies/mL and to 50% when the mutational load was > 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8).ConclusionsThere is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of

Published
2019

2. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen.

Author

Raymond, Stéphanie, Nicot, Florence, Pallier, Coralie, Bellecave, Pantxika, Maillard, Anne, Trabaud, Mary Anne, Morand-Joubert, Laurence, Rodallec, Audrey, Amiel, Corinne, Mourez, Thomas, Bocket, Laurence, Beby-Defaux, Agnès, Bouvier-Alias, Magali, Lambert-Niclot, Sidonie, Charpentier, Charlotte, Malve, Brice, Mirand, Audrey, Dina, Julia, Le Guillou-Guillemette, Hélène, Marque-Juillet, Stéphanie, Signori-Schmuck, Anne, Barin, Francis, Si-Mohamed, Ali, Avettand Fenoel, Véronique, Roussel, Catherine, Calvez, Vincent, Saune, Karine, Marcelin, Anne Geneviève, Rodriguez, Christophe, Descamps, Diane, Izopet, Jacques, and French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group

Subjects
French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Humans, HIV-1, HIV Infections, Viral Load, Drug Resistance, Viral, Mutation, Adult, Female, Male, Genetic Variation, Rilpivirine, Drug Resistance, Viral, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

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

Published
2018

5. A New Mechanism of Resistance of Human Immunodeficiency Virus Type 2 to Integrase Inhibitors : A 5-Amino-Acid Insertion in the Integrase C-Terminal Domain

Author

French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO5 HIV-2 Cohort, Le Hingrat, Quentin, Collin, Gilles, Lê, Minh, Peytavin, Gilles, Visseaux, Benoit, Bertine, Mélanie, Tubiana, Roland, Karmochkine, Marina, Valin, Nadia, Collin, Fidéline, Lemaignen, Adrien, Bernard, Louis, Damond, Florence, Matheron, Sophie, Descamps, Diane, and Charpentier, Charlotte

Published
2019

8. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author

French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Raymond, Stéphanie, Nicot, Florence, Pallier, Coralie, Bellecave, Pantxika, Maillard, Anne, Trabaud, Mary Anne, Morand-Joubert, Laurence, Rodallec, Audrey, Amiel, Corinne, Mourez, Thomas, Bocket, Laurence, Beby-Defaux, Agnès, Bouvier-Alias, Magali, Lambert-Niclot, Sidonie, Charpentier, Charlotte, Malve, Brice, Mirand, Audrey, Dina, Julia, Le Guillou-Guillemette, Hélène, Marque-Juillet, Stéphanie, Signori-Schmuck, Anne, Barin, Francis, Si-Mohamed, Ali, Fenoel, Véronique Avettand, Roussel, Catherine, Calvez, Vincent, Saune, Karine, Marcelin, Anne Geneviève, Rodriguez, Christophe, Descamps, Diane, and Izopet, Jacques

Published
2018

9. Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)–Coinfected Patients With High HBV Replication

Author

French National Agency for Research on AIDS and Viral Hepatitis (ANRS) 12136 Temprano and ANRS 12240 VarBVA Study Groups, Kouamé, Gérard-Menan, Boyd, Anders, Moh, Raoul, Badje, Anani, Gabillard, Delphine, Ouattara, Eric, Ntakpe, Jean-Baptiste, Emième, Arlette, Maylin, Sarah, Chekaraou, Mariama Abdou, Eholié, Serge-Paul, Zoulim, Fabien, Lacombe, Karine, Anglaret, Xavier, and Danel, Christine

Published
2018

10. In Utero Exposure to Zidovudine and Heart Anomalies in the ANRS French Perinatal Cohort and the Nested PRIMEVA Randomized Trial

Author

French National Agency for Research on AIDS and Viral Hepatitis French Perinatal Cohort/Protease Inhibitor Monotherapy Evaluation Trial, Sibiude, Jeanne, Le Chenadec, Jérôme, Bonnet, Damien, Tubiana, Roland, Faye, Albert, Dollfus, Catherine, Mandelbrot, Laurent, Delmas, Sandrine, Lelong, Nathalie, Khoshnood, Babak, Warszawski, Josiane, and Blanche, Stéphane

Published
2015

11. Telaprevir for HIV/Hepatitis C Virus–Coinfected Patients Failing Treatment With Pegylated Interferon/Ribavirin (ANRS HC26 TelapreVIH): An Open-Label, Single-Arm, Phase 2 Trial

Author

French National Agency for Research on AIDS and Viral Hepatitis (ANRS) HC26 Study Group, Cotte, Laurent, Braun, Joséphine, Lascoux-Combe, Caroline, Vincent, Corine, Valantin, Marc-Antoine, Sogni, Philippe, Lacombe, Karine, Neau, Didier, Aumaitre, Hugues, Batisse, Dominique, de Truchis, Pierre, Gervais, Anne, Michelet, Christian, Morlat, Philippe, Vittecoq, Daniel, Rosa, Isabelle, Bertucci, Inga, Chevaliez, Stéphane, Aboulker, Jean-Pierre, and Molina, Jean-Michel

Published
2014

12. A New Mechanism of Resistance of Human Immunodeficiency Virus Type 2 to Integrase Inhibitors: A 5-Amino-Acid Insertion in the Integrase C-Terminal Domain.

Author

Hingrat, Quentin Le, Collin, Gilles, Lê, Minh, Peytavin, Gilles, Visseaux, Benoit, Bertine, Mélanie, Tubiana, Roland, Karmochkine, Marina, Valin, Nadia, Collin, Fidéline, Lemaignen, Adrien, Bernard, Louis, Damond, Florence, Matheron, Sophie, Descamps, Diane, Charpentier, Charlotte, and Cohort, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO5 HIV-2

Subjects
HIV infection genetics, RALTEGRAVIR, HIV, HIV infections, MICROBIAL sensitivity tests, MULTIDRUG resistance, GENETIC mutation, PHENOTYPES, TREATMENT effectiveness, GENOTYPES, HIV integrase inhibitors, THERAPEUTICS
Abstract

Background Integrase strand transfer inhibitors (INSTIs) are crucial for the treatment of human immunodeficiency virus (HIV) type 2 infection, due to limited available therapeutic options. Recently, bictegravir has been approved for HIV-1, but no data are currently available for HIV-2. Methods We assessed the phenotypic susceptibility of 12 HIV-2 clinical isolates, obtained from 2 antiretroviral-naive and 10 antiretroviral-experienced patients, to 5 INSTIs (bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir) at the virological failure of an INSTI-based regimen. The 50% inhibitory concentrations (IC50s) were determined. Phenotypic inhibitory quotients were determined using trough INSTI plasma concentrations. Results Wild-type viruses were susceptible to the 5 INSTIs, with IC50s in the nanomolar range. Bictegravir had a lower IC50 than the other INSTIs on those HIV-2 isolates bearing major, resistance-associated mutations (codons 143, 148, and 155). We identified a new resistance profile—a 5–amino-acid insertion at codon 231 of the HIV-2 integrase (231INS)—in 6 patients at the virological failure of a raltegravir-based regimen. Those patients had adequate raltegravir concentrations, but harbored multiresistant viruses with low genotypic susceptibility scores (median = 1.5). This insertion rendered isolates highly resistant to raltegravir and elvitegravir, and moderately resistant to dolutegravir and cabotegravir. Regarding bictegravir, 2 isolates remained susceptible and 2 had a slight increase in IC50 (3- to 5-fold change). Conclusions Our results confirm the potency of INSTI on HIV-2 clinical isolates with wild-type integrase. In addition, we identified a new resistance pathway, 231INS, selected in antiretroviral-experienced patients with multiresistant HIV-2 viruses. This highlights the need of close follow-up of those patients initiating an INSTI-based regimen. [ABSTRACT FROM AUTHOR]

Published
2019
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13. Nonreactive Human Immunodeficiency Virus Type 1 Rapid Tests After Sustained Viral Suppression Following Antiretroviral Therapy Initiation During Primary Infection.

Author

Stefic, Karl, Novelli, Sophie, Mahjoub, Nadia, Seng, Remonie, Molina, Jean-Michel, Cheneau, Christine, Barin, Francis, Chaix, Marie-Laure, Meyer, Laurence, Delaugerre, Constance, and French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO Study Group

Subjects
DIAGNOSIS of HIV infections, HIV infections, THERAPEUTICS, HIV-positive persons, HIGHLY active antiretroviral therapy, ANTIRETROVIRAL agents
Abstract

We assessed the impact of early antiretroviral treatment (ART) on human immunodeficiency virus (HIV) antibody detection by rapid tests in 44 individuals after several years of successful ART. HIV self-tests and point-of-care tests were negative in 30% and 7%-9% of cases, respectively. These data reinforce the message that patients should never be retested after entering HIV care. [ABSTRACT FROM AUTHOR]

Published
2018
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14. Hepatitis e virus infection in sheltered homeless persons, france.

Author

Larrat S, Gaillard S, Baccard M, Piroth L, Cacoub P, Pol S, Perronne C, Carrat F, Morand P, French National Agency for Research on AIDS and viral hepatitis HC02 Ribavic Study Team, Larrat, Sylvie, Gaillard, Stéphanie, Baccard, Monique, Piroth, Lionel, Cacoub, Patrice, Pol, Stanislas, Perronne, Christian, Carrat, Fabrice, and Morand, Patrice

Published
2012
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15. 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
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17. Novel role of UHRF1 in the epigenetic repression of the latent HIV-1

Author

Roxane Verdikt, Maryam Bendoumou, Sophie Bouchat, Lorena Nestola, Alexander O. Pasternak, Gilles Darcis, Véronique Avettand-Fenoel, Caroline Vanhulle, Amina Aït-Ammar, Marion Santangelo, Estelle Plant, Valentin Le Douce, Nadège Delacourt, Aurelija Cicilionytė, Coca Necsoi, Francis Corazza, Caroline Pereira Bittencourt Passaes, Christian Schwartz, Martin Bizet, François Fuks, Asier Sáez-Cirión, Christine Rouzioux, Stéphane De Wit, Ben Berkhout, Virginie Gautier, Olivier Rohr, Carine Van Lint, Université libre de Bruxelles (ULB), University of Amsterdam [Amsterdam] (UvA), Université de Liège, 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 (UPCité), University College Dublin [Dublin] (UCD), Institut Pasteur [Paris] (IP), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA), CVL acknowledges funding from the Belgian National Fund for Scientific Research (F.R.S.-FNRS, Belgium), the « Fondation Roi Baudouin », the NEAT (European AIDS Treatment Network) program, the Internationale Brachet Stiftung, ViiV Healthcare, the Walloon Region (« Fonds de Maturation »), « Les Amis des Instituts Pasteur à Bruxelles, asbl », and the University of Brussels (Action de Recherche Concertée ULB grant) related to her work on HIV latency. The laboratory of CVL is part of the ULB-Cancer Research Center (U-CRC). RV was funded by an 'Aspirant' fellowship (F.R.S-FNRS), a fellowship from 'Les Amis des Instituts Pasteur à Bruxelles, asbl' and is a Belgian American Educational Foundation (BAEF) fellow and a scientific collaborator of the ULB. LN is supported by a 'PDR' grant from the F.R.S-FNRS. GD is a postdoctoral clinical master specialist for the F.R.S-FNRS. A A-A is a fellow of the 'Wallonie-Bruxelles International' Program and the Marie Skłodowska Curie COFUND action. EP is a fellow of the 'Télévie Program' (F.R.S-FNRS). MBD and MS are funded by FRIA fellowships (F.R.S.-FNRS). CVL is 'Directeur de Recherches' at the F.R.S-FNRS. Work in OR's laboratory was supported by grants from the French Agency for Research on AIDS and Viral Hepatitis (ANRS), the Sidaction and the 'Alsace contre le Cancer' Foundation. This work was supported by the European Union's Horizon 2020 research and innovation program under grant agreement No 691119-EU4HIVCURE-H2020-MSCA-RISE-2015. This work is supported by 1UM1AI164562-01, co-funded by National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse and the National Institute of Allergy and Infectious, We thank the members of the ANRS (French National Agency for Research on AIDS and Viral Hepatitis) RHIVIERA (Remission of HIV Era) Consortium for helpful discussions. We thank the HIV-1+ individuals for their willingness to participate in this study. We thank the nursing team of CHU Saint-Pierre Hospital (Elodie Goudeseune, Joëlle Cailleau and Annick Caestecker) who cared for the HIV+ individuals. We thank Jacqueline Pineau from the transfusion centre of Charleroi (Belgium) for providing blood from healthy donors. We thank Hilde Vereertbrugghen from Francis Corazza's laboratory for excellent technical assistance. We thank Motoko Unoki for her precious advice regarding UHRF1 RNA interference. We thank Mitia Duerinckx and Benoît Van Driessche for their support in the probabilistic and statistical analyses., European Project: 691119,H2020,H2020-MSCA-RISE-2015,EU4HIVCURE(2016), Saez-Cirion, Asier, Accelerating HIV Cure in Europe - EU4HIVCURE - - H20202016-02-01 - 2020-01-31 - 691119 - VALID, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies 6041, Belgium, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Amsterdam 1105 AZ, the Netherland, Infectious Diseases Department, Liège University Hospital, Liège 4000, Belgium, Centre for Research in Infectious Diseases, University College Dublin, Dublin 4, Ireland, Service des Maladies Infectieuses, CHU St-Pierre, Université Libre de Bruxelles (ULB), Brussels 1000, Belgium, Laboratory of Immunology, IRISLab, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels 1020, Belgium, Dynamique des interactions hôte pathogène (DIHP), Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels 1070, Belgium, and AP-HP, Hôpital Necker-Enfants-Malades, Service de Microbiologie clinique, Paris 75015, France

Subjects
Ubiquitin-Protein Ligases, Clinical Sciences, HIV Infections, Epigenetic Repression, Decitabine, General Biochemistry, Genetics and Molecular Biology, Genetics, Humans, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, UHRF1, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Acquired Immunodeficiency Syndrome, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, DNA Methylation, Reactivation, Virus Latency, Infectious Diseases, Good Health and Well Being, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, CCAAT-Enhancer-Binding Proteins, Public Health and Health Services, HIV/AIDS, Epigenetics, HIV-1 latency, Infection, EGCG
Abstract

BackgroundThe multiplicity, heterogeneity, and dynamic nature of human immunodeficiency virus type-1 (HIV-1) latency mechanisms are reflected in the current lack of functional cure for HIV-1. Accordingly, all classes of latency-reversing agents (LRAs) have been reported to present variable ex vivo potencies. Here, we investigated the molecular mechanisms underlying the potency variability of one LRA: the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC).MethodsWe employed epigenetic interrogation methods (electrophoretic mobility shift assays, chromatin immunoprecipitation, Infinium array) in complementary HIV-1 infection models (latently-infected T-cell line models, primary CD4+ T-cell models and ex vivo cultures of PBMCs from HIV+ individuals). Extracellular staining of cell surface receptors and intracellular metabolic activity were measured in drug-treated cells. HIV-1 expression in reactivation studies was explored by combining the measures of capsid p24Gag protein, green fluorescence protein signal, intracellular and extracellular viral RNA and viral DNA.FindingsWe uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) to the HIV-1 promoter. We showed that UHRF1 redundantly binds to the HIV-1 promoter with different binding modalities where DNA methylation was either non-essential, essential or enhancing UHRF1 binding. We further demonstrated the role of UHRF1 in the epigenetic repression of the latent viral promoter by a concerted control of DNA and histone methylations.InterpretationA better understanding of the molecular mechanisms of HIV-1 latency allows for the development of innovative antiviral strategies. As a proof-of-concept, we showed that pharmacological inhibition of UHRF1 in ex vivo HIV+ patient cell cultures resulted in potent viral reactivation from latency. Together, we identify UHRF1 as a novel actor in HIV-1 epigenetic silencing and highlight that it constitutes a new molecular target for HIV-1 cure strategies.FundingFunding was provided by the Belgian National Fund for Scientific Research (F.R.S.-FNRS, Belgium), the «Fondation Roi Baudouin», the NEAT (European AIDS Treatment Network) program, the Internationale Brachet Stiftung, ViiV Healthcare, the Télévie, the Walloon Region («Fonds de Maturation»), «Les Amis des Instituts Pasteur à Bruxelles, asbl», the University of Brussels (Action de Recherche Concertée ULB grant), the Marie Skodowska Curie COFUND action, the European Union's Horizon 2020 research and innovation program under grant agreement No 691119-EU4HIVCURE-H2020-MSCA-RISE-2015, the French Agency for Research on AIDS and Viral Hepatitis (ANRS), the Sidaction and the "Alsace contre le Cancer" Foundation. This work is supported by 1UM1AI164562-01, co-funded by National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases.

Published
2022
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18. Metabolic plasticity of HIV-specific CD8+ T cells is associated with enhanced antiviral potential and natural control of HIV-1 infection

Author

Michaela Müller-Trutwin, Mathieu Angin, Laurence Meyer, Roger Le Grand, Olivier Lambotte, Caroline Passaes, Stevenn Volant, Camille Lécuroux, Gianfranco Pancino, Laurence Weiss, Faroudy Boufassa, Jose Carlos Valle-Casuso, Cécile Goujard, Asier Sáez-Cirión, Marie-Agnès Dillies, Bruno Vaslin, Valérie Monceaux, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Biologie François JACOB (JACOB), 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), 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), Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, 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), The present study was conducted with funds from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), MSDAVENIR and the European Union (EU)’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 706871. M.A. received support from the EU (grant no. 706871) and complementary support from Sidaction. C.P. received support from the ANRS. J.C.V.-C. received support from Institut Pasteur through the Roux-Cantarini programme. The ANRS CO6 and CO21 cohorts were sponsored and funded by the ANRS. IDMIT infrastructure was supported by the French government Programme d’Investissements d’Avenir under grant no. ANR-11-INBS-0008., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 706871,H2020,H2020-MSCA-IF-2015,GLUTORHIV(2016), HIV, Inflammation et persistance, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), Saez-Cirion, Asier, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, and Glucose metabolism and mTOR pathway role in CD8+ T cell control of HIV-1 - GLUTORHIV - - H20202016-04-01 - 2018-03-31 - 706871 - VALID

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Population, Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Physiology (medical), Internal Medicine, Cytotoxic T cell, Glycolysis, education, Gene, 030304 developmental biology, 0303 health sciences, education.field_of_study, Cell Biology, In vitro, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, CD8, 030215 immunology
Abstract

International audience; Spontaneous control of human immunodeficiency virus (HIV) is generally associated with an enhanced capacity of CD8+ T cells to eliminate infected CD4+ T cells, but the molecular characteristics of these highly functional CD8+ T cells are largely unknown. In the present study, using single-cell analysis, it was shown that HIV-specific, central memory CD8+ T cells from spontaneous HIV controllers (HICs) and antiretrovirally treated non-controllers have opposing transcriptomic profiles. Genes linked to effector functions and survival are upregulated in cells from HICs. In contrast, genes associated with activation, exhaustion and glycolysis are upregulated in cells from non-controllers. It was shown that HIV-specific CD8+ T cells from non-controllers are largely glucose dependent, whereas those from HICs have more diverse metabolic resources that enhance both their survival potential and their capacity to develop anti-HIV effector functions. The functional efficiency of the HIV-specific CD8+ T cell response in HICs is thus engraved in their memory population and related to their metabolic programme. Metabolic reprogramming in vitro through interleukin-15 treatment abrogated the glucose dependency and enhanced the antiviral potency of HIV-specific CD8+ T cells from non-controllers.

Published
2019
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19. Extracellular vesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation

Author

Corinne Chareyre, Stéphane Robert, Stéphanie Simoncini, Françoise Dignat-George, Aurélie S. Leroyer, Patrice Roll, Olivia Zaegel-Faucher, Luc Lyonnet, Joëlle Micallef, Romaric Lacroix, Estelle Balducci, Isabelle Poizot-Martin, Dilyana Todorova, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Assistance Publique - Hôpitaux de Marseille (APHM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Leroyer, Aurelie, French National Agency for Research on AIDS and Viral Hepatitis, Bartoli, Marc, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, Adult, CD4-Positive T-Lymphocytes, Male, Cell biology, RNase P, T cell, [SDV]Life Sciences [q-bio], lcsh:Medicine, HIV Infections, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Article, Cell Line, Endothelial activation, 03 medical and health sciences, Extracellular Vesicles, 0302 clinical medicine, Downregulation and upregulation, In vivo, microRNA, medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, lcsh:Science, [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, lcsh:R, Endothelial Cells, In vitro, 3. Good health, Up-Regulation, [SDV] Life Sciences [q-bio], MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Case-Control Studies, HIV-1, Female, lcsh:Q, 030217 neurology & neurosurgery, Homeostasis, Cell signalling
Abstract

Human immunodeficiency virus type 1 (HIV-1) infection promotes a generalized activation of host responses that involves not only CD4 T cells, but also cells of the microenvironment, which are not directly infected, such as endothelial cells. The mechanisms triggering HIV-1-associated vascular alterations remain poorly understood. Extracellular vesicles (EVs), implicated in cell-to-cell communication, have been recently described as carriers of microRNAs (miRNAs). Here, we show that miR-146b-5p is upregulated in both CD4 T cells, CD4 T cell-derived EVs and circulating EVs obtained from antiretroviral therapy-naive HIV-1-infected patients. We further demonstrate that EVs from T cell line overexpressing miR-146b-5p mimics (miR-146b-EVs): 1) protect their miRNA cargo from RNase degradation, 2) transfer miR-146b-5p mimics into endothelial cells and 3) reduce endothelial inflammatory responses in vitro and in vivo in the lungs of mice through the downregulation of nuclear factor-κB-responsive molecules. These data advance our understanding on chronic inflammatory responses affecting endothelial homeostasis, in infectious and non-infectious diseases and pave the way for potential new anti-inflammatory strategies.

Published
2019
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20. Direct, indirect and total effect of HIV coinfection on the risk of non-liver-related cancer in hepatitis C virus-infected patients treated by direct-acting antivirals: a mediation analysis

Author

Chalouni, Mathieu, Pol, Stanislas, Sogni, Philippe, Fontaine, Helene, Lacombe, Karine, Lacombe, Jean-Marc, Esterle, Laure, Dorival, Celine, Bourliere, Marc, Bani-Sadr, Firouze, De Ledinghen, Victor, Zucman, David, Larrey, Dominique, Salmon, Dominique, Carrat, Fabrice, Wittkop, Linda, ANRS CO13 HEPAVIH, Anrs C. O. Hepather Cohorts Study Groups, Martinez, V., 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), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Team MORPH3EUS (INSERM U1219 - UB - ISPED), 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)-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), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), INSERM-TRANSFERT [Paris] (IT), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Joseph [Marseille], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), MC was supported by a doctoral award from the French national Agency for Research on Aids and Viral Hepatitis (ANRS: France Recherche Nord & Sud Sida-HIV Hépatites), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Cité (UPC)

Subjects
Sustained Virologic Response, medicine.medical_treatment, MESH: Sustained Virologic Response, HIV Infections, Hepacivirus, medicine.disease_cause, 0302 clinical medicine, Neoplasms, Pharmacology (medical), MESH: Hepacivirus, MESH: Neoplasms, 030212 general & internal medicine, Coinfection, Health Policy, Hazard ratio, virus diseases, Immunosuppression, MESH: HIV Infections, Hepatitis C, 3. Good health, MESH: Hepatitis C, Chronic, Infectious Diseases, Cohort, HCV, 030211 gastroenterology & hepatology, Non-liver-related cancers, MESH: Antiviral Agents, medicine.medical_specialty, Hepatitis C virus, MESH: Mediation Analysis, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Direct-acting antiviral (DAA) treatment, MESH: Hepatitis C, MESH: Humans, Mediation Analysis, business.industry, HIV coinfection, Cancer, Hepatitis C, Chronic, medicine.disease, Confidence interval, Indirect effect, MESH: Coinfection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Metabolic syndrome, business
Abstract

International audience; OBJECTIVES: HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non-liver-related cancers in HCV participants treated with direct-acting antivirals (DAAs). METHODS: Up to four HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to HIV/HCV-coinfected participants from the ANRS CO13 HEPAVIH cohort. Participants were followed from DAA initiation until the occurrence of a non-liver-related cancer. Counterfactual mediation analysis was carried out to estimate the direct (chronic inflammation and immunosuppression), indirect (tobacco and alcohol consumption and metabolic syndrome) and total effect of HIV coinfection on the risk of non-liver-related cancers. RESULTS: 548 HIV/HCV-coinfected and 2016 monoinfected participants were included. Overall, HIV coinfection was associated with a 3.7-fold [95% confidence interval (CI): 1.7-7.0] higher risk of non-liver-related cancers in HCV participants. This increased risk was explained by significant direct effect [hazard ratio (HR) = 3.4, 95% CI: 1.7-6.6] but not indirect effect (HR = 1.1, 95% CI: 0.8-1.5) of HIV coinfection. CONCLUSIONS: In HCV participants treated with DAAs, the direct effect of HIV coinfection, reflecting chronic inflammation and immunosuppression, was associated with a 3.7-fold higher risk of non-liver-related cancer. By contrast, the indirect effect of HIV coinfection, reflecting higher tobacco and alcohol consumption and metabolic dysregulation, was not significantly associated with the risk of non-liver-related cancers.

Published
2021
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21. Comparative Analysis of Hepatitis C Virus NS5A Dynamics and Localization in Assembly-Deficient Mutants

Author

Jean Dubuisson, Laura Riva, Costin-Ioan Popescu, Corentin Spriet, Yves Rouillé, Nicolas Barois, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institute of Biochemistry [Bucharest], Romanian Academy, This research was funded by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and the ANR through ERA-NET Infect-ERA program (ANR-13-IFEC-0002-01). LR was supported by a post-doctoral fellowship co-funded by the University of Liège and the European Union funding Marie Curie BeIPD DG Research-FP7-PEOPLE PCOFUND-GA-2012-600405., ANR-13-IFEC-0002,HCV-ASSEMBLY,Identification of host factors involved in Hepatitis C Virus assembly and characterization of their potential role in vivo(2013), European Project: 600405,EC:FP7:PEOPLE,FP7-PEOPLE-2012-COFUND,BEIPD(2013), Rouillé, Yves, ERA-NET Infect-ERA - Identification of host factors involved in Hepatitis C Virus assembly and characterization of their potential role in vivo - - HCV-ASSEMBLY2013 - ANR-13-IFEC-0002 - IFEC - VALID, Be International Post-Doc - Euregio and Greater Region - BEIPD - - EC:FP7:PEOPLE2013-02-01 - 2019-01-31 - 600405 - VALID, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Plateformes Lilloises en Biologie et Santé - UMS 2014 - US 41 (PLBS)

Subjects
Microbiology (medical), hepatitis C virus, assembly, Viral protein, Hepatitis C virus, viruses, lipid droplets, Mutant, lcsh:Medicine, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, medicine.disease_cause, Virus, Article, 03 medical and health sciences, Viral life cycle, Lipid droplet, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Immunology and Allergy, NS5A, Molecular Biology, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, General Immunology and Microbiology, 030302 biochemistry & molecular biology, lcsh:R, virus diseases, core, NS4B, biochemical phenomena, metabolism, and nutrition, NS5A dynamics, digestive system diseases, 3. Good health, Cell biology, Infectious Diseases, Virion assembly, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract

International audience; The hepatitis C virus (HCV) life cycle is a tightly regulated process, during which structural and non-structural proteins cooperate. However, the interplay between HCV proteins during genomic RNA replication and progeny virion assembly is not completely understood. Here, we studied the dynamics and intracellular localization of non-structural 5A protein (NS5A), which is a protein involved both in genome replication and encapsidation. An NS5A-eGFP (enhanced green fluorescent protein) tagged version of the strain JFH-1-derived wild-type HCV was compared to the corresponding assembly-deficient viruses Δcore, NS5A basic cluster 352–533 mutant (BCM), and serine cluster 451 + 454 + 457 mutant (SC). These analyses highlighted an increase of NS5A motility when the viral protein core was lacking. Although to a lesser extent, NS5A motility was also increased in the BCM virus, which is characterized by a lack of interaction of NS5A with the viral RNA, impairing HCV genome encapsidation. This observation suggests that the more static NS5A population is mainly involved in viral assembly rather than in RNA replication. Finally, NS4B exhibited a reduced co-localization with NS5A and lipid droplets for both Δcore and SC mutants, which is characterized by the absence of interaction of NS5A with core. This observation strongly suggests that NS5A is involved in targeting NS4B to lipid droplets (LDs). In summary, this work contributes to a better understanding of the interplay between HCV proteins during the viral life cycle.

Published
2021
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22. Initiating antiretroviral treatment early in infancy has long-term benefits on the HIV reservoir in late childhood and adolescence

Author

Avettand-Fenoel, Véronique, Lechenadec, Jérôme, Diallo, Mariama Sadjo, Fillion, Marine, Melard, Adeline, Samri, Assia, Dollfus, Catherine, Blanche, Stéphane, Faye, Albert, Amokrane, Kahina, Autran, Brigitte, Buseyne, Florence, Warszawski, Josiane, Frange, Pierre, Study, ANRS-EP59-CLEAC, 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), Université Paris Cité (UPCité), 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), 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 d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Service d'Immunologie et d'Histocompatibilité, 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)-Université Paris Cité (UPCité), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), The ANRS CLEAC study was supported by the ANRS (French National Agency for Research on AIDS and Viral Hepatitis)., The ANRS CLEAC study group: Hôpital Armand Trousseau, Paris: Mary-France Courcoux, Catherine Dollfus, Marie-Dominique Tabone, Geneviève Vaudre, Hôpital Bicêtre, Le Kremlin-Bicêtre: Corinne Fourcade, Josiane Warsazawski, Jérôme Lechenadec, Olivia Dialla, Laura Nailler, Lamya Ait Si Selmi, Isabelle Leymarie, Thierry Wack, Alexandre Hoctin, Razika Feraon-Nanache, Centre hospitalier intercommunal de Créteil: Isabelle Hau, Hôpital Delafontaine, Saint-Denis: Cécile Gakobwa, Hôpital Necker-Enfants Malades, Paris: Véronique Avettand-Fenoël, Stéphane Blanche, Marine Fillion, Pierre Frange, Nizar Mahlaoui, Adeline Mélard,Florence Veber, Marie-Christine Mourey, Maternité Port-Royal, Paris: Valérie Marcou, Hôpital Robert Debré, Paris: Albert Faye, Martine Lévine, Sandrine Richard, Pitié-Salpêtrière, Paris: Brigitte Autran, Assia Samri, Mariama Diallo, Hôpital Saint-Louis: Sophie Caillat-Zucman, Kahina Amokrane, Rayna Ivanova-Derin, Centre hospitalier intercommunal de Villeneuve-Saint-Georges: Anne Chacé, Institut Pasteur Paris: Florence Buseyne, Thomas Montange, Damien Batalie, Ingrid Fert, Asier Saez-Cirion, Valérie Monceaux, Daniel Scott-Algara, ANRS: Lucie Marchand, Delphine Lebrasseur, Axel Levier., Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], 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)-Hôpital Robert Debré-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Buseyne, Florence

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, virus diseases, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, early ART, children, HIV DNA, protective HLA, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, adolescents
Abstract

International audience; BackgroundEarly combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study aims to compare HIV reservoirs in children (5-12 years) and adolescents (13-17 years) who started cART before 6 months (early (E-)group) or after 2 years old (late (L-)group). MethodsThe ANRS-EP59-CLEAC study prospectively enrolled 76 HIV-1 perinatally-infected patients who reached HIV-RNA

Published
2021
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23. Virological failure and antiretroviral resistance among HIV-infected children after five years follow-up in the ANRS 12225-PEDIACAM cohort in Cameroon

Author

Mathurin Cyrille Tejiokem, Angeladine Kenne, Ida Calixte Penda, Francis Ateba Ndongo, Jules Brice Tchatchueng Mbougua, Francis Yuya Septoh, Suzie Tetang Ndiang, Josiane Warszawski, Albert Faye, Paul Alain Tagnouokam-Ngoupo, Sorel Jakpou, Jeannine Eboumbou Ngallè, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Université de Douala, Centre Hospitalier Essos [Yaoundé, Cameroun], Hôpital Laquintinie [Douala, Cameroun], Fondation Chantal Biya (FCB), 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, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-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), and This prospective study is sponsored by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), grants ANRS 12140 and 12225 to MCT.

Subjects
RNA viruses, Male, Pediatrics, [SDV]Life Sciences [q-bio], HIV Infections, Drug resistance, Pathology and Laboratory Medicine, Geographical Locations, Families, chemistry.chemical_compound, 0302 clinical medicine, Immunodeficiency Viruses, Interquartile range, Medicine and Health Sciences, Public and Occupational Health, Cameroon, Prospective Studies, Treatment Failure, 030212 general & internal medicine, Children, Virus Testing, 0303 health sciences, Multidisciplinary, Pharmaceutics, virus diseases, Lamivudine, Viral Load, Vaccination and Immunization, 3. Good health, Medical Microbiology, Viral Pathogens, Rilpivirine, Viruses, Cohort, Medicine, Drug Therapy, Combination, Female, Pathogens, HIV drug resistance, Research Article, Maternal Age, medicine.drug, Adult, medicine.medical_specialty, Nevirapine, Efavirenz, Anti-HIV Agents, Science, Immunology, Antiretroviral Therapy, Microbiology, 03 medical and health sciences, Antiviral Therapy, Drug Therapy, Diagnostic Medicine, Virology, Retroviruses, Drug Resistance, Viral, medicine, Humans, Microbial Pathogens, 030306 microbiology, business.industry, Lentivirus, Organisms, Biology and Life Sciences, HIV, Infant, Infectious Disease Transmission, Vertical, chemistry, Age Groups, People and Places, Africa, HIV-1, Population Groupings, Preventive Medicine, business, Viral Transmission and Infection, Follow-Up Studies
Abstract

Objective In the present study, we aimed to evaluate the virological failure (VF) and drug resistance among treated HIV-infected children after five years follow-up in the ANRS-Pediacam cohort in Cameroon. Methods From November 2007 to October 2011, HIV-infected children born to HIV-infected mothers were included in the ANRS-PEDIACAM study and followed-up for more than 5 years. Plasma viral load (VL) was measured at each visit (every three months until month 24 and every 6 months thereafter). VF was the main outcome and HIV drug resistance test was performed using the ANRS procedures and algorithm. Results Data from 155 children were analyzed. The median age at combination antiretroviral therapy (cART) initiation was 4.2 months (interquartile range (IQR): 3.2–5.8), with 103 (66.5%) children taking LPV/r-containing regimen and 51 (32.9%) children taking NVP. After five years follow-up, 63 (40.6%; CI: 32.9–48.8) children experienced VF. The median duration between cART initiation and VF was 22.1 months (IQR: 11.9–37.1) with a median VL of 4.8 log10 (IQR: 4.0–5.5). Among the 57 children with HIV drug resistance results, 40 (70.2%) had at least one drug resistance mutation. The highest resistance rates (30.4–66.1%) were obtained with Lamivudine; Efavirenz; Nevirapine and Rilpivirine. Conclusions These results show high resistance to NNRTI and emphasize the need of VL and resistance tests for optimal follow-up of HIV-infected people especially children.

Published
2021
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24. TLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women

Author

Jean-Charles Guéry, Jacques Izopet, Asma Essat, Arnoo Shaiykova, Caroline Passaes, Sophie Laffont, Ali Youness, Pascal Azar, Michaela Müller-Trutwin, José E. Mejía, Pierre Delobel, Laurence Meyer, Claire Cenac, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (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), Centre de Physiopathologie Toulouse Purpan (CPTP), 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), Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], HIV, Inflammation et persistance, Institut Pasteur [Paris], Service maladies infectieuses et tropicales [CHU Purpan], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], his work was supported by grants from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS, EP-53 study), Fondation pour la Recherche Médicale (DEQ20180339187), and Conseil Régional Occitanie-Midi-Pyrénées. PA was supported by a fellowship from SIDACTION. MMT received grants from the ANRS and the Fondation Beytout., We gratefully acknowledge support from F. L’Faqihi, A.L. Iscache, and V. Duplan at the flow cytometry facility (CPTP), E. Lhuillier, C. Naylies, A. Emile, and Y. Lippi for DNA sequencing and RNA analyses at the GeT-Purpan and GeT-TRiX facilities, and the technical assistance of M. Requena, M. Cazabat, and R. Carcénac. We also thank Anaïs Bellin-Robert and Guilhem Vazzoler for assistance during plasmid cloning, G. von Heijne and H. Nielsen for comments on SignalP, H. Blanché-Koch for curating the CEPH sample panel, S. Lupold for the Metridia luciferase vector, and W. Chowdhury and S. Chavanas for advice on luciferase assays., 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), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), 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), and Passaes, Caroline

Subjects
0301 basic medicine, Adult, CD4-Positive T-Lymphocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, Viremia, HIV Infections, 03 medical and health sciences, 0302 clinical medicine, medicine, CXCL10, Humans, Allele, ComputingMilieux_MISCELLANEOUS, Innate immune system, business.industry, virus diseases, Interferon-alpha, General Medicine, TLR7, Dendritic Cells, Middle Aged, medicine.disease, Phenotype, 3. Good health, 030104 developmental biology, Toll-Like Receptor 7, 030220 oncology & carcinogenesis, Cohort, Immunology, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Viral load, Research Article
Abstract

International audience; Type I IFN (IFN-I) production by plasmacytoid DCs (pDCs) occurs during acute HIV-1 infection in response to TLR7 stimulation, but the role of pDC-derived IFN-I in controlling or promoting HIV-1 infection is ambiguous. We report here a sex-biased interferogenic phenotype for a frequent single-nucleotide polymorphism of human TLR7, rs179008, displaying an impact on key parameters of acute HIV-1 infection. We show allele rs179008 T to determine lower TLR7 protein abundance in cells from women, specifically — likely by diminishing TLR7 mRNA translation efficiency through codon usage. The hypomorphic TLR7 phenotype is mirrored by decreased TLR7-driven IFN-I production by female pDCs. Among women from the French ANRS PRIMO cohort of acute HIV-1 patients, carriage of allele rs179008 T associated with lower viremia, cell-associated HIV-1 DNA, and CXCL10 (IP-10) plasma concentrations. RNA viral load was decreased by 0.85 log10 (95% CI, −1.51 to −0.18) among T/T homozygotes, who also exhibited a lower frequency of acute symptoms. TLR7 emerges as an important control locus for acute HIV-1 viremia, and the clinical phenotype for allele rs179008 T, carried by 30%–50% of European women, supports a beneficial effect of toning down TLR7-driven IFN-I production by pDCs during acute HIV-1 infection.

Published
2020
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25. Patient-reported symptoms during direct-acting antiviral treatment: A real-life study in HIV-HCV coinfected patients (ANRS CO13 HEPAVIH)

Author

Fabienne Marcellin, Vincent Di Beo, Hugues Aumaitre, Marion Mora, Linda Wittkop, Claudine Duvivier, Camelia Protopopescu, Karine Lacombe, Laure Esterle, Cyril Berenger, Camille Gilbert, Olivier Bouchaud, Isabelle Poizot-Martin, Philippe Sogni, Dominique Salmon-Ceron, Patrizia Carrieri, D. Salmon, L. Wittkop, P. Sogni, L. Esterle, P. Trimoulet, J. Izopet, L. Serfaty, V. Paradis, B. Spire, P. Carrieri, M.A. Valantin, G. Pialoux, J. Chas, I. Poizot-Martin, K. Barange, A. Naqvi, E. Rosenthal, A. Bicart-See, O. Bouchaud, A. Gervais, C. Lascoux-Combe, C. Goujard, K. Lacombe, C. Duvivier, D. Neau, P. Morlat, F. Bani-Sadr, L. Meyer, F. Boufassa, B. Autran, A.M. Roque, C. Solas, H. Fontaine, D. Costagliola, L. Piroth, A. Simon, D. Zucman, F. Boué, P. Miailhes, E. Billaud, H. Aumaître, D. Rey, G. Peytavin, V. Petrov-Sanchez, D. Lebrasseur-Longuet, R. Usubillaga, B. Terris, P. Tremeaux, C. Katlama, H. Stitou, P. Cacoub, S. Nafissa, Y. Benhamou, F. Charlotte, S. Fourati, O. Zaegel, H. Laroche, C. Tamalet, P. Callard, F. Bendjaballah, C. Amiel, C. Le Pendeven, B. Marchou, L. Alric, S. Metivier, J. Selves, F. Larroquette, V. Rio, J. Haudebourg, M.C. Saint-Paul, A. De Monte, V. Giordanengo, C. Partouche, A. Martin, M. Ziol, Y. Baazia, V. Iwaka-Bande, A. Gerber, M. Uzan, D. Garipuy, M.J. Ferro-Collados, F. Nicot, Y. Yazdanpanah, H. Adle-Biassette, G. Alexandre, J.M. Molina, P. Bertheau, M.L. Chaix, C. Delaugerre, S. Maylin, J. Bottero, J. Krause, P.M. Girard, D. Wendum, P. Cervera, J. Adam, C. Viala, D. Vittecocq, Y. Quertainmont, E. Teicher, C. Pallier, O. Lortholary, C. Rouzaud, J. Lourenco, F. Touam, C. Louisin, V. Avettand-Fenoel, E. Gardiennet, A. Mélard, A. Ochoa, E. Blanchard, S. Castet-Lafarie, C. Cazanave, D. Malvy, M. Dupon, H. Dutronc, F. Dauchy, L. Lacaze-Buzy, A. Desclaux, P. Bioulac-Sage, S. Reigadas, D. Lacoste, F. Bonnet, N. Bernard, M. Hessamfar, J, F. Paccalin, C. Martell, M.C. Pertusa, M. Vandenhende, P. Mercié, T. Pistone, M.C. Receveur, M. Méchain, P. Duau, C. Rivoisy, I. Faure, S. Caldato, P. Bellecave, C. Tumiotto, J.L. Pellegrin, J.F. Viallard, E. Lazzaro, C. Greib, C. Majerholc, M. Brollo, E. Farfour, J. Polo Devoto, I. Kansau, V. Chambrin, C. Pignon, L. Berroukeche, R. Fior, V. Martinez, S. Abgrall, M. Favier, C. Deback, Y. Lévy, S. Dominguez, J.D. Lelièvre, A.S. Lascaux, G. Melica, F. Raffi, C. Allavena, V. Reliquet, D. Boutoille, C. Biron, M. Lefebvre, N. Hall, S. Bouchez, A. Rodallec, L. Le Guen, C. Hemon, D. Peyramond, C. Chidiac, F. Ader, F. Biron, A. Boibieux, L. Cotte, T. Ferry, T. Perpoint, J. Koffi, F. Zoulim, F. Bailly, P. Lack, M. Maynard, S. Radenne, M. Amiri, F. Valour, C. Augustin-Normand, C. Scholtes, T.T. Le-Thi, P. Chavanet, M. Duong Van Huyen, M. Buisson, A. Waldner-Combernoux, S. Mahy, R. Binois, A.L. Simonet-Lann, D. Croisier-Bertin, A. Salmon Rousseau, C. Martins, S. Galim, D. Lambert, Y. Nguyen, J.L. Berger, M. Hentzien, V. Brodard, M. Partisani, M.L. Batard, C. Cheneau, M. Priester, C. Bernard-Henry, E. de Mautort, P. Gantner et S Fafi-Kremer, F. Roustant, P. Platterier, I. Kmiec, L. Traore, S. Lepuil, S. Parlier, V. Sicart-Payssan, E. Bedel, S. Anriamiandrisoa, C. Pomes, M. Mole, C. Bolliot, P. Catalan, M. Mebarki, A. Adda-Lievin, P. Thilbaut, Y. Ousidhoum, F.Z. Makhoukhi, O. Braik, R. Bayoud, C. Gatey, M.P. Pietri, V. Le Baut, R. Ben Rayana, D. Bornarel, C. Chesnel, D. Beniken, M. Pauchard, S. Akel, C. Lions, A. Ivanova, A.-S. Ritleg, C. Debreux, L. Chalal, J. Zelie, H. Hue, A. Soria, M. Cavellec, S. Breau, A. Joulie, P. Fisher, S. Gohier, S. Ogoudjobi, C. Brochier, V. Thoirain-Galvan, M. Le Cam, M. Chalouni, V. Conte, L. Dequae-Merchadou, M. Desvallees, C. Gilbert, S. Gillet, R. Knight, T. Lemboub, F. Marcellin, L. Michel, M. Mora, C. Protopopescu, P. Roux, S. Tezkratt, T. Barré, M. Baudoin, M. Santos, V. Di Beo, M. Nishimwe, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Centre Hospitalier Saint Jean de Perpignan, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Team MORPH3EUS (INSERM U1219 - UB - ISPED), 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)-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), Pôle de Santé publique [Bordeaux], CHU Bordeaux [Bordeaux], 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), 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), 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), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de maladies infectieuses et tropicales [CHU Avicenne], Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was sponsored and funded by the French National Agency for Research on Aids and Viral Hepatitis (ANRS)., ANRS CO13 HEPAVIH Study Group : : D Salmon, L Wittkop, P Sogni, L Esterle, P Trimoulet, J Izopet, L Serfaty, V Paradis, B Spire, P Carrieri, M A Valantin, G Pialoux, J Chas, I Poizot-Martin, K Barange, A Naqvi, E Rosenthal, A Bicart-See, O Bouchaud, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, C Duvivier, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, B Autran, A M Roque, C Solas, H Fontaine, D Costagliola, L Piroth, A Simon, D Zucman, F Boué, P Miailhes, E Billaud, H Aumaître, D Rey, G Peytavin, V Petrov-Sanchez, D Lebrasseur-Longuet, D Salmon, R Usubillaga, P Sogni, B Terris, P Tremeaux, C Katlama, M A Valantin, H Stitou, A Simon, P Cacoub, S Nafissa, Y Benhamou, F Charlotte, S Fourati, I Poizot-Martin, O Zaegel, H Laroche, C Tamalet, G Pialoux, J Chas, P Callard, F Bendjaballah, C Amiel, C Le Pendeven, B Marchou, L Alric, K Barange, S Metivier, J Selves, F Larroquette, E Rosenthal, A Naqvi, V Rio, J Haudebourg, M C Saint-Paul, A De Monte, V Giordanengo, C Partouche, O Bouchaud, A Martin, M Ziol, Y Baazia, V Iwaka-Bande, A Gerber, M Uzan, A Bicart-See, D Garipuy, M J Ferro-Collados, J Selves, F Nicot, A Gervais, Y Yazdanpanah, H Adle-Biassette, G Alexandre, G Peytavin, C Lascoux-Combe, J M Molina, P Bertheau, M L Chaix, C Delaugerre, S Maylin, K Lacombe, J Bottero, J Krause, P M Girard, D Wendum, P Cervera, J Adam, C Viala, D Vittecocq, C Goujard, Y Quertainmont, E Teicher, C Pallier, O Lortholary, C Duvivier, C Rouzaud, J Lourenco, F Touam, C Louisin, V Avettand-Fenoel, E Gardiennet, A Mélard, D Neau, A Ochoa, E Blanchard, S Castet-Lafarie, C Cazanave, D Malvy, M Dupon, H Dutronc, F Dauchy, L Lacaze-Buzy, A Desclaux, P Bioulac-Sage, P Trimoulet, S Reigadas, P Morlat, D Lacoste, F Bonnet, N Bernard, M Hessamfar J, F Paccalin, C Martell, M C Pertusa, M Vandenhende, P Mercié, D Malvy, T Pistone, M C Receveur, M Méchain, P Duau, C Rivoisy, I Faure, S Caldato, P Bioulac-Sage, P Trimoulet, S Reigadas, P Bellecave, C Tumiotto, J L Pellegrin, J F Viallard, E Lazzaro, C Greib, P Bioulac-Sage, P Trimoulet, S Reigadas, D Zucman, C Majerholc, M Brollo, E Farfour, F Boué, J Polo Devoto, I Kansau, V Chambrin, C Pignon, L Berroukeche, R Fior, V Martinez, S Abgrall, M Favier, C Deback, Y Lévy, S Dominguez, J D Lelièvre, A S Lascaux, G Melica, E Billaud, F Raffi, C Allavena, V Reliquet, D Boutoille, C Biron, M Lefebvre, N Hall, S Bouchez, A Rodallec, L Le Guen, C Hemon, P Miailhes, D Peyramond, C Chidiac, F Ader, F Biron, A Boibieux, L Cotte, T Ferry, T Perpoint, J Koffi, F Zoulim, F Bailly, P Lack, M Maynard, S Radenne, M Amiri, F Valour, J Koffi, F Zoulim, F Bailly, P Lack, M Maynard, S Radenne, C Augustin-Normand, C Scholtes, T T Le-Thi, L Piroth, P Chavanet, M Duong Van Huyen, M Buisson, A Waldner-Combernoux, S Mahy, R Binois, A L Simonet-Lann, D Croisier-Bertin, A Salmon Rousseau, C Martins, H Aumaître, S Galim, F Bani-Sadr, D Lambert, Y Nguyen, J L Berger, M Hentzien, V Brodard, D Rey, M Partisani, M L Batard, C Cheneau, M Priester, C Bernard-Henry, E de Mautort, P Gantner Et S Fafi-Kremer, F Roustant, P Platterier, I Kmiec, L Traore, S Lepuil, S Parlier, V Sicart-Payssan, E Bedel, S Anriamiandrisoa, C Pomes, F Touam, C Louisin, M Mole, C Bolliot, P Catalan, M Mebarki, A Adda-Lievin, P Thilbaut, Y Ousidhoum, F Z Makhoukhi, O Braik, R Bayoud, C Gatey, M P Pietri, V Le Baut, R Ben Rayana, D Bornarel, C Chesnel, D Beniken, M Pauchard, S Akel, S Caldato, C Lions, A Ivanova, A-S Ritleg, C Debreux, L Chalal, J Zelie, H Hue, A Soria, M Cavellec, S Breau, A Joulie, P Fisher, S Gohier, D Croisier-Bertin, S Ogoudjobi, C Brochier, V Thoirain-Galvan, M Le Cam, P Carrieri, M Chalouni, V Conte, L Dequae-Merchadou, M Desvallees, L Esterle, C Gilbert, S Gillet, R Knight, T Lemboub, F Marcellin, L Michel, M Mora, C Protopopescu, P Roux, B Spire, S Tezkratt, T Barré, M Baudoin, M Santos, V Di Beo, M Nishimwe, L Wittkop., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dupuis, Christine

Subjects
MESH: Antiviral Agents, medicine.medical_specialty, simeprevir + ribavirin (1). CI, [SDV]Life Sciences [q-bio], MEDLINE, sofosbuvir + simeprevir (3), HIV Infections, MESH: Patient Reported Outcome Measures, Antiviral Agents, sofosbuvir + ribavirin (4), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, MORPH3Eus, Humans, Patient Reported Outcome Measures, 030212 general & internal medicine, Antiviral treatment, ComputingMilieux_MISCELLANEOUS, MESH: Hepatitis C, MESH: Humans, Hepatology, Coinfection, business.industry, ledipasvir/sofosbuvir (49), ledipasvir/sofosbuvir + ribavirin (10), Hepatitis C, MESH: HIV Infections, Hepatitis C, Chronic, medicine.disease, 3. Good health, MESH: Coinfection, MESH: Hepatitis C, Chronic, [SDV] Life Sciences [q-bio], confidence interval, daclatasvir + sofosbuvir + ribavirin (5), 030211 gastroenterology & hepatology, Life study, business, ombitasvir/ paritaprevir/ritonavir + ribavirin (1), Direct acting, daclatasvir + sofosbuvir (32)
Abstract

International audience; No abstract available

Published
2020
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26. What do the Universal Test and Treat Trials tell us about the path to HIV epidemic control?

Author

Sarah Fidler, Richard J. Hayes, Joseph Larmarange, Diane V. Havlir, François Dabis, Moses R. Kamya, Sian Floyd, Tendani Gaolathe, Janet Moore, Shahin Lockman, Gabriel Chamie, Collins Iwuji, Helen Ayles, Maya L. Petersen, National Institutes of Health, University of California (UC), Botswana Harvard AIDS Institute Partnership, Harvard School of Public Health, London School of Hygiene and Tropical Medicine (LSHTM), Zambart, Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Santé, vulnérabilités et relations de genre au sud (SAGESUD - ERL Inserm U1244), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)-Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Brighton and Sussex Medical School (BSMS), Imperial College London, Makerere University [Kampala, Ouganda] (MAK), University of California [Berkeley] (UC Berkeley), 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), President's Emergency Plan for AIDS Relief, Gilead Sciences, Bill and Melinda Gates Foundation, French National Agency for Research on AIDS and Viral Hepatitis, Deutsche Gesellschaft fur Internationale Zusammenarbeit, Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), and School of Public Health

Subjects
Male, ZAMBIE, HIV elimination, Hiv epidemic, Psychological intervention, HIV Infections, universal access, INITIATION, South Africa, 0302 clinical medicine, OUGANDA, INFECTION, AFRIQUE SUBSAHARIENNE, Prevalence, Medicine, Mass Screening, Uganda, 030212 general & internal medicine, education.field_of_study, Botswana, Incidence (epidemiology), Incidence, public health, AIDS Serodiagnosis, Viral Load, 3. Good health, HIV testing, Infectious Diseases, Female, 0305 other medical science, Viral load, Life Sciences & Biomedicine, 052, 050, 056, AFRICA, Adult, medicine.medical_specialty, Adolescent, Anti-HIV Agents, Population, Immunology, antiretroviral therapy, HIV prevention, Zambia, World health, Time-to-Treatment, 1117 Public Health and Health Services, IDLIC, 03 medical and health sciences, HIV care continuum, Humans, education, Epidemics, AFRIQUE DU SUD, 030505 public health, Science & Technology, business.industry, Public health, Public Health, Environmental and Occupational Health, 1103 Clinical Sciences, Kenya, (Universal Test, Treat Trials) UT3 Consortium, Test and treat, Commentary, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography, 1199 Other Medical and Health Sciences
Abstract

Author(s): Havlir, Diane; Lockman, Shahin; Ayles, Helen; Larmarange, Joseph; Chamie, Gabriel; Gaolathe, Tendani; Iwuji, Collins; Fidler, Sarah; Kamya, Moses; Floyd, Sian; Moore, Janet; Hayes, Richard; Petersen, Maya; Dabis, Francois; (Universal Test, Treat Trials) UT3 Consortium | Abstract: IntroductionAchieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan African(SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign.DiscussionThese three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved g90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted innmarked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in whichnmortality was comprehensively measured.ConclusionsThese trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

Published
2020
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27. Changements de pratiques d'injection de drogues supervisées à la suite d'une intervention éducationnelle communautaire : une analyse longitudinale

Author

Marie Debrus, Patrizia Carrieri, Salim Mezaache, Daniel Rojas Castro, Perrine Roux, Stéphane Morel, Camelia Protopopescu, Marie Suzan-Monti, Marion Mora, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Médecins du Monde [Paris, France] (Association médicale militante de solidarité internationale), AIDES [Pantin, France], Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Coalition PLUS [Pantin, France], and This study received external funding from the French National Agency for Research for AIDS and Viral Hepatitis (ANRS).

Subjects
Adult, Male, medicine.medical_specialty, Hand washing, 030508 substance abuse, Intervention, Toxicology, Drug injecting, Education, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), Humans, Medicine, Pharmacology (medical), Longitudinal Studies, 030212 general & internal medicine, Substance Abuse, Intravenous, Health Education, Pharmacology, Community based, Harm reduction, business.industry, Skin and soft tissue infections, Odds ratio, Middle Aged, Checklist, Confidence interval, 3. Good health, Needle-Exchange Programs, Psychiatry and Mental health, Family medicine, Injecting drug use, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Independent Living, Injecting practices, 0305 other medical science, business
Abstract

Background People who inject drugs face several health issues because of unsafe injecting practices. We aimed to evaluate changes in supervised drug-injecting practices following the implementation of a face-to-face educational intervention. Methods The national study ANRS-AERLI was conducted in 17 harm reduction (HR) facilities in France between 2011 and 2013. Eight offered the intervention and nine did not. We conducted a pre-post analysis focusing on injecting practices data, collected in the 8 HR facilities providing the intervention. The intervention consisted of providing face-to-face educational sessions including direct observation of injecting practices, counseling about safer injecting, and shared discussion. Injecting practices were collected following a checklist and classified as safe or unsafe. To assess changes in injecting practices, practices were compared before (at baseline) and after at least one educational session. Findings Mixed logistic models showed that the 78 participants included were more likely to improve in the following drug-use steps: setting up a clean preparation area (Adjusted Odds Ratio (AOR) = 3.4, 95% Confidence Interval (95% CI) = 1.6–7.6), hand washing (AOR = 7.2, 95% CI = 3.1–16.4), skin cleaning (AOR = 5.6, 95% CI = 2.5–12.1), choice of safe injection site (AOR = 6.5, 95% CI = 1.5–28.8) and post-injection bleeding management (AOR = 12.8, 95% CI = 5.5–29.9). Furthermore, participants were less likely to lick their needles before injecting (AOR = 8.1, 95% CI = 1.5–43.4) and to perform booting/flushing (AOR = 2.5, 95% CI = 1.2–5.3). Conclusions The AERLI intervention seems to be effective in increasing safe drug-injecting practices.

Published
2018
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28. Assessement of Awareness of, Concerns and Attitudes Towards HIV-Related Court-Case Sentences in France in a Representative Sample of People Living with HIV (ANRS VESPA2 Survey)

Author

Marie Suzan-Monti, Bruno Spire, Antoine Vilotitch, Rosemary Dray-Spira, Patrick Yeni, Michel Celse, Baptiste Demoulin, Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), 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), Conseil national du sida et des hépatites virales [Paris, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7), 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), The VESPA2 survey was sponsored and funded by the French National Agency for Research on Aids and Viral Hepatitis (ANRS), Grant No. 2010-176., ANRS VESPA2 study group : Lert F, Spire B, Carrieri P, Dray-Spira R, Hamelin C, Lorente N, Préau M, Suzan-Monti M, Mora M, Le Strat Y, Cuzin L, Meyer L, Rojas-Castro D, Fischer H, Allègre T, Mours P, Riou JM, Sordage M, Chennebault JM, Fialaire P, Rabier V, Froidure M, Huguet D, Leduc D, Pichancourt G, Wajsbrot A, Bourdeaux C, Foltzer A, Hoen B, Hustache-Mathieu L, Abgrall S, Barruet R, Bouchaud O, Chabrol A, Mattioni S, Mechai F, Jeantils V, Bernard N, Bonnet F, Hessamfar M, Lacoste D, Malvy D, Mercié P, Morlat P, Paccalin F, Pertusa MC, Pistone T, Receveur MC, Vandenhende MA, Dupont C, Freire Maresca A, Leporrier J, Rouveix E, Dargere S, de la Blanchardière A, Martin A, Noyon V, Verdon R, Rogeaux O, Beytout J, Gourdon F, Laurichesse H, Meier F, Mortier E, Simonpoli AM, Cordier F, Delacroix I, Garrait V, Elharrar B, Dominguez S, Lascaux AS, Lelièvre JD, Levy Y, Melica G, Buisson M, Piroth L, Waldner A, Gruat N, Leprêtre A, de Truchis P, Le Du D, Melchior JC, Sehouane R, Troisvallets D, Blanc M, Boccon-Gibod I, Bosseray A, Brion JP, Durand F, Leclercq P, Marion F, Pavese P, Brottier-Mancini E, Faba L, Roncato-Saberan M, Bollengier-Stragier O, Esnault JL, Leautez-Nainville S, Perré P, Froguel E, Nguessan M, Simon P, Colardelle P, Doll J, Godin-Collet C, Roussin-Bretagne S, Delfraissy JF, Duracinsky M, Goujard C, Peretti D, Quertainmont Y, Marionneau J, Aissi E, Van Grunderbeeck N, Denes E, Ducroix-Roubertou S, Genet C, Weinbreck P, Augustin-Normand C, Boibieux A, Cotte L, Ferry T, Koffi J, Miailhes P, Perpoint T, Peyramond D, Schlienger I, Brunel JM, Carbonnel E, Chiarello P, Livrozet JM, Makhloufi D, Dhiver C, Husson H, Madrid A, Ravaux I, de Severac ML, Thierry Mieg M, Tomei C, Hakoun S, Moreau J, Mokhtari S, Soavi MJ, Faucher O, Ménard A, Orticoni M, Poizot-Martin I, Atoui N, Baillat V, Faucherre V, Favier C, Jacquet JM, Le Moing V, Makinson A, Mansouri R, Merle C, Elforzli N, Allavena C, Aubry O, Besnier M, Billaud E, Bonnet B, Bouchez S, Boutoille D, Brunet C, Feuillebois N, Lefebvre M, Morineau-Le Houssine P, Mounoury O, Point P, Raffi F, Reliquet V, Talarmin JP, Ceppi C, Cua E, Dellamonica P, De Salvador-Guillouet F, Durant J, Ferrando S, Mondain-Miton V, Perbost I, Pillet S, Prouvost-Keller B, Pradier C, Pugliese P, Rahelinirina V, Roger PM, Rosenthal E, Sanderson F, Hocqueloux L, Niang M, Prazuck T, Arsac P, Barrault-Anstett MF, Ahouanto M, Bouvet E, Castanedo G, Charlois-Ou C, Dia Kotuba A, Eid-Antoun Z, Jestin C, Jidar K, Joly V, Khuong-Josses MA, Landgraf N, Landman R, Lariven S, L'hériteau F, Machado M, Matheron S, Michard F, Morau G, Pahlavan G, Phung BC, Prévot MH, Rioux C, Yéni P, Bani-Sadr F, Calboreanu A, Chakvetadze E, Salmon D, Silbermann B, Batisse D, Beumont M, Castiel P, Derouineau J, Eliaszewicz M, Gonzalez G, Jayle D, Karmochkine M, Kousignian P, Pavie J, Pierre I, Weiss L, Badsi E, Bendenoun M, Cervoni J, Diemer M, Durel A, Rami A, Sellier P, Ait-Mohand H, Amirat N, Bonmarchand M, Bourdillon F, Breton G, Caby F, Grivois JP, Katlama C, Kirstetter M, Paris L, Pichon F, Roudière L, Schneider L, Samba MC, Seang S, Simon A, Stitou H, Tubiana R, Valantin MA, Bollens D, Bottero J, Bui E, Campa P, Fonquernie L, Fournier S, Girard PM, Goetschel A, Guyon HF, Lacombe K, Lallemand F, Lefebvre B, Maynard JL, Meyohas MC, Ouazene Z, Pacanowski J, Picard O, Raguin G, Roussard P, Tourneur M, Tredup J, Valin N, Balkan S, Clavel F, de Verdière NC, De Castro N, de Lastours V, Ferret S, Gallien S, Gérard L, Goguel J, Lafaurie M, Lascoux-Combe C, Molina JM, Oksenhendler E, Pintado C, Ponscarme D, Rozenbaum W, Scemla A, Bonnard P, Lassel L, Lebrette MG, Lyavanc T, Mariot P, Missonnier R, Ohayon M, Pialoux G, Treilhou MP, Vincensini JP, Gilquin J, Hadacek B, Nait-Ighil L, Nguyen TH, Sobel A, Viard JP, Zak Dit Zbar O, Aumaître H, Eden A, Ferreyra M, Lopez F, Medus M, Neuville S, Saada M, Blum L, Perfezou P, Arvieux C, Chapplain JM, Revest M, Souala F, Tattevin P, Bord S, Borsa-Lebas F, Caron F, Chapuzet C, Debab Y, Gueit I, Etienne M, Fartoukh C, Feltgen K, Joly C, Robaday-Voisin S, Suel P, Khuong MA, Krausse J, Poupard M, Tran Van G, Cazorla C, Daoud F, Fascia P, Frésard A, Guglielminotti C, Lucht F, Bernard-Henry C, Cheneau C, Lang JM, de Mautort E, Partisani M, Priester M, Rey D, Majerholc C, Zucman D, Assi A, Lafeuillade A, de Jaureguiberry JP, Gisserot O, Aquilina C, du Clary FP, Alvarez M, Chauveau M, Delobel P, Garipuy D, Labau E, Marchou B, Massip P, Mularczyk M, Obadia M, Ajana F, Allienne C, Baclet V, de la Tribonnière X, Huleux T, Melliez H, Meybeck A, Riff B, Valette M, Viget N, Bastides F, Bernard L, Gras G, Guadagnin P, May T, Rabaud C, Dos Santos A, Poinsignon Y, Derradji O, Escaut L, Teicher E, Vittecoq D, Bantsima J, Caraux-Paz P, Patey O., Lissalde, Claire, and 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)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Social Psychology, Social stigma, Cross-sectional study, Social Stigma, Stigma (botany), HIV Infections, 03 medical and health sciences, Discrimination, Psychological, 0302 clinical medicine, Criminalization, 5. Gender equality, Criminal Law, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Psychiatry, Prejudice (legal term), Transients and Migrants, Depressive Disorder, Major, Stereotyping, 030505 public health, Public health, Public Health, Environmental and Occupational Health, HIV, Awareness, Middle Aged, 16. Peace & justice, Health psychology, Cross-Sectional Studies, Sexual Partners, Infectious Diseases, Attitude, Socioeconomic Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Criminal law, Female, Key population, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, 0305 other medical science, Psychology, Prejudice
Abstract

International audience; Some of the 12 criminal trials and sentences in France for HIV transmission in 1998-2011 attracted substantial public attention , with a possible negative impact on people living with HIV (PLWH) through reinforced stigma and discrimination. This analysis aimed to characterize PLWH enrolled in the representative ANRS-VESPA2 survey, aware of and concerned about convictions for HIV transmission. Being a migrant from Sub-Saharan Africa, having difficult socioeconomic conditions, having unprotected sex with one's main partner and concealing one's HIV status were all factors statistically associated with concern about the sentences. Participants tempted to press charges against someone for infecting them were more likely to be younger, women, not living in a couple, unemployed, and to report a major depressive disorder. Concern about HIV-related criminal proceedings among the most vulnerable PLWH do not reflect the actual risk of prosecution they are exposed to. Resumen En Francia, algunos de los 12 juicios y sentencias relacionados con la contaminación del VIH en 1998-2011 suscitaron con-siderablemente el interés público. Esto pudo impactar negativamente las personas viviendo con VIH (PVVIH) aumentando su estigmatización y discriminación. Este análisis busca caracterizar las PVVIH, de la encuesta ANRS-VESPA2, informadas acerca de esos juicios e inquietos por la posibilidad de implicación en uno de ellos. Ser inmigrante subsahariano, las con-diciones socio-económicas desfavorables, las relaciones sexuales no protegidas con la pareja principal, y ocultar el VIH, están asociados a la posibilidad de ser implicados en un juicio. Por otro lado, aquellos que han intentado presentar cargos por contaminación del VIH fueron mayoritariamente jóvenes, mujeres, personas viviendo solas, desempleados, y personas en depresión. Los juicios por contaminación del VIH entre las PVVIH más vulnerables no reflejan el riesgo de acusación al que están expuestos.

Published
2018
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29. SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends

Author

Guido Kroemer, Audrey Paoletti, Awatef Allouch, Gabrielle Lê-Bury, Marie-Lise Gougeon, Cristina Di Primio, Annie David, Mauro Piacentini, Gianfranco Pancino, Guillaume Montagnac, Valentina Quercioli, Jean-Luc Perfettini, Asier Sáez-Cirión, Anna Cereseto, Roberta Nardacci, Frédéric Subra, David M. Ojcius, Florence Niedergang, Héla Saïdi, Saez-Cirion, Asier, Instituts Hospitalo-Universitaires B - Institut de Médecine Personnalisée du Cancer - - MMO (IHU-CANCER)2010 - ANR-10-IBHU-0001 - IBHU - VALID, Institut Gustave Roussy (IGR), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Saclay, Scuola Normale Superiore di Pisa (SNS), 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), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), National Institute for Infectious Diseases 'Lazzaro Spallanzani', HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Immunité Antivirale, Biothérapie et Vaccins, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], Arthur A. Dugoni School of Dentistry [San Francisco], University of the Pacific [San Francisco], University of the Pacific-University of the Pacific, Université Paris Diderot - Paris 7 (UPD7), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Università degli Studi di Roma Tor Vergata [Roma], Université Paris Descartes - Paris 5 (UPD5), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Métabolisme, cancer et immunité = Metabolism, Cancer & Immunity [CRC] (Equipe labellisée Ligue contre le cancer), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Pôle de biologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Department of Women's and Children's Health, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], This work was supported by funds from Agence Nationale de la Recherche (ANR-10-IBHU-0001, ANR-10-LABX33, and ANR-11-IDEX-003-01), Cancéropole Ile de France, Electricité de France, Fondation Gustave Roussy, Institut National du Cancer (INCA 9414), NATIXIS, SIDACTION, and the French National Agency for Research on AIDS and viral Hepatitis (ANRSH) (to J-LP and FN)., We acknowledge Dr Alessandro Donado, Yann Lecluse, Floriane Herit, and Pierre Bourdoncle (IMAG’IC facility of Institut Cochin) for their technical support, and Pr. Eric Solary for the pRLL-EF1-PGK-GFP lentiviral vector plasmid., ANR-10-IBHU-0001,MMO (IHU-CANCER),Institut de Médecine Personnalisée du Cancer(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), HIV, Inflammation et persistance, Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)

Subjects
0301 basic medicine, Permissiveness, Cell, Mutant, Drug Resistance, Cell Cycle Proteins, HIV Infections, Virus Replication, Microtubules, Medical and Health Sciences, 0302 clinical medicine, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Viral, Aetiology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Acetylation, Biological Sciences, Active Transport, 3. Good health, medicine.anatomical_structure, Infectious Diseases, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV/AIDS, Infectious diseases, Infection, Microtubule-Associated Proteins, medicine.drug, Biochemistry & Molecular Biology, Immunopathogenesis, Anti-HIV Agents, Active Transport, Cell Nucleus, Biology, Article, Virus, microtubules, 03 medical and health sciences, Microtubule, Raltegravir Potassium, Drug Resistance, Viral, medicine, Genetics, Humans, Permissive, Molecular Biology, Cell Nucleus, Cell Biology, Raltegravir, Virology, nuclear import, 030104 developmental biology, HIV-1, SUGT1
Abstract

International audience; Understanding the viral-host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.

Published
2020
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30. Sleep disturbances in HIV-HCV coinfected patients: indications for clinical management in the HCV cure era (ANRS CO13 HEPAVIH cohort)

Author

Dominique Salmon-Ceron, Maria Patrizia Carrieri, Fabienne Marcellin, Linda Wittkop, Marie Costa, Philippe Sogni, Issifou Yaya, Denis Lacoste, Hugues Aumaitre, Jessica Krause, Virginie Villes, Teresa Rojas Rojas, Camelia Protopopescu, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Coordination Régionale de la lutte contre l'infection à VIH (COREVIH Aquitaine), CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin-Hôpital du Tondu, Service des maladies infectieuses [CH Perpignan], Centre Hospitalier Saint Jean de Perpignan, Team MORPH3EUS (INSERM U1219 - UB - ISPED), 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)-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 d’information Médicale [CHU de Bordeaux] (Pôle de Santé Publique), 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), Université Paris Descartes - Paris 5 (UPD5), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du système immunitaire (Inserm U1223), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], 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), This work was supported by the French National Agency for Research on Aids and Viral Hepatitis (ANRS: France Recherche Nord & sud Sida-hiv Hépatites), with the participation of Abbott France, Glaxo-Smith-Kline, Roche, Schering-Plough, BMS, Merck-Serono., ANRS CO13 HEPAVIH Study Group : Scientific Committee of the ANRS CO13 HEPAVIH Study Group: D. Salmon (co-Principal investigator), L. Wittkop (co- Principal Investigator), P. Sogni (co-Principal Investigator), L. Esterle (project manager), P. Trimoulet, J. Izopet, L. Serfaty, V. Paradis, B. Spire, P. Carrieri, M.A. Valantin, G. Pialoux, J. Chas, I. Poizot-Martin, K. Barange, A. Naqvi, E. Rosenthal, A. Bicart-See, O. Bouchaud, A. Gervais, C. Lascoux-Combe, C. Goujard, K. Lacombe, C. Duvivier, D. Vittecoq, D. Neau, P. Morlat, F. Bani-Sadr, L. Meyer, F. Boufassa, B. Autran, A.M. Roque, C. Solas, H. Fontaine, D. Costagliola, L. Piroth, A. Simon, D. Zucman, F. Boué, P. Miailhes, E. Billaud, H. Aumaître, D. Rey, G. Peytavin, V. Petrov-Sanchez, A. Pailhé. Clinical Centres (ward/participating physicians): APHP Cochin, Paris (Médecine Interne et Maladies Infectieuses: D. Salmon, R. Usubillaga, Hépato-gastro-entérologie: P. Sogni, Anatomo-pathologie: B. Terris, Virologie: P. Tremeaux), APHP Pitié-Salpétrière, Paris (Maladies Infectieuses et Tropicales: C. Katlama, M.A. Valantin, H. Stitou, Hépato-gastro-entérologie: Y. Benhamou, Anatomo-pathologie: F. Charlotte, Virologie: S. Fourati), APHP Pitié-Salpétrière, Paris (Médecine Interne: A. Simon, P. Cacoub, S. Nafissa), APHM Sainte- Marguerite, Marseille (Service d’Immuno-Hématologie Clinique: I. Poizot-Martin, O. Zaegel, H. Laroche, Virologie: C. Tamalet), APHP Tenon, Paris (Maladies Infectieuses et Tropicales: G. Pialoux, J. Chas, Anatomo-pathologie: P. Callard, F. Bendjaballah, Virologie: C. Le Pendeven), CHU Purpan, Toulouse (Maladies Infectieuses et Tropicales: B. Marchou, Hépato-gastro-entérologie: L. Alric, K. Barange, S. Metivier, Anatomo-pathologie: J. Selves, Virologie: F. Larroquette), CHU Archet, Nice (Médecine Interne: E. Rosenthal, Infectiologie: A. Naqvi, V. Rio, Anatomo-pathologie: J. Haudebourg, M.C. Saint-Paul, Virologie: C. Partouche), APHP Avicenne, Bobigny (Médecine Interne – Unité VIH: O. Bouchaud, Anatomo-pathologie: M. Ziol, Virologie: Y. Baazia), Hôpital Joseph Ducuing, Toulouse (Médecine Interne: M. Uzan, A. Bicart-See, D. Garipuy, M.J. Ferro-Collados, Virologie: F. Nicot), APHP Bichat-Claude Bernard, Paris (Maladies Infectieuses:, A. Gervais, Y. Yazdanpanah, Anatomo-pathologie: H. Adle- Biassette, Virologie: G. Alexandre), APHP Saint-Louis, Paris (Maladies infectieuses: C. Lascoux-Combe, J.M. Molina, Anatomo-pathologie: P. Bertheau, Virologie: M.L. Chaix, C. Delaugerre, S. Maylin), APHP Saint-Antoine (Maladies Infectieuses et Tropicales:, K. Lacombe, J. Bottero, J. Krause P.M. Girard, Anatomo-pathologie: D. Wendum, P. Cervera, J. Adam, Virologie: C. Viala), APHP Bicêtre, Paris (Médecine Interne: C. Goujard, Y. Quertainmont, E. Teicher, Virologie: C. Pallier, Maladies Infectieuses: D. Vittecoq), APHP Necker, Paris (Maladies Infectieuses et Tropicales: O. Lortholary, C. Duvivier, C. Rouzaud, J. Lourenco, F. Touam, C. Louisin: Virologie: V. Avettand-Fenoel, A. Mélard), CHU Pellegrin, Bordeaux (Maladies Infectieuses et Tropicales: D. Neau, A. Ochoa, E. Blanchard, S. Castet-Lafarie, C. Cazanave, D. Malvy, M. Dupon, H. Dutronc, F. Dauchy, L. Lacaze-Buzy, Anatomopathologie: P. Bioulac-Sage, Virologie: P. Trimoulet, S. Reigadas), Hôpital Saint-André, Bordeaux (Médecine Interne et Maladies Infectieuses: Médecine Interne et Maladies Infectieuses: P. Morlat, D. Lacoste, F. Bonnet, N. Bernard, M. Hessamfar, J.F. Paccalin, C. Martell, M.C. Pertusa, M. Vandenhende, P. Merciéer, D. Malvy, T. Pistone, M.C. Receveur, M. Méchain, P. Duffau, C Rivoisy, I. Faure, S. Caldato, Anatomo-pathologie: P. Bioulac-Sage, Hôpital du Haut-Levêque, Bordeaux (Médecine Interne: J.L. Pellegrin, J.F. Viallard, E. Lazzaro, C. Greib, Hôpital FOCH, Suresnes (Médecine Interne: D. Zucman, C. Majerholc, Virologie: E. Farfour), APHP Antoine Béclère, Clamart (Médecine Interne: F. Boué, J. Polo Devoto, I. Kansau, V. Chambrin, C. Pignon, L. Berroukeche, R. Fior, V. Martinez, Virologie: C. Deback), CHU Henri Mondor, Créteil (Immunologie Clinique: Y. Lévy, S. Dominguez, J.D. Lelièvre, A.S. Lascaux, G. Melica), CHU Hôtel Dieu, Nantes (Maladies Infectieuses et Tropicales: E. Billaud, F. Raffi, C. Allavena , V. Reliquet, D. Boutoille, C. Biron, Virologie: A. Rodallec, L. Le Guen), Hôpital de la Croix Rousse, Lyon (Maladies Infectieuses et Tropicales: P. Miailhes, D. Peyramond, C. Chidiac, F. Ader, F. Biron, A. Boibieux, L. Cotte, T. Ferry, T. Perpoint, J. Koffi, F. Zoulim, F. Bailly, P. Lack, M. Maynard, S. Radenne, M. Amiri, Virologie: C. Scholtes, T.T. Le-Thi), CHU Dijon, Dijon (Département d’infectiologie: L. Piroth, P. Chavanet M. Duong Van Huyen, M. Buisson, A. Waldner-Combernoux, S. Mahy, R. Binois, A.L. Simonet-Lann, D. Croisier-Bertin), CH Perpignan, Perpignan (Maladies infectieuses et tropicales: H. Aumaître), CHU Robert Debré, Reims (Médecine interne, maladies infectieuses et immunologie clinique: F. Bani-Sadr, D. Lambert, Y. Nguyen, J.L. Berger), CHRU Strasbourg (Le Trait d’Union: D. Rey, M. Partisani, M.L. Batard, C. Cheneau, M. Priester, C. Bernard- Henry, E. de Mautort, Virologie: P. Gantner et S. Fafi-Kremer), APHP Bichat-Claude Bernard (Pharmacologie: G. Peytavin). Data collection: F. Roustant, I. Kmiec, L. Traore, S. Lepuil, S. Parlier, V. Sicart-Payssan, E. Bedel, F. Touam, C. Louisin, M. Mole, C. Bolliot, M. Mebarki, A. Adda-Lievin, F.Z. Makhoukhi, O. Braik, R. Bayoud, M.P. Pietri, V. Le Baut, D. Bornarel, C. Chesnel, D. Beniken, M. Pauchard, S. Akel, S. Caldato, C. Lions, L. Chalal, Z. Julia, H. Hue, A. Soria, M. Cavellec, S. Breau, A. Joulie, P. Fisher, C. Ondo Eyene, S. Ogoudjobi, C. Brochier, V. Thoirain-Galvan. Management, statistical analyses: E. Boerg, P. Carrieri, V. Conte, L. Dequae- Merchadou,M.Desvallees, N. Douiri, L. Esterle, C. Gilbert, S. Gillet, R. Knight, F. Marcellin, L. Michel, M. Mora, C. Protopopescu, P. Roux, B. Spire, S. Tezkratt, I. Yaya, T. Barré, T. Rojas, V. Villes, M. Baudoin, M. Santos., Dupuis, Christine, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Sleep Wake Disorders, medicine.medical_specialty, Longitudinal study, Time Factors, Hepatitis C virus, Population, Human immunodeficiency virus (HIV), HIV Infections, Hepacivirus, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Medicine, Humans, 030212 general & internal medicine, education, Retrospective Studies, education.field_of_study, Hepatology, Cognitive Behavioral Therapy, business.industry, Gastroenterology, virus diseases, HIV, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, Middle Aged, Sleep in non-human animals, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Quality of Life, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

International audience; OBJECTIVES:Although common among patients coinfected with HIV and hepatitis C virus (HCV), sleep disturbances (SD) are still poorly documented in this population in the HCV cure era. This longitudinal study aimed at analysing SD in HIV-HCV coinfected patients and identifying their clinical and sociobehavioural correlates.METHODS:We used 5-year annual follow-up data from 1047 participants in the French National Agency for Research on Aids and Viral Hepatitis Cohort 13 'Hépatite et VIH' (ANRS CO13 HEPAVIH) cohort of HIV-HCV coinfected patients to identify clinical (medical records) and behavioural (self-administered questionnaires) correlates of SD (mixed-effects logistic regression). SD were identified using one item documenting the occurrence of insomnia or difficulty falling asleep (ANRS 'Action Coordonnée 24' self-reported symptoms checklist), and two items documenting perceived sleep quality (Center for Epidemiologic Studies Depression and WHO Quality of Life HIV-specific brief scales).RESULTS:Seven hundred and sixteen (68.4%) patients with completed self-administered questionnaires reported SD at their most recent follow-up visit. In the multivariable model, hazardous alcohol consumption (Alcohol Use Disorders Identification Test-Consumption score≥4 for men, ≥3 for women) (adjusted odds ratio=1.61; 95% confidence interval: 1.09-2.36), depressive symptoms (6.78; 4.36-10.55) and the number of other physical and psychological self-reported symptoms (1.10; 1.07-1.13) were associated independently with SD after adjustment for sex, age and employment status. HCV cure was not associated significantly with SD.CONCLUSION:SD remain frequent in HIV-HCV coinfected patients and are associated with a series of modifiable behavioural risk factors. Independent of HCV cure, improved screening and comprehensive management of alcohol use, physical and psychological self-reported symptoms and depression are essential in this population. Closer investigation of these risk factors of SDs may both increase sleep quality and indirectly improve patients' clinical outcomes.

Published
2019
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31. Liver Enzyme Elevation in Pregnant Women Receiving Antiretroviral Therapy in the ANRS-French Perinatal Cohort

Author

Roland Tubiana, Françoise Meier, Albert Faye, Jérôme Le Chenadec, Laurent Mandelbrot, Josiane Warszawski, Stéphane Blanche, Jeanne Sibiude, 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), Département d'obstétrique et de gynécologie [AP-HP Hôpital Louis-Mourier] (DHU Risks in Pregnancy), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département d'infectiologie [AP-HP Hôpital Louis Mourier, Colombes], Hôpital Louis Mourier - AP-HP [Colombes], Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). ANRS is an autonomous agency at Inserm. The ANRS functions as promotor and funding and had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Jeanne Sibiude received a grant from ANRS [n°14055] and from AIDS Healthcare Foundation for this work., ANRS-French Perinatal Cohort Study Group, Comets, Emmanuelle, 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), and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]

Subjects
Adult, medicine.medical_specialty, Anti-HIV Agents, HIV Infections, 030312 virology, 03 medical and health sciences, Young Adult, Pregnancy, medicine, Humans, Pharmacology (medical), Aspartate Aminotransferases, Pregnancy Complications, Infectious, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Obstetrics, business.industry, Hazard ratio, Lopinavir, Alanine Transaminase, biochemical phenomena, metabolism, and nutrition, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Regimen, Infectious Diseases, Nelfinavir, Liver, Cohort, embryonic structures, Coinfection, Female, France, business, Cholestasis of pregnancy, medicine.drug
Abstract

International audience; BACKGROUND:High rates of liver enzyme elevation (LEE) in women receiving antiretroviral treatment (ART) during pregnancy have been reported but causes remain unclear. We estimated the prevalence and risk factors of LEE in a national prospective multicenter cohort.METHODS:We studied 5748 pregnant women living with HIV enrolled in the French Perinatal Cohort 2005-2014, treated with ART, with no active hepatitis B or C co-infection. Adjusted hazard ratio (aHR) were estimated using Cox models with ART as time-dependent variable, separately for women on ART at conception and those initiating ART during pregnancy.RESULTS:LEE (grade>1) was observed in 16.7%, grade 3-4 in 2%. Among women with LEE, 6.7% had preeclampsia, 9.8% intrahepatic cholestasis of pregnancy, and 1.4% other identified medical causes. Most LEE (82.2%) were unexplained. In women with unexplained LEE, LEE was the reason for hospitalization in 51 (6%) women, cesarean section in 13 (2%), induction of labour in 3 (0.4%), and change in ART regimen in 49 (6%) women. Unexplained LEE was associated with higher risk of preterm births, p

Published
2019
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32. Polyfunctional HIV-specific T cells in Post-Treatment Controllers

Author

Samri, Assia, Bacchus-Souffan, Charlin, Hocqueloux, Laurent, Avettand-Fenoel, Véronique, Descours, Benjamin, Theodorou, Ioannis, Larsen, Martin, Sáez-Cirión, Asier, Rouzioux, Christine, Autran, Brigitte, Group, Anrs Visconti, Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional d'Orléans (CHRO), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), The study was supported by the ANRS, the French National Agency for Research on AIDS, and Viral Hepatitis (Grant ANRS EP47). The promoter is the Centre Hospitalier Regional d’Orleans, Université Pierre et Marie Curie, Univ Paris 06 ( Sorbonne University ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Régional d'Orléans ( CHR ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], HIV, Inflammation et persistance, Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie [CHU Pitié-Salpétrière], 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 Régional d'Orléans (CHR), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, Anti-HIV Agents, Immunology, Human immunodeficiency virus (HIV), HIV Infections, CD8-Positive T-Lymphocytes, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Secondary Prevention, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Immunology and Allergy, Cytotoxic T cell, 030212 general & internal medicine, Secondary prevention, business.industry, virus diseases, 3. Good health, 030104 developmental biology, Infectious Diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Post treatment, business, After treatment
Abstract

International audience; To further understand the exceptional HIV-1 control observed in Post-Treatment Controllers (PTCs) from the Virological and Immunological Sustained CONtrol after Treatment Interruption study we investigated their HIV-specific T-cell responses. Polyfunctionality of HIV-specific CD4 and CD8 T cells and the ratios of HIV-specific CD4 T cells per infected cells were similar in post-treatment controllers, continuously early-treated patients and long-term non-progressors Overall early treatment appears to preserve robust HIV-specific CD4 T cells, which might contribute to the posttreatment control of HIV.

Published
2016
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33. Innate immune cell responses in non pathogenic versus pathogenic SIV infections

Author

Philippe Rascle, Nicolas Huot, Michaela Müller-Trutwin, Beatrice Jacquelin, Thalia Garcia-Tellez, Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), We would like to thank the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Vaccine Research Institute funded by the Investissements d’Avenir program’ managed by the ANR under reference ANR-10-LABX-77, as well as the Center for Infectious Disease models and Innovative Therapies (IDMIT) funded by 'Programme investissements d'avenir' under grant agreement N° ANR-11-INBS-0008)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), Vaccine Research Institute (VRI), HIV, Inflammation et persistance, and Institut Pasteur [Paris]

Subjects
0301 basic medicine, Cell type, Myeloid, Neutrophils, animal diseases, Neutrophile, Cell, Simian Acquired Immunodeficiency Syndrome, innate lymphoid cells, Inflammation, NK cells, Biology, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Animals, dendritic cells, Innate immune system, [SDV.BA]Life Sciences [q-bio]/Animal biology, Innate lymphoid cell, virus diseases, natural hosts, Macaca mulatta, Immunity, Innate, 3. Good health, Killer Cells, Natural, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, medicine.anatomical_structure, Host-Pathogen Interactions, Immunology, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, Simian Immunodeficiency Virus, medicine.symptom, neutrophiles, 030215 immunology
Abstract

International audience; HIV-1/SIVmac infections deeply disturb innate host responses. Most studies have focused on the impact on dendritic cells and NK cells. A few but insufficient data are available on other innate immune cell types, such as neutrophils. It has been shown that innate lymphoid cells are depleted early and irreversibly during SIVmac/HIV-1 infections. Studies in natural hosts of SIV have contributed to pinpoint that early control of inflammation is crucial. In natural hosts, plasmacytoid dendritic cells, myeloid dendritic cells and NK cells are depleted during acute infection but return to normal levels by the end of acute infection. We summarize here the similarities and differences of various types of innate immune responses in natural hosts compared to pathogenic HIV/SIV mac infections.

Published
2016
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34. HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry

Author

Haithem Dakhli, David M. Ojcius, Maxime Thoreau, Héla Saïdi, Eric Solary, Awatef Allouch, Jean-Luc Perfettini, Olivier Lambotte, Marina Caillet, Eric Deutsch, Olivier Delelis, Qiuji Wu, Zeinaf Muradova, Mauro Piacentini, Gianfranco Pancino, Roger Le Grand, Syed Qasim Raza, Audrey Paoletti, Asier Sáez-Cirión, Béatrice Poirier-Beaudouin, Nathalie Dereuddre-Bosquet, Frédéric Subra, Laurent Voisin, Guido Kroemer, Marie-Lise Gougeon, Roberta Nardacci, Frédéric Law, Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose, cancer et immunité (U848), Immunité Anti-virale, Biothérapie et Vaccins (IABV), Institut Pasteur [Paris] (IP), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), 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, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, University of the South Pacific (USP), Université Paris Diderot - Paris 7 (UPD7), Hématopoïèse normale et pathologique, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Università degli Studi di Roma Tor Vergata [Roma], Agence Nationale de la RechercheFrench National Research Agency (ANR) [ANR-10-IBHU-0001, ANR-10-LABX33, ANR-11-IDEX-003-01], Electricite de France, MIUR (FIRB)Ministero dell' Istruzione, dell' Universita e della Ricerca (MIUR), Ministry of Health of Italy 'Ricerca Finalizzata', ANR under the program 'Investissements d'Avenir'French National Research Agency (ANR) [ANR-10-LABX-33, ANR-11-IDEX-0003-01], Fondation Gustave Roussy, AIRCAssociazione Italiana per la Ricerca sul Cancro (AIRC), European Commission 'Transpath' Marie Curie Project, Agence Nationale de Recherche sur le Sida et sur les Hepatites (ANRSH)French National Research Agency (ANR), Higher Education Commission (Pakistan)Higher Education Commission of Pakistan, Laboratory of Excellence LERMIT, Institut National du CancerInstitut National du Cancer (INCA) France [INCA 9414], Canceropole Ile-de-FranceRegion Ile-de-France, Institut National du Cancer (INCa)Institut National du Cancer (INCA) France, NATIXIS, Sidaction, French National Agency for Research on AIDS and Viral Hepatitis (ANRSH)French National Research Agency (ANR), Ligue contre le Cancer (equipe labellisee), Agence National de la Recherche (ANR) -Projets blancsFrench National Research Agency (ANR), Institut Universitaire de France, Ministry of Health of Italy 'Ricerca Corrente', LabEx Immuno-Oncology, RHU Torino Lumiere, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC Cancer Research and Personalized Medicine (CARPEM), MIUR (PRIN 2012)Ministero dell' Istruzione, dell' Universita e della Ricerca (MIUR), We gratefully acknowledge Y. Lecluse and S. Salome-Desnoulez for technical support., ANR-10-IBHU-0001,MMO (IHU-CANCER),Institut de Médecine Personnalisée du Cancer(2010), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 289964,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,TRANSPATH(2011), Leriche, Marianne, Instituts Hospitalo-Universitaires B - Institut de Médecine Personnalisée du Cancer - - MMO (IHU-CANCER)2010 - ANR-10-IBHU-0001 - IBHU - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Transglutaminase in disease: a novel therapeutic target? - TRANSPATH - - EC:FP7:PEOPLE2011-11-01 - 2015-10-31 - 289964 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut Pasteur [Paris], and HIV, Inflammation et persistance

Subjects
0301 basic medicine, CBL, Settore BIO/06, CXCR4, General Biochemistry, Genetics and Molecular Biology, HIV, NLRP3, P2Y2, inflammasome, viral entry, Polymerization, 03 medical and health sciences, 0302 clinical medicine, Viral entry, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Humans, [INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL], Receptor, lcsh:QH301-705.5, Actin, biology, integumentary system, Chemistry, Purinergic receptor, Inflammasome, Virus Internalization, Actins, 3. Good health, Cell biology, Ubiquitin ligase, 030104 developmental biology, lcsh:Biology (General), biology.protein, HIV-1, Phosphorylation, [INFO.INFO-DL] Computer Science [cs]/Digital Libraries [cs.DL], 030217 neurology & neurosurgery, medicine.drug, Signal Transduction
Abstract

Summary: Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402∗) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry. : Paoletti et al. identified a constitutive interaction between NLRP3 and P2Y2 that regulates HIV-1 entry into target cells. They revealed that NLRP3 represses viral entry by impairing F-actin reorganization. HIV-1 overcomes this host cellular resistance by inducing NLRP3 degradation through the activation of P2Y2-dependent signaling pathway. Keywords: NLRP3, P2Y2, CBL, inflammasome, viral entry, HIV

Published
2019
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35. Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infection

Author

Christine Rouzioux, Asma Essat, Véronique Avettand-Fenoel, Adeline Melard, Olivier Delelis, Tiphaine Lenfant, Marc Bary, Marine Gousset, Jean-Paul Viard, Laurence Meyer, Faroudy Boufassa, Cécile Goujard, Pauline Trémeaux, CCSD, Accord Elsevier, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), 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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], 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), The ANRS-PRIMO and SEROCO cohorts are sponsored by the ANRS (French National Agency for Research on AIDS and Viral Hepatitis). This work was funded by the ANRS., ANRS-SEROCO and PRIMO cohorts, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, 0301 basic medicine, Research paper, Human immunodeficiency virus (HIV), Natural history, HIV Infections, Context (language use), medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Integrated HIV DNA, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), medicine, Humans, Primary HIV infection, Seroconversion, Proportional Hazards Models, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, General Medicine, Middle Aged, medicine.disease, Virology, 3. Good health, Acquired immunodeficiency syndrome, Kinetics, 030104 developmental biology, Anti-Retroviral Agents, Reservoirs, 030220 oncology & carcinogenesis, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Leukocytes, Mononuclear, RNA, Viral, Female, business, Viral hepatitis, Total HIV DNA, Hiv disease
Abstract

International audience; BACKGROUND:In the current context of research on HIV reservoirs, offering new insights into the persistence of HIV DNA in infected cells, which prevents viral eradication, may aid in identifying cure strategies. This study aimed to describe the establishment of stable integrated forms among total HIV DNA during primary infection (PHI) and their dynamics during the natural history of infection.METHODS:Total and integrated HIV DNA were quantified in blood from 74 PHI patients and 97 recent seroconverters (

Published
2019
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36. Intimate partner violence against HIV-positive Cameroonian women: Prevalence, associated factors and relationship with antiretroviral therapy discontinuity-results from the ANRS-12288 EVOLCam survey

Author

Khadim Ndiaye, Laura March, Christopher Kuaban, Luis Sagaon-Teyssier, Marie-Thérèse Mengue, Marie Suzan-Monti, Christian Laurent, Sylvie Boyer, Bruno Spire, Marion Fiorentino, Laurent Vidal, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Université Catholique d'Afrique Centrale - Institut Catholique de Yaoundé (UCAC), 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), Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM), This study was funded by the French National Agency for Research on AIDS and viral hepatitis (ANRS)., Aiello, Mélisande, 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), Université catholique d'Afrique centrale, Institut catholique de Yaoundé, Université de Yaoundé I [Yaoundé], Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI)

Subjects
Sexual partner, Adult, intimate partner violence, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), Stigma (botany), lcsh:Medicine, HIV Infections, 030312 virology, medicine.disease_cause, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, 5. Gender equality, Prevalence, Medicine, Humans, 030212 general & internal medicine, Cameroon, Hiv treatment, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, business.industry, lcsh:R, Central africa, HIV, General Medicine, Odds ratio, Middle Aged, Antiretroviral therapy, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Anti-Retroviral Agents, Socioeconomic Factors, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Domestic violence, Women's Health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, women, business, antiretroviral therapy interruption, Primary, Demography
Abstract

Background: Intimate partner violence in its various forms increases HIV exposure in female victims and potentially jeopardizes the HIV treatment cascade, for instance, by impeding engagement in and adherence to care. Elevated rates of HIV and intimate partner violence are reported in Central Africa. Evidence on the effect of intimate partner violence on antiviral therapy interruption is lacking in Cameroon, where only 330,000 women live with HIV and only 19% of HIV-positive people are virally suppressed. This study aimed to assess the prevalence and factors of intimate partner violence against HIV-positive women and its relationship with antiretroviral therapy interruption ⩾1 month. Methods: The EVOLCam cross-sectional survey was conducted in 19 hospitals in the Center and Littoral regions. The study sample comprised antiviral therapy–treated women declaring at least one sexual partner in the previous year. Scores of recent emotional, physical, extreme physical and sexual intimate partner violence were built using principal component analysis and categorized under no, occasional or frequent intimate partner violence. Multivariate logistic analyses were performed to investigate the relationship between intimate partner violence and recent antiretroviral therapy interruption ⩾1 month, and associated factors. Results: Among the 894 analyzed women, the prevalence of intimate partner violence was 29% (emotional), 22% (physical), 13% (extreme physical) and 18% (sexual). Frequent physical intimate partner violence was a significant risk factor of antiretroviral therapy interruption ⩾1 month (adjusted odds ratio = 2.42 (95% confidence interval = 1.00; 5.87)). It was also associated with HIV-related stigma (2.53 (1.58; 4.02)), living with a main partner (2.03 (1.20; 3.44) and non-defensive violence against this partner (5.75 (3.53; 9.36)). Conclusion: Intimate partner violence is a potential barrier to antiviral therapy continuity and aggravates vulnerability of Cameroonian HIV-positive women. The prevention and detection of intimate partner violence by HIV services might help to reach the last “90” of the 90-90-90 targets.

Published
2019
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37. Dehydrojuncusol, a Natural Phenanthrene Compound Extracted from Juncus maritimus Is a New Inhibitor of Hepatitis C Virus RNA Replication

Author

Arielle R. Rosenberg, Alexandre Vandeputte, Karin Seron, Yves Rouillé, Muriel Lavie, Priscille Brodin, Jean Dubuisson, Sevser Sahpaz, Véronique Pène, Riadh Ksouri, Céline Rivière, Ramla Sahli, Marie-Emmanuelle Sahuc, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Viollette (ICV) - EA 7394 (ICV), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de la Recherche Agronomique (INRA)-Université d'Artois (UA)-Institut Supérieur d'Agriculture, Laboratoire des plantes aromatiques et médicinales (Faculté des Sciences Mathématiques, Physiques et Naturelles, Tunis) (LPAM), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM)-Université de Tunis El Manar (UTM), Virologie de l'hépatite C (EA 4474), Université Paris Descartes - Paris 5 (UPD5), This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS-18208), the European Community (ERC-STG INTRACELLTB grant 260901), the Agence Nationale de la Recherche (ANR-10-EQPX-04-01), the Fonds Européen de Développement Régional (Feder) (12001407 [D-AL] EquipEx ImagInEx BioMed), and the Région Nord-Pas-de-Calais (convention 12000080), We thank platforms of CUMA (University of Lille 2, J. F. Goossens) and LARMN (University of Lille 2, N. Azaroual) for access to equipment. We are grateful to J. Bukh, C. M. Rice, and T. Wakita for providing essential reagents. We are also grateful to Abderrazak Smaoui (Biotechnology Centre of Borj-Cédria) concerning botanical identification and to Thibaut Vausselin for useful discussions. M.-E.S. is a recipient of a Ph.D. Fellowship provided by the French Government., European Project: 260901,EC:FP7:ERC,ERC-2010-StG_20091118,INTRACELLTB(2010), Université d'Artois (UA)-Institut National de la Recherche Agronomique (INRA)-Université du Littoral Côte d'Opale (ULCO)-Institut Supérieur d'Agriculture-Université de Lille, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis - Faculty of Mathematical, Physical and Natural Sciences of Tunis, Séron, Karin, and A Chemical Genomics Approach of Intracellular Mycobacterium tuberculosis Towards Defining Specific Host Pathogen Interactions - INTRACELLTB - - EC:FP7:ERC2010-12-01 - 2015-11-30 - 260901 - VALID

Subjects
hepatitis C virus, phenanthrene, dehydrojuncusol, Sofosbuvir, Hepatitis C virus, [SDV]Life Sciences [q-bio], Immunology, Context (language use), Biology, medicine.disease_cause, Microbiology, natural antimicrobial products, 03 medical and health sciences, 0302 clinical medicine, Virology, Genotype, antiviral agents, medicine, Replicon, NS5A, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, virus diseases, Hepatitis C, medicine.disease, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Viral replication, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, viral replication, 030211 gastroenterology & hepatology, medicine.drug
Abstract

International audience; Recent emergence of direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) proteins has considerably enhanced the success of antiviral therapy. However, the appearance of DAA-resistant-associated variants is a cause of treatment failure, and the high cost of DAAs renders the therapy not accessible in countries with inadequate medical infrastructures. Therefore, the search for new inhibitors with a lower cost of production should be pursued. In this context, the crude extract of Juncus maritimus Lam. was shown to exhibit high antiviral activity against HCV in cell culture. Bio-guided fractionation allowed the isolation and identification of the active compound, dehydrojuncusol. A time-of-addition assay showed that dehydrojuncusol significantly inhibited HCV infection when added after virus inoculation of HCV genotype 2a (50% effective concentration [EC50] = 1.35 µM). This antiviral activity was confirmed with an HCV subgenomic replicon, and no effect on HCV pseudoparticle entry was observed. Antiviral activity of dehydrojuncusol was also demonstrated in primary human hepatocytes. No in vitro toxicity was observed at active concentrations. Dehydrojuncusol is also efficient on HCV genotype 3a and can be used in combination with sofosbuvir. Interestingly, dehydrojuncusol was able to inhibit RNA replication of two frequent daclatasvir-resistant mutants (L31M or Y93H in NS5A). Finally, mutants resistant to dehydrojuncusol were obtained and showed that the HCV NS5A protein is the target of the molecule. In conclusion, dehydrojuncusol, a natural compound extracted from J. maritimus, inhibits infection of different HCV genotypes by targeting the NS5A protein and is active against resistant HCV variants frequently found in patients with treatment failure.IMPORTANCE Tens of millions of people are infected with hepatitis C virus (HCV) worldwide. Recently marketed direct-acting antivirals (DAAs) targeting HCV proteins have enhanced the efficacy of treatment. However, due to its high cost, this new therapy is not accessible to the vast majority of infected patients. Furthermore, treatment failures have also been reported due to the appearance of viral resistance. Here, we report on the identification of a new HCV inhibitor, dehydrojuncusol, that targets HCV NS5A and is able to inhibit RNA replication of replicons harboring resistance mutations to anti-NS5A DAAs used in current therapy. Dehydrojuncusol is a natural compound isolated from Juncus maritimus, a halophilic plant species that is very common in coastlines worldwide. This molecule might serve as a lead for the development of a new therapy that is more accessible to hepatitis C patients in the future

Published
2019
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38. Profil, pratiques à risques et besoins des personnes qui injectent du sulfate de morphine : Résultats de l'étude ANRS-AERLI

Author

Roux, Perrine, Mezaache, Salim, Briand-Madrid, Laélia, Debrus, Marie, Khatmi, Nicolas, Maradan, Gwenaelle, Protopopescu, Camelia, Rojas-Castro, Daniela, Carrieri, Patrizia, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Pantin, France], Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Médecins du Monde [Paris, France] (Association médicale militante de solidarité internationale), and This study received external funding from the French National Agency for Research for AIDS and Viral Hepatitis (ANRS).

Subjects
Drug injection, Risk practices, Community-based research, Morphine sulfate, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Educational intervention, digestive system diseases
Abstract

International audience; AIMS:In France, a non-negligible proportion of opioid-dependent individuals inject morphine sulfate. Although it has not yet been officially approved as an opioid substitution treatment (OST), some physicians can prescribe its use for people in methadone or buprenorphine treatment failure. Longitudinal data from the ANRS-AERLI study, which evaluated an educational intervention for safer injection called AERLI, provided us the opportunity to better characterize the profile, risk practices and needs of people who inject morphine sulfate (MSI), through comparison with other injectors, and to identify correlates of HIV/HCV risk practices in this group.METHODS:The national multisite ANRS-AERLI study assessed the impact of AERLI offered in volunteer harm reduction (HR) centers ("with intervention") (n = 113) through comparison with standard HR centers ("without intervention") (n = 127). All participants were scheduled to be followed up for 12 months and have 3 telephone interviews: at baseline, 6 months and 12 months. We compared MSI (n = 79) with other opioid injectors (n = 161) and then used a mixed logistic model to identify factors associated with HIV/HCV risk practices among MSI.FINDINGS:Of the 240 eligible participants, 79 were regular MSI. They were less likely to use cocaine, crack or buprenorphine and to receive OST than other participants. Conversely, MSI were more likely to inject drugs more than three times a day and to report HIV/HCV risk practices. Among MSI, multivariate analysis showed that those receiving morphine sulfate as an OST were less likely to report such practices than other participants (aOR [95%CI] = 0.11 [0.02-0.61]).CONCLUSION:Our results show that while MSI use fewer stimulants, they have more HIV/HCV risk practices than other injectors. However, when MSI are prescribed morphine sulfate as a treatment, these practices tend to decrease. Our findings suggest the importance of increasing access to morphine sulfate as a new OST in France.

Published
2018
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39. A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

Author

Warren J. Leonard, Nima Rezaei, Kathryn Payne, Isabelle Meyts, Laurent Abel, Cindy S. Ma, Marianne Leruez-Ville, Janet Chou, Alain Hovnanian, Jian-Xin Lin, Simon J. Pelham, Danielle T. Avery, Matthieu Bouaziz, Bethany Pillay, Tanwir Habib, Anne Puel, Sevgi Keles, Juan Li, Isabelle Pellier, Jamel El-Benna, Bernhard Fleckenstein, Ahmet Ozen, Vivien Béziat, Ingrid Müller-Fleckenstein, Damien Chaussabel, Samaneh Zoghi, Yi Wang, Paul Gray, Matthias Titeux, Yoann Zerbib, Talal A. Chatila, Marie-Alexandra Alyanakian, Capucine Picard, Orli Wargon, Ayper Somer, Marie-Olivia Chandesris, Thibaut Leclercq, Ibtihal Benhsaien, Aziz Belkadi, Jean-Laurent Casanova, Romain Lévy, Peng Li, Geetha Rao, Ai Ing Lim, James P. Di Santo, Nico Marr, Sylvie Fraitag, Frédégonde About, Elissa K. Deenick, Bertrand Boisson, Jacinta Bustamante, Mélanie Migaud, Bodo Grimbacher, Aziz Bousfiha, Fatima Ailal, Safa Baris, Antoine Guérin, Stuart G. Tangye, Romain Guery, Ning Du, Vimel Rattina, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rockefeller University [New York], National Institutes of Health [Bethesda] (NIH), Garvan Institute of Medical Research [Darlinghurst, Australia], University of New South Wales [Sydney] (UNSW), CHU Ibn Rochd [Casablanca], Université Hassan II [Casablanca] (UH2MC), Service d'Immuno-Hémato-Oncologie Pédiatrique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, Universal Scientific Education and Research Network (USERN), Marmara University [Kadıköy - İstanbul], Necmettin Erbakan University [Konya, Turquie], Immunité Innée, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Harvard Medical School [Boston] (HMS), Boston Children's Hospital, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Sidra Medicine, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Freiburg University Medical Center, Sydney children's hospital, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Genetic skin diseases : from disease mechanism to therapies (Equipe Inserm U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [CHU Necker], Service d'immuno-hématologie pédiatrique [CHU Necker], Laboratoire de Virologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5), Centre d'étude des Déficits Immunitaires, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Istanbul University, Research Center for Immunodeficiencies [Tehran, Iran], Tehran University of Medical Sciences (TUMS), University of New South Wales [Canberra Campus] (UNSW), Howard Hughes Medical Institute [New York], New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), This work was supported by grants from INSERM, Paris Descartes University, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID), the Jeffrey Modell Foundation Translational Research Program, the French National Research Agency (ANR, grant nos. GENCMCD-ANR-11-BSV3–005-01, HGDIFD-ANR-14-CE15-0006-01, NKIR-ANR-13-PDOC-0025-01, and EURO-CMC-ANR-14-RARE-0005-02), and grants awarded under the 'Investissement d’avenir' program (grant no. ANR-10-IAHU-01), the National Institute of Allergy and Infectious Diseases of the NIH (grant nos. U01AI109697 and R01AI127564), the Rockefeller University, the Howard Hughes Medical Institute, the St. Giles Foundation, the Institut Pasteur, and FP7, under grant agreements 305578 (PathCO) and 317057 (HOMIN). We thank the Centre de Recherche Translationnelle (Institut Pasteur) for technical assistance. V.B. is supported by the ANR (grant no. NKIR-ANR-13-PDOC-0025-01). R.L. is supported by the INSERM Ph.D. program (Poste d’Accueil INSERM), a Fulbright grant (Franco-American commission), and a Philippe Foundation scholarship. Y.Z. received the 'médaille d’or du Centre Hospitalier Universitaire d’Amiens.' Y.W. is supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS, grant no. 13318). F. About holds a fellowship from Fondation pour la Recherche Médicale (FRM, grant no. FDM20140630671). A.G. is supported by an IFNGPHOX grant (no. ANR13-ISV3-0001-01) from ANR. B.G. was funded by BMBF (German Federal Ministry of Education and Research) grants 01E01303 and 01ZX1306F. I.M. is supported by a klinische onderzoeks-en opleidingsraad (clinical research council) grant from UZ Leuven, a klinisch onderzoeksfonds (clinical research fund) grant from KU Leuven, and an International Mobility Grant from Fonds voor Wetenschappelijk Onderzoek (fund for scientific research) Vlaanderen. C.S.M., E.K.D., and S.G.T. are supported by grants and fellowships from the National Health and Medical Research Council of Australia. C.S.M., P.G., E.K.D., and S.G.T. are members of CIRCA (Clinical Immunogenomics Research Consortia Australia), which is funded by the Office of Health and Medical Research of the NSW Government, the Jeffrey Modell Foundation, and the John Cook Brown Foundation. A.I.L. is a scholar of the Pasteur-Paris University International Ph.D. program and is supported by a Ph.D. International Training Network grant from the European Union’s Seventh Framework Program under grant agreement no. 317057 (HOMIN). T.A.C. was supported by a grant from the National Institute of Allergy and Infectious Diseases of the NIH (5R01AI065617). S.K. was supported by a grant from the Scientific and Technological Research Council of Turkey (1059B191300622). J.-X.L., P.L., N.D., and W.J.L. were supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH. A.P. was supported by an AP-HP interface contract., We thank the patients and their families for participating in this study. We thank J. E. Darnell and C. Mertens for advice and for providing reagents. We thank the members of the laboratory, especially F. Jabot-Hanin and V. Pedergnana, for their valuable input on linkage analysis, L. Amar, Y. Nemirovskaya, D. Papandrea, E. Anderson, M. Woollett, C. Desvallées, C. Patissier, and M. Corrias for administrative assistance, E. Jouanguy and Y. Itan for helpful discussions, S. Boucherit for clinical data collection, S. Jacques and the Cochin genomics platform for microarray experiments, and N. Goudin and R. Desveaux of the Necker Institute Imaging Facility., Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Garvan Institute of medical research, Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sidra Medicine [Doha, Qatar], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Sydney Children's hospital, 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 Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Beziat, Vivien, Li, Juan, Lin, Jian-Xin, Ma, Cindy S., Li, Peng, Bousfiha, Aziz, Pellier, Isabelle, Zoghi, Samaneh, Baris, Safa, Keles, Sevgi, Gray, Paul, Du, Ning, Wang, Yi, Zerbib, Yoann, Levy, Romain, Leclercq, Thibaut, About, Fredegonde, Lim, Ai Ing, Rao, Geetha, Payne, Kathryn, Pelham, Simon J., Avery, Danielle T., Deenick, Elissa K., Pillay, Bethany, Chou, Janet, Guery, Romain, Belkadi, Aziz, Guerin, Antoine, Migaud, Melanie, Rattina, Vimel, Ailal, Fatima, Benhsaien, Ibtihal, Bouaziz, Matthieu, Habib, Tanwir, Chaussabel, Damien, Marr, Nico, El-Benna, Jamel, Grimbacher, Bodo, Wargon, Orli, Bustamante, Jacinta, Boisson, Bertrand, Mueller-Fleckenstein, Ingrid, Fleckenstein, Bernhard, Chandesris, Marie-Olivia, Titeux, Matthias, Fraitag, Sylvie, Alyanakian, Marie-Alexandra, Leruez-Ville, Marianne, Picard, Capucine, Meyts, Isabelle, Di Santo, James P., Hovnanian, Alain, Somer, Ayper, Ozen, Ahmet, Rezaei, Nima, Chatila, Talal A., Abel, Laurent, Leonard, Warren J., Tangye, Stuart G., Puel, Anne, and Casanova, Jean-Laurent

Subjects
0301 basic medicine, INBORN-ERRORS, Immunoglobulin E, MESH: STAT3 Transcription Factor/immunology, Loss of heterozygosity, PRECISION MEDICINE, Transcription (biology), OF-FUNCTION MUTATIONS, STAT3, MESH: Transcription Factors/metabolism, CELL-DIFFERENTIATION, MESH: Th2 Cells/metabolism, MESH: Immunoglobulin E/immunology, MESH: Middle Aged, MESH: Gene Expression Regulation/immunology, Cell Differentiation, General Medicine, MESH: RNA, Messenger/metabolism, MESH: Immunoglobulin E/blood, MESH: Zinc Fingers/genetics, READ ALIGNMENT, MESH: Transcription, Genetic/immunology, MESH: Cell Nucleus/metabolism, MESH: Young Adult, [SDV.IMM]Life Sciences [q-bio]/Immunology, SIGNAL TRANSDUCER, Job Syndrome, MESH: Homozygote, STAT3 Transcription Factor, Cell type, MESH: Lymphocyte Count, MESH: Pedigree, MESH: STAT3 Transcription Factor/genetics, Immunology, Biology, Article, MESH: Job Syndrome/immunology, MESH: Genes, Recessive/genetics, DIFFERENTIAL EXPRESSION, MESH: Genes, Recessive/immunology, MESH: Job Syndrome/blood, MESH: Transcription Factors/genetics, 03 medical and health sciences, MESH: Whole Exome Sequencing, MESH: Exons/genetics, Humans, Transcription factor, Gene, MESH: Adolescent, MESH: Consanguinity, MESH: Humans, CLINICAL-FEATURES, MESH: Th17 Cells/metabolism, MESH: Th17 Cells/immunology, MESH: Cytokines/immunology, MESH: Adult, MESH: Loss of Function Mutation, MESH: Job Syndrome/genetics, MESH: Cell Differentiation/genetics, Molecular biology, MESH: Male, MESH: Th2 Cells/immunology, IL-21 RECEPTOR, 030104 developmental biology, Gene Expression Regulation, MESH: STAT3 Transcription Factor/metabolism, MESH: Promoter Regions, Genetic/genetics, MESH: Cell Differentiation/immunology, T-CELLS, STAT protein, biology.protein, Th17 Cells, MESH: Transcription Factors/immunology, MESH: Cytokines/metabolism, MESH: Female
Abstract

Comment in :Who regulates whom: ZNF341 is an additional player in the STAT3/TH17 song. [Sci Immunol. 2018]; International audience; Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.

Published
2018
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40. Impact of Alcohol and Coffee Intake on the Risk of Advanced Liver Fibrosis: A Longitudinal Analysis in HIV-HCV Coinfected Patients (ANRS CO-13 HEPAVIH Cohort)

Author

Yaya, Issifou, Marcellin, Fabienne, Costa, Marie, Morlat, Philippe, Protopopescu, Camelia, Pialoux, Gilles, Santos, Melina Erica, Wittkop, Linda, Esterle, Laure, Gervais, Anne, Sogni, Philippe, Salmon-Ceron, Dominique, Carrieri, Maria Patrizia, Group, the ANRS CO13-HEPAVIH Cohort Study, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), 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, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departamento de Vigilância, Prevenção e Controle das IST, do HIV/Aids e das Hepatites Virais [Brasília, Brazil], Ministério da Saúde [Brasília, Brazil]-Secretaria de Vigilância em Saúde [Brasília, Brazil], Programa de Pós-Graduação em Saúde Coletiva [Brasília, Brazil], Universidade de Brasilia [Brasília] (UnB)-Faculdade de Ciências da Saúde [Brasília, Brazil], Service d'information médicale, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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), 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), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the French National Agency for Research on Aids and Viral Hepatitis (ANRS), with the participation of Abbott France, Glaxo-Smith-Kline, Roche, Schering-Plough, and INSERM’s ‘Programme Cohortes TGIR’., 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 [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, 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), Service de Hépato-gastro-entérologie et cancérologie digestive [APHP Bichat Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and YAYA, Issifou

Subjects
Liver Cirrhosis, Male, Alcoholic liver disease, Liver fibrosis, Alcohol, HIV Infections, Logistic regression, Severity of Illness Index, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Medicine, HIV-HCV co-infection, Longitudinal Studies, Prospective Studies, ComputingMilieux_MISCELLANEOUS, liver fibrosis, Nutrition and Dietetics, Middle Aged, 3. Good health, Liver, 030220 oncology & carcinogenesis, Cohort, Disease Progression, 030211 gastroenterology & hepatology, Female, France, lcsh:Nutrition. Foods and food supply, Adult, Risk, medicine.medical_specialty, Alcohol Drinking, alcohol consumption, coffee, lcsh:TX341-641, Lower risk, Article, 03 medical and health sciences, Internal medicine, Coffee intake, Humans, Ethanol, business.industry, Hepatitis C, Chronic, medicine.disease, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Self Report, business, Biomarkers, Food Science
Abstract

International audience; BACKGROUND:Coffee intake has been shown to modulate both the effect of ethanol on serum GGT activities in some alcohol consumers and the risk of alcoholic cirrhosis in some patients with chronic diseases. This study aimed to analyze the impact of coffee intake and alcohol consumption on advanced liver fibrosis (ALF) in HIV-HCV co-infected patients.METHODS:ANRS CO13-HEPAVIH is a French, nationwide, multicenter cohort of HIV-HCV-co-infected patients. Sociodemographic, behavioral, and clinical data including alcohol and coffee consumption were prospectively collected using annual self-administered questionnaires during five years of follow-up. Mixed logistic regression models were performed, relating coffee intake and alcohol consumption to ALF.RESULTS:1019 patients were included. At the last available visit, 5.8% reported high-risk alcohol consumption, 27.4% reported high coffee intake and 14.5% had ALF. Compared with patients with low coffee intake and high-risk alcohol consumption, patients with low coffee intake and low-risk alcohol consumption had a lower risk of ALF (aOR (95% CI) 0.24 (0.12⁻0.50)). In addition, patients with high coffee intake had a lower risk of ALF than the reference group (0.14 (0.03⁻0.64) in high-risk alcohol drinkers and 0.11 (0.05⁻0.25) in low-risk alcohol drinkers).CONCLUSIONS:High coffee intake was associated with a low risk of liver fibrosis even in HIV-HCV co-infected patients with high-risk alcohol consumption.

Published
2018
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41. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author

Raymond, E, Nicot, F., Morand-Joubert, A, Rodallec, D, Mourez, M, Beby-Defaux, D, Lambert-Niclot, P, Charpentier, E, Malvé, B., Le Guillou-Guillemette, A, Si-Mohamed, D, Avettand Fenoel, A, Roussel, A., Calvez, P, Saune, E, Rodriguez, M, Descamps, E, Izopet, E, Lagier, E, Roussel, C, Le Guillou-Guillemette, G, Alloui, A., Bettinger, D., Pallier, P, Fleury, Frédéric, Reigadas, R, Bellecave, P., Recordon-Pinson, P, Payan, P, Vallet, S., Vabret, A., Dina, D, Henquell, C., Mirand, A., Bouvier-Alias, A, de Rougemont, A, Dos Santos, D, Morand, P, Signori-Schmuck, A., Bocket, B, Rogez, R, Andre, A, Tardy, C, Trabaud, A, Tamalet, C., Delamare, D, Montes, B, SCHVOERER, Evelyne, Ferré, F., André-Garnier, E., Cottalorda, C, Guinard, G, Guiguon, A, Descamps, D., Brun-Vézinet, B, Charpentier, c, Visseaux, B, Peytavin, G., Krivine, A., Si-Mohamed, A, Avettand-Fenoel, Véronique, Marcelin, A, Calvez, C, Lambert-Niclot, L, Soulié, C., Wirden, M., Morand-Joubert, M, Delaugerre, D, Chaix, M, Amiel, A, Schneider, S., Giraudeau, G, Beby- Defaux, D, Brodard, B, Maillard, A., Plantier, P, Chaplain, C, Bourlet, B, Fafi-Kremer, F, Stoll-Keller, F., Schmit, P, Barth, B, Yerly, S, Poggi, P., Izopet, I, Raymond, R, Barin, B, Chaillon, A, Marque-Juillet, M, Roque-Afonso, A, Haïm-Boukobza, B, Flandre, P., Grudé, G, Assoumou, A, Costagliola, D, Allegre, A, Schmit, J, Chennebault, M, Bouchaud, B, Magy-Bertrand, B, Delfraissy, D, Dupon, D, Morlat, P, Neau, D, Ansart, A., Jaffuel, J, Verdon, R, Jacomet, C, Lévy, L, Dominguez, D, Chavanet, P., Piroth, P, Cabié, A., Leclercq, P, Ajana, A, Cheret, A, Weinbreck, P, Cotte, C, Poizot-Martin, P, Ravaud, R., Christian, B, Truchetet, F, Grandidier, G, Rey, R., May, M, Goehringer, G, Raffi, F., Dellamonica, D, Prazuck, P, Hocqueloux, L, Landman, R, Yazdanpanah, Y., Launay, L, WEISS, L, Viard, P, Katlama, C., Simon, A., Girard, G, Meynard, M, Molina, M, Pialoux, G, Hoen, B., Goeger-Sow, G, Lamaury, I, Beaucaire, G, Le Moal, G., Jaussaud, R., Rouger, C, Michelet, M., Borsa-Lebas, B, Caron, F, Khuong, A., Lucht, F., Rey, D., Calmy, A, Lafeuillade, A, Marchou, B, Delobel, D, Gras, G, Greder-Belan, A, Vittecoq, D, Teiche, E, 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), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de virologie [CHU Toulouse], CHU Toulouse [Toulouse], Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universiatire Hôtel-Dieu de Nantes (CHU Hôtel-Dieu), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Rouen, Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Henri Mondor, CHU Pitié-Salpêtrière [AP-HP], 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), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Virologie [AP-HP Hôpital Bichat-Claude-Bernard], 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), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Clermont-Ferrand, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Necker, Centre Hospitalier Universitaire d'Amiens, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Agence Nationale de Recherches sur le SIDA et les hepatites virales (French National Agency for Research on AIDS and Viral Hepatitis, ANRS), Janssen-Cilag SAS, Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Pharmacologie Médicale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Faculté de Médecine/CHU, CHU Besançon, Université de Franche-Comté (UFC), Génétique et évolution des interactions hôtes-parasites, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Virologie Humaine et Moléculaire [Caen], Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Génomique et épigénétique des pathologies placentaires (Inserm U709), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Necker - Enfants Malades [AP-HP], Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroParisTech, T1, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences pour l'environnement (SPE), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Département d'infectiologie (CHU de Dijon), 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], Laboratoire d'Acoustique de l'Université du Mans (LAUM), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), ONERA - The French Aerospace Lab [Toulouse], ONERA, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), UMR CNRS 8179, Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine Interne, Maladies Infectieuses et Tropicales (POTIERS - Mal Inf), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University Hospital and University Jean Monnet, Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Maladies Infectieuses et Tropicales [CHU Poitiers], 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), Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital de la Pitié-Salpêtrière, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
0301 basic medicine, Male, Drug Resistance, HIV Infections, Drug resistance, Medical and Health Sciences, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2.1 Biological and endogenous factors, Viral, Aetiology, Articles and Commentaries, ComputingMilieux_MISCELLANEOUS, minority resistant variants, Viral Load, Biological Sciences, first-line antiretroviral therapy, 3. Good health, Infectious Diseases, Rilpivirine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV/AIDS, Female, Infection, Viral hepatitis, Viral load, Microbiology (medical), Adult, ultra-deep sequencing, Microbiology, Virus, rilpivirine, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Drug Resistance, Viral, Genetics, medicine, Humans, business.industry, Genetic Variation, medicine.disease, Virology, Reverse transcriptase, Regimen, Good Health and Well Being, 030104 developmental biology, chemistry, Mutation, HIV-1, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Antimicrobial Resistance, business
Abstract

Background Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR). Methods All the subjects, 541 HIV-1–infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load Results NGS revealed resistance-associated mutations accounting for 1% to 20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count Conclusions Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.

Published
2018
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42. Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

Author

Marc Bonnin, Nathalie Bendriss-Vermare, Ludovic Aillot, Sarah Maadadi, Caroline Scholtes, David Durantel, Isabel Najera, Fabien Zoulim, Julie Lucifora, Miroslava Subic, Malika Ait-Goughoulte, Laura Dimier, 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Département d'Hématologie [CHU Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Développement Cancer et Thérapies Ciblées / Cancer Development and Targeted Therapies (DEVweCAN LabEx), Université de Lyon - UDL, This work was supported by grants from ANRS (French national agency for research on AIDS and viral hepatitis), FINOVI (Foundation for innovation in infectiology), and INSERM. Besides academic funding, this work was mainly supported by Hoffmann-La Roche via its RPF (Roche Postdoc Fellowship) program, M. Bonnin was the recipient of this program under the supervision of D. Durantel (academic side) and M. Ait-Goughoulte/I. Najera (Roche scientist leaders)., ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Durantel, David, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, and PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID

Subjects
0301 basic medicine, Agonist, entry inhibition, HBsAg, CpG Oligodeoxynucleotide, medicine.drug_class, [SDV]Life Sciences [q-bio], Alpha interferon, chemical and pharmacologic phenomena, medicine.disease_cause, Antiviral Agents, Cell Line, 03 medical and health sciences, immune system diseases, parasitic diseases, medicine, Humans, Pharmacology (medical), Receptor, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, agonist, Pharmacology, Hepatitis B virus, plasmacytoid cells, Chemistry, Virion, TLR9, Interferon-alpha, hemic and immune systems, Toll-like receptor 9, Dendritic Cells, Molecular biology, digestive system diseases, 3. Good health, Toll-Like Receptor 9, Toll-like receptors, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oligodeoxyribonucleotides, plasmacytoid dendritic cells, hepatocytes, hepatitis B virus
Abstract

International audience; We previously reported that Toll-like receptor 9 (TLR9)-CpG oligonucleo-tides could inhibit the establishment of hepatitis B virus (HBV) infections in hepato-cytes. Our aim was to uncover the underlying mechanisms of this inhibition. HepaRG cells, RPMI-B lymphoblastoma cells, and primary plasmacytoid dendritic cells (pDCs) exposed to HBV and TLR9 ligands/agonists in various configurations were used. We observed an inhibition of HBV infection upon TLR9 stimulations only when agonist was applied during inoculation. This inhibition was independent of interleukin-6 (IL-6)/interferon-inducible protein 10 (IP-10) production as well as of TLR9 expression in hepatocytes. We further demonstrated an entry inhibition mechanism by showing a noncovalent binding of TLR9 agonist to HBV particles. Besides inhibiting HBV entry into hepatocytes, this biophysical interaction between HBV virions and TLR9 agonist was responsible for a reduction of alpha interferon (IFN-) expression by pDCs. Interestingly , subviral particles composed of only HBsAg were able to genuinely inhibit the TLR9 pathway, without titrating TLR9 ligands. To conclude, our data suggest that synthetic TLR9-CpG oligonucleotides can strongly inhibit HBV entry by " coating " HBV virions and thereby preventing their interaction with cellular receptor. This titration effect of TLR9 agonist is also artifactually responsible for the inhibition of TLR9 engagement in pDCs, whereas a genuine inhibition of this innate pathway was confirmed with HBsAg subviral particles. H epatitis B virus (HBV) chronically infects 240 million people worldwide and represents one of the major etiologies for cirrhosis and hepatocellular carcinoma (1, 2). The progression rate of chronicity is tightly linked with the maturity of the immune system, since 90 to 95% of infected newborns become chronic carriers, whereas only 5 to 10% of adults do (3). As HBV long-term persistence is characterized by subversion of both innate and adaptive immunity (4, 5), a better understanding of the underlying cellular and molecular mechanisms of this escape should help in defining new therapeutic strategies to reactivate the host immune system and control viral replication. Current front-line therapies include the use of nucleoside analogues to specifically inhibit viral reverse transcription and/or pegylated interferon alpha 2a or 2b (Peg-IFN

Published
2018
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43. Treatment interruption in HIV-positive patients followed up in Cameroon's antiretroviral treatment programme : individual and health care supply-related factors (ANRS-12288 EVOLCam survey)

Author

Christelle, Tong, Marie, Suzan-Monti, Luis, Sagaon-Teyssier, Mohamed, Mimi, Christian, Laurent, Gwenaëlle, Maradan, Marie-Thérèse, Mengue, Bruno, Spire, Christopher, Kuaban, Laurent, Vidal, Sylvie, Boyer, I, Seyep, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut de Recherche pour le Développement (IRD), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et 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), Université Catholique d'Afrique Centrale - Institut Catholique de Yaoundé (UCAC), Department of Internal Medicine and Subspecialties [Yaoundé, Cameroon], University of Yaoundé [Cameroun], This study was approved by the Cameroonian Ministry of Public Health and was financially supported by the French National Agency for Research on AIDS and viral hepatitis (ANRS)., EVOL Cam group, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er 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), and Lissalde, Claire

Subjects
0301 basic medicine, Program evaluation, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Tuberculosis, Cross-sectional study, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Developing country, HIV Infections, interruption du traitement antirétroviral, antiretroviral treatment interruption, health care supply-related factors, Logistic regression, Lower risk, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Health care, Medicine, Humans, 030212 general & internal medicine, Cameroon, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, 1. No poverty, Public Health, Environmental and Occupational Health, VIH, HIV, facteurs liés à l'offre des soins de santé, Patient Acceptance of Health Care, individual factors, medicine.disease, facteurs individuels, 030112 virology, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Cross-Sectional Studies, Family medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Population study, Patient Compliance, Parasitology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; introduction Decreasing international financial resources for HIV and increasing numbers of antiretroviral treatment (ART)-treated patients may jeopardise treatment continuity in low-income settings. Using data from the EVOLCam ANRS-12288 survey, this study aimed to document the prevalence of unplanned treatment interruption for more than 2 consecutive days (TI>2d) and investigate the associated individual and health care supply-related factors within the Cameroonian ART programme. methods A cross-sectional mixed methods survey was carried out between April and December 2014 in 19 HIV services of the Centre and Littoral regions. A multilevel logistic model was estimated on 1885 ART-treated patients in these services to investigate factors of TI>2d in the past 4 weeks. results Among the study population, 403 (21%) patients reported TI>2d. Patients followed up in hospitals reporting ART stock-outs were more likely to report TI>2d while those followed up in the Littoral region, in medium-or small-sized hospitals and in HIV services proposing financial support were at lower risk of TI>2d. The following individual factors were also associated with a lower risk of TI>2d: living in a couple, having children, satisfaction with attention provided by doctor, tuberculosis co-infection and not having consulted a traditional healer. conclusions Besides identifying individual factors of TI>2d, our study highlighted the role of health care supply-related factors in shaping TI in Cameroon's ART programme, especially the deleterious effect of ART stock-outs. Our results also suggest that the high proportion of patients reporting TI could jeopardise progress in the fight against HIV in the country, unless effective measures are quickly implemented like ensuring the continuity of ART supply. keywords HIV, Cameroon, antiretroviral treatment interruption, individual factors, health care supply-related factors

Published
2018
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44. Innovative community‐based educational face‐to‐face intervention to reduce HIV, hepatitis C virus and other blood‐borne infectious risks in difficult‐to‐reach people who inject drugs: results from the ANRS–AERLI intervention study

Author

Jean-Marie Le Gall, Marie Suzan-Monti, Marion Mora, Caroline Lions, Camelia Protopopescu, Perrine Roux, Marie Debrus, Maria Patrizia Carrieri, Bruno Spire, Khadim Ndiaye, Baptiste Demoulin, Aurelie Haas, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Marseille, France] (Association loi de 1901), Médecins du Monde [Paris, France] (Association médicale militante de solidarité internationale), French National Agency for Research for AIDS and Viral Hepatitis (ANRS)., and Lissalde, Claire

Subjects
Adult, Male, Program evaluation, medicine.medical_specialty, local complications, 030508 substance abuse, Medicine (miscellaneous), HIV Infections, Communicable Diseases, Education, 03 medical and health sciences, Risk-Taking, 0302 clinical medicine, Harm Reduction, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intervention (counseling), Cluster Analysis, Humans, Medicine, Community Health Services, injecting drug user, 030212 general & internal medicine, Substance Abuse, Intravenous, Health Education, intervention, Drug injection, Harm reduction, business.industry, HIV, Hepatitis C, medicine.disease, Checklist, 3. Good health, Psychiatry and Mental health, Telephone interview, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, HCV, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health education, France, 0305 other medical science, business, Social psychology, Program Evaluation
Abstract

Aims To study the effectiveness of an educational intervention on risks associated with drug injection, comparing primary [unsafe HIV–hepatitis C virus (HCV) practices] and secondary (local complications at injecting site) end-points in harm reduction (HR) programmes offering this intervention versus HR programmes not offering it. Design This non-random clustered intervention study was conducted in nine intervention groups (programmes offering the intervention) and eight control groups (programmes not offering it). Each participant was followed-up through a telephone interview at enrolment and at 6 and 12 months. Setting The study took place in 17 cities throughout France. Participants Of the 271 participants, 144 were enrolled into the intervention group and 127 in the control group. Of the latter, 113 received at least one educational session. Intervention A series of participant-centred face-to-face educational sessions. Each session included direct observation by trained non-governmental organization (NGO) staff or volunteers of participants’ self-injecting the psychoactive product they used habitually; analysis by the trained NGO staff or volunteers of the participant's injecting practices, identification of injection-related risks and explanation of safer injecting practices; and an educational exchange on the individual participant's injection practices and the questions he or she asked. Measurements Primary and secondary outcomes were ‘at least one unsafe HIV–HCV practice’ and at least one injection-related complication (derived from a checklist). Findings The proportion of participants with at least one unsafe HIV–HCV practice in the intervention group decreased significantly, from 44% at M0 to 25% at M6, as well as complications at the injection site (from 66 to 39% at M12), while in the control group it remained mainly stable. Multivariate probit analyses showed that the intervention group experienced a significant reduction in unsafe HIV–HCV practices at M6 [coefficient, 95% confidence interval (CI) = −0.73 (−1.47 to 0.01)] and in injection-related complications at M12 [coefficient, 95% CI = −1.01 (−1.77 to −0.24)], compared with the control group. Conclusions An inexpensive and easily implemented educational intervention on risks associated with drug injection reduces significantly unsafe HIV–HCV transmission practices and injection-related complications.

Published
2015
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45. Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection

Author

Beatrice Jacquelin, Alice Lepelley, Pierre Lebon, Steven E. Bosinger, Simon P. Jochems, Lise Chauveau, Mickaël J.-Y. Ploquin, Gaël Petitjean, Olivier Schwartz, Anne-Sophie Liovat, Michaela Müller-Trutwin, Nicolas Huot, Françoise Barré-Sinoussi, Emily K. Cartwright, Guido Silvestri, HIV, Inflammation et persistance, Institut Pasteur [Paris], Université Paris Diderot - Paris 7 (UPD7), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Régulation des Infections Rétrovirales, Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center [Lawrenceville, GA], Emory University [Atlanta, GA]-Emory University [Atlanta, GA], Non-Human Primate Genomics Core, Laboratoire de Virologie, Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), This work was supported by Fondation AREVA, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Sidaction, Fondation TOTAL (to F.B.-S.), the French Ministry of Higher Education and Research, and Institut Pasteur., Virus et Immunité, Institut Pasteur [Paris] - Université Paris Diderot - Paris 7 (UPD7) - Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Yerkes National Primate Research Center, Hôpital Saint-Vincent de Paul - Université Paris Descartes - Paris 5 (UPD5), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
Receptors, CCR5, viruses, Immunology, Heterologous, Inflammation, macromolecular substances, Plasmacytoid dendritic cell, medicine.disease_cause, Microbiology, Macaque, Cercocebus atys, 03 medical and health sciences, Immune system, Interferon, Virology, biology.animal, Chlorocebus aethiops, medicine, Animals, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, 030306 microbiology, virus diseases, hemic and immune systems, Dendritic Cells, Virus Internalization, Simian immunodeficiency virus, 3. Good health, Insect Science, CD4 Antigens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pseudotyping, Pathogenesis and Immunity, Simian Immunodeficiency Virus, medicine.symptom, medicine.drug
Abstract

Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4 + T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV in vivo identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor. IMPORTANCE The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I interferon (IFN-I) upon heterologous SIVmac/HIV type 1 (HIV-1) encounter, while they sensed autologous SIVagm isolates. Pseudotyping SIVmac/HIV-1 overcame this deficiency, suggesting that reduced uptake of heterologous viral strains underlays this lack of sensing. The distinct IFN-I responses depending on host species and HIV/SIV isolates reveal the host/virus species specificity of pDC sensing.

Published
2015
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46. Profil, pratiques à risques et besoins des personnes qui injectent du sulfate de morphine : Résultats de l'étude ANRS-AERLI

Author

Patrizia Carrieri, Salim Mezaache, Camelia Protopopescu, Perrine Roux, Marie Debrus, Laélia Briand-Madrid, Daniela Rojas-Castro, Nicolas Khatmi, Gwenaëlle Maradan, Mezaache, Salim, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Pantin, France], Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Médecins du Monde [Paris, France] (Association médicale militante de solidarité internationale), and This study received external funding from the French National Agency for Research for AIDS and Viral Hepatitis (ANRS).

Subjects
Adult, Male, Narcotics, medicine.medical_specialty, Multivariate analysis, Morphine sulfate, 030508 substance abuse, Medicine (miscellaneous), 03 medical and health sciences, 0302 clinical medicine, Risk practices, Community-based research, Intervention (counseling), Internal medicine, medicine, Opiate Substitution Treatment, Humans, 030212 general & internal medicine, Longitudinal Studies, Substance Abuse, Intravenous, Volunteer, Drug injection, Harm reduction, Morphine, business.industry, Health Policy, Educational intervention, digestive system diseases, 3. Good health, Buprenorphine, Opioid, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, 0305 other medical science, business, Methadone, Needs Assessment, medicine.drug
Abstract

Aims In France, a non-negligible proportion of opioid-dependent individuals inject morphine sulfate. Although it has not yet been officially approved as an opioid substitution treatment (OST), some physicians can prescribe its use for people in methadone or buprenorphine treatment failure. Longitudinal data from the ANRS-AERLI study, which evaluated an educational intervention for safer injection called AERLI, provided us the opportunity to better characterize the profile, risk practices and needs of people who inject morphine sulfate (MSI), through comparison with other injectors, and to identify correlates of HIV/HCV risk practices in this group. Methods The national multisite ANRS-AERLI study assessed the impact of AERLI offered in volunteer harm reduction (HR) centers (“with intervention”) (n = 113) through comparison with standard HR centers (“without intervention”) (n = 127). All participants were scheduled to be followed up for 12 months and have 3 telephone interviews: at baseline, 6 months and 12 months. We compared MSI (n = 79) with other opioid injectors (n = 161) and then used a mixed logistic model to identify factors associated with HIV/HCV risk practices among MSI. Findings Of the 240 eligible participants, 79 were regular MSI. They were less likely to use cocaine, crack or buprenorphine and to receive OST than other participants. Conversely, MSI were more likely to inject drugs more than three times a day and to report HIV/HCV risk practices. Among MSI, multivariate analysis showed that those receiving morphine sulfate as an OST were less likely to report such practices than other participants (aOR [95%CI] = 0.11 [0.02-0.61]). Conclusion Our results show that while MSI use fewer stimulants, they have more HIV/HCV risk practices than other injectors. However, when MSI are prescribed morphine sulfate as a treatment, these practices tend to decrease. Our findings suggest the importance of increasing access to morphine sulfate as a new OST in France.

Published
2018
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47. Interaction study between HCV NS5A-D2 and NS5B using 19F NMR

Author

Guy Lippens, Xavier Hanoulle, Marie Dujardin, François-Xavier Cantrelle, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), ANR-11-JSV8-005, French National Agency for Research on AIDS and Viral Hepatitis [A02014-2], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), ANR-11-JSV8-0005,StruFunc5A5B,Etude des relations structurales et fonctionnelles entre les protéines NS5A et NS5B du virus de l'hépatite C et la Cyclophiline A humaine.(2011), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Stereochemistry, Hepatitis C virus, viruses, [SDV]Life Sciences [q-bio], constante de dissociation, RNA-dependent RNA polymerase, HCV NS5A-D2, Fluorine-19 NMR, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Protein–protein interaction, protéine non structurale, 03 medical and health sciences, chemistry.chemical_compound, arn, labelling method, medicine, méthode de marquage, Surface plasmon resonance, hepatitis c, NS5A, NS5B, Spectroscopy, réplication, 19F protein labelling, 19F NMR spectroscopy, RNA, virus diseases, biochemical phenomena, metabolism, and nutrition, digestive system diseases, hépatite c, 0104 chemical sciences, 3. Good health, HCV NS5B, 030104 developmental biology, chemistry
Abstract

The non structural protein 5A (NS5A) regulates the replication of the hepatitis C viral RNA through a direct molecular interaction of its domain 2 (NS5A-D2) with the RNA dependent RNA polymerase NS5B. Because of conflicting data in the literature, we study here this molecular interaction using fluorinated versions of the NS5A-D2 protein derived from the JFH1 Hepatitis C Virus strain. Two methods to prepare fluorine-labelled NS5A-D2 involving the biosynthetic incorporation of a F-19-tryptophan using 5-fluoroindole and the posttranslational introduction of fluorine by chemical conjugation of 2-iodo-N-(trifluoromethyl)acetamide with the NS5A-D2 cysteine side chains are presented. The dissociation constants (K-D) between NS5A-D2 and NS5B obtained with these two methods are in good agreement, and yield values comparable to those derived previously from a surface plasmon resonance study. We compare benefits and limitations of both labeling methods to study the interaction between an intrinsically disordered protein and a large molecular target by F-19 NMR.

Published
2018
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48. Impact of an educational intervention on risks associated with drug injection, and on psychosocial factors (PSF) involved in initiating and maintaining new health behaviors over time

Author

Daniela Rojas Castro, Lionel Dany, Perrine Roux, Khadim Ndiaye, Patrizia Carrieri, Nicolas Khatmi, Dupuis, Christine, Laboratoire de Psychologie Sociale (LPS), Aix Marseille Université (AMU), 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), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), AIDES [Pantin, France] (Mission Innovation Recherche Expérimentation), and This study received external funding from the French National Agency for Research for AIDS and Viral Hepatitis (ANRS).

Subjects
Adult, Male, media_common.quotation_subject, Health Behavior, Medicine (miscellaneous), Intervention, Toxicology, Injecting drug user, Developmental psychology, Self-Control, 03 medical and health sciences, 0302 clinical medicine, Risk-Taking, Health care, medicine, Humans, 030212 general & internal medicine, Substance Abuse, Intravenous, Competence (human resources), Health Education, media_common, 030505 public health, business.industry, Addiction, Psychosocial factor, Social environment, HIV, medicine.disease, Self-determination, Self Concept, Substance abuse, Psychiatry and Mental health, Clinical Psychology, Treatment Outcome, Feeling, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HCV, Educational Status, Patient Compliance, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, business, Psychology, Psychosocial, Risk Reduction Behavior, Autonomy
Abstract

Background/aims In line with Self-determination Theory, individuals who feel they are able to adopt new behaviors autonomously, and who perceive their social environment as supportive of their autonomy and confident in their competencies, are more likely to engage in sustainable behavioral change over time. We aimed to study the impact of an educational intervention, which has already shown its effectiveness in reducing transmission-risk behaviors and injection-related complications among drug users (Roux et al., 2016), on three psychosocial factors (PSF) involved in initiating and maintaining new health behaviors over time, as follows: A) self-regulation of behaviors (autonomous vs. controlled regulation); B) perceived competence in adopting new behaviors (a feeling of being able or unable to adopt new behaviors) and C) perceived autonomy support (social environment perceived by drug users as supportive of autonomy vs. controlling). Methods This non-random clustered intervention study was conducted in 9 intervention groups (programs offering the intervention) and 8 control groups (programs not offering it). Each participant was followed up through a phone interview at enrolment, at 6 months and 12 months. Of the 271 participants, 113 received at least one educational session in the first six months. We used the “Health-Care Self-Determination Theory Questionnaire” to assess the impact of this intervention on the development of self-regulation, perceived competence and perceived autonomy support. Results Participants exposed to the intervention at least once were associated with a higher level of perceived competence and perceived autonomy support at M12. However, the intervention did not impact self-regulation (either autonomous or controlled). In addition, the study revealed that other factors, such as gender, age, drug use patterns and participants' healthcare pathways, also have an impact on these PSF. Conclusions This educational intervention significantly increases patients' perceived competence but has no impact on the factors specifically involved in maintaining new behaviors over time. This study also highlights the existence of user profiles whose socio-demographic characteristics, use patterns and care pathways can influence these FPS involved in motivation to change and maintain new health behaviors over time.

Published
2018
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49. Changes in supervised drug-injecting practices following a community-based educational intervention: A longitudinal analysis

Author

Mezaache, Salim, Protopopescu, Camelia, Debrus, Marie, Morel, Stéphane, Mora, Marion, Suzan-Monti, Marie, Rojas Castro, Daniel, Carrieri, Patrizia, Roux, Perrine, Mezaache, Salim, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Médecins du Monde [Paris, France] (Association médicale militante de solidarité internationale), AIDES [Pantin, France], Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Coalition PLUS [Pantin, France], and This study received external funding from the French National Agency for Research for AIDS and Viral Hepatitis (ANRS).

Subjects
Harm reduction, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Skin and soft tissue infections, Injecting drug use, Intervention, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Injecting practices, Education
Abstract

International audience; BACKGROUND:People who inject drugs face several health issues because of unsafe injecting practices. We aimed to evaluate changes in supervised drug-injecting practices following the implementation of a face-to-face educational intervention.METHODS:The national study ANRS-AERLI was conducted in 17 harm reduction (HR) facilities in France between 2011 and 2013. Eight offered the intervention and nine did not. We conducted a pre-post analysis focusing on injecting practices data, collected in the 8 HR facilities providing the intervention. The intervention consisted of providing face-to-face educational sessions including direct observation of injecting practices, counseling about safer injecting, and shared discussion. Injecting practices were collected following a checklist and classified as safe or unsafe. To assess changes in injecting practices, practices were compared before (at baseline) and after at least one educational session.FINDINGS:Mixed logistic models showed that the 78 participants included were more likely to improve in the following drug-use steps: setting up a clean preparation area (Adjusted Odds Ratio (AOR) = 3.4, 95% Confidence Interval (95% CI) = 1.6-7.6), hand washing (AOR = 7.2, 95% CI = 3.1-16.4), skin cleaning (AOR = 5.6, 95% CI = 2.5-12.1), choice of safe injection site (AOR = 6.5, 95% CI = 1.5-28.8) and post-injection bleeding management (AOR = 12.8, 95% CI = 5.5-29.9). Furthermore, participants were less likely to lick their needles before injecting (AOR = 8.1, 95% CI = 1.5-43.4) and to perform booting/flushing (AOR = 2.5, 95% CI = 1.2-5.3).CONCLUSIONS:The AERLI intervention seems to be effective in increasing safe drug-injecting practices.

Published
2018
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50. Identification of Piperazinylbenzenesulfonamides as New Inhibitors of Claudin-1 Trafficking and Hepatitis C Virus Entry

Author

Sandrine Belouzard, Jens Bukh, Lucie Fénéant, Priscille Brodin, Yves Rouillé, Jean Dubuisson, Laura Riva, Thomas F. Baumert, Alexandre Vandeputte, François Helle, Jannick Prentoe, Laurent L'homme, Laurence Cocquerel, Charles-Henry Gattolliat, Ok-Ryul Song, Tarik Asselah, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Copenhagen Hepatitis C Program [Copenhague, Danemark] (CO-HEP), Hvidovre Hospital-University of Copenhagen = Københavns Universitet (UCPH), Unité de Virologie clinique et fondamentale (UVCF), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de Lille - UMS 3702 (IBL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and the ANR through the ERA-NET Infect-ERA program (grant ANR-13-IFEC-0002-01). In addition, this study was supported by research grants from the Danish Council for Independent Research-Medical Sciences and the Novo Nordisk Foundation. The BioImaging Center Lille Nord-de-France is supported by the Equipex IMAGINEX program., The Copenhagen Hepatitis C Program (CO-HEP) is a joint venture of the Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital, and the Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. We thank F. L. Cosset, C. Rice, and T. Wakita for providing essential reagents. We also thank S. Ung for his help in preparing the figures and L. Linna for manuscript proofreading. We are very grateful to A. Danneels for her precious help during the revisions. Immunofluorescence and flow cytometry analyses were performed with the help of the imaging core facility of the BioImaging Center Lille Nord-de-France., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of Copenhagen = Københavns Universitet (KU)-Hvidovre Hospital, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Dubuisson, Jean, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (KU), Unité de Virologie clinique et fondamentale EA 4294, Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI), Hôpital Beaujon, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon

Subjects
0301 basic medicine, tight junction protein, hepatitis C virus, Cell, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Hepacivirus, virus entry, medicine.disease_cause, MESH: Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors, Piperazines, Receptors, G-Protein-Coupled, MESH: Virus Internalization/drug effects, MESH: Isoquinolines/pharmacology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Claudin-1, MESH: Receptors, Serotonin/metabolism, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sulfonamides, MESH: Claudin-1/metabolism, MESH: Cyclic AMP-Dependent Protein Kinases/metabolism, MESH: Protein Transport/drug effects, MESH: Protein Kinase Inhibitors/pharmacology, 3. Good health, Cell biology, Transport protein, Virus-Cell Interactions, MESH: Tetraspanin 28/metabolism, Protein Transport, medicine.anatomical_structure, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intracellular, MESH: Cell Line, Tumor, Hepatitis C virus, 030106 microbiology, Immunology, MESH: Sulfonamides/pharmacology, MESH: Tight Junctions/metabolism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Piperazines/pharmacology, Microbiology, Virus, piperazinylbenzenesulfonamide, Tetraspanin 28, Tight Junctions, 03 medical and health sciences, Viral entry, MESH: Receptors, G-Protein-Coupled/metabolism, Virology, Cell Line, Tumor, MESH: Hepacivirus/physiology, medicine, Humans, Protein kinase A, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Protein Kinase Inhibitors, MESH: Humans, virus-host interaction, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Virus Internalization, Isoquinolines, Cyclic AMP-Dependent Protein Kinases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, Insect Science, MESH: Hepatocytes/virology, Receptors, Serotonin, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Hepatocytes, protein kinase A, CD81
Abstract

Hepatitis C virus (HCV) infection causes 500,000 deaths annually, in association with end-stage liver diseases. Investigations of the HCV life cycle have widened the knowledge of virology, and here we discovered that two piperazinylbenzenesulfonamides inhibit HCV entry into liver cells. The entry of HCV into host cells is a complex process that is not fully understood but is characterized by multiple spatially and temporally regulated steps involving several known host factors. Through a high-content virus infection screening analysis with a library of 1,120 biologically active chemical compounds, we identified SB258585, an antagonist of serotonin receptor 6 (5-HT6), as a new inhibitor of HCV entry in liver-derived cell lines as well as primary hepatocytes. A functional characterization suggested a role for this compound and the compound SB399885, which share similar structures, as inhibitors of a late HCV entry step, modulating the localization of the coreceptor tight junction protein claudin-1 (CLDN1) in a 5-HT6-independent manner. Both chemical compounds induced an intracellular accumulation of CLDN1, reflecting export impairment. This regulation correlated with the modulation of protein kinase A (PKA) activity. The PKA inhibitor H89 fully reproduced these phenotypes. Furthermore, PKA activation resulted in increased CLDN1 accumulation at the cell surface. Interestingly, an increase of CLDN1 recycling did not correlate with an increased interaction with CD81 or HCV entry. These findings reinforce the hypothesis of a common pathway, shared by several viruses, which involves G-protein-coupled receptor-dependent signaling in late steps of viral entry. IMPORTANCE The HCV entry process is highly complex, and important details of this structured event are poorly understood. By screening a library of biologically active chemical compounds, we identified two piperazinylbenzenesulfonamides as inhibitors of HCV entry. The mechanism of inhibition was not through the previously described activity of these inhibitors as antagonists of serotonin receptor 6 but instead through modulation of PKA activity in a 5-HT6-independent manner, as proven by the lack of 5-HT6 in the liver. We thus highlighted the involvement of the PKA pathway in modulating HCV entry at a postbinding step and in the recycling of the tight junction protein claudin-1 (CLDN1) toward the cell surface. Our work underscores once more the complexity of HCV entry steps and suggests a role for the PKA pathway as a regulator of CLDN1 recycling, with impacts on both cell biology and virology.

Published
2017
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