Author: "French National Agency for Research on AIDS and Viral Hepatitis" / Language: english - Searchworks@Jio Institute Digital Library Search Results

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

1. National Cohort of Uncomplicated Alcoholic Cirrhosis (CIRRAL)

Author: National Cancer Institute, France and French National Agency for Research on AIDS and Viral Hepatitis
Published: 2019

2. The Microvascular Brain Retina And Kidney Study (MICROBREAK2)

Author: French National Agency for Research on AIDS and Viral Hepatitis
Published: 2018

3. 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

4. Vaccination of HIV-1 Infected Patients With Dendritic Cells in Addition to Antiretroviral Treatment - (DALIA Trial)

Author: French National Agency for Research on AIDS and Viral Hepatitis
Published: 2017

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

Author: French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO Study Group, Stefic, Karl, Novelli, Sophie, Mahjoub, Nadia, Seng, Remonie, Molina, Jean-Michel, Cheneau, Christine, Barin, Francis, Chaix, Marie-Laure, Meyer, Laurence, and Delaugerre, Constance
Published: 2018

6. 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

7. 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

8. 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

9. 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

10. 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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11. 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: RILPIVIRINE, VIROLOGY, REVERSE transcriptase, DRUG resistance, GENOTYPES
Abstract: Objectives: To 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 Methods: Four 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.Results: The mutational load at baseline was the only variable linked to the VR at 12 months (P < 0.01). The VR at 12 months decreased from 96.9% to 83.4% when the mutational load was >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).Conclusions: There 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 < 20% together with the plasma HIV-1 viral load at the time of resistance genotyping. [ABSTRACT FROM AUTHOR]
Published: 2019
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12. 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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13. 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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14. 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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15. Clinical Trial to Assess the Efficacy of Darunavir/Ritonavir (DRV/r), Etravirine (ETV) and Raltegravir (MK-0518) in HIV Patients With Resistant Viruses (ANRS139 TRIO)

Author: Merck Sharp & Dohme LLC, Janssen-Cilag Tibotec, and French National Agency for Research on AIDS and Viral Hepatitis
Published: 2010

16. 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. 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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27. 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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28. 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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29. 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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30. 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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31. 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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32. 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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33. 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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34. 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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35. 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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36. 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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37. 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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38. NOX2-dependent ATM kinase activation dictates pro-inflammatory macrophage phenotype and improves effectiveness to radiation therapy

Author: Laurent Voisin, Céline Leteur, Fabien Milliat, Eric Deutsch, Qiuji Wu, Eric Solary, Zeinaf Muradova, Haithem Dakhli, Audrey Paoletti, Awatef Allouch, Jean-Luc Perfettini, Filippo Rosselli, Frédéric Law, Mélanie Gauthier, David M. Ojcius, Maxime Thoreau, Elodie Mintet, Nazanine Modjtahedi, Olivier Caron, Isabelle Martins, Céline Mirjolet, Radiothérapie moléculaire (UMR 1030), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), 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 de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de radioprotection et de sûreté nucléaire [Fontenay-aux-Roses] (IRSN), Ministère de l'économie, de l'industrie et de l'emploi-Ministère de la Défense-Ministère de la santé-Ministère de l'Enseignement Supérieur et de la Recherche Scientifique-Ministère de l'écologie de l'Energie, du Développement durable et de l'Aménagement du territoire, University of California [Merced], University of California, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiothérapie moléculaire [UMR 1030], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL], Institut Jacques Monod [IJM (UMR_7592)], Institut Cochin [IC UM3 (UMR 8104 / U1016)], Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 [CRIStAL], University of California [Merced] [UC Merced], Stabilité Génétique et Oncogenèse [UMR 8200], Apoptose, cancer et immunité [U848], Institut Gustave Roussy (IGR), Systerel, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Laboratoire de Radiopathologie, Génomes et cancer (GC (FRE2939)), Hématopoïèse normale et pathologique, 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), 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.), Electricité de France and Fondation Gustave Roussy (to ED). QW is recipient of PhD fellowship of China Scholarship Council. AP and AA are, respectively, recipient of PhD fellowship and post-doc fellowship from Agence Nationale de Recherche sur le Sida et sur les Hépatites (ANRSH). LV and FL are recipient of PhD fellowships from Fondation pour la Recherche Médicale and CIFRE. HD, EM and MT are supported by the Laboratory of Excellence LERMIT with a grant from ANR (ANR-10-LABX-33) under the program ‘Investissements d'Avenir’ ANR-11-IDEX-0003-01. IM is funded by INCA (INCA-DGOS-INSERM 6043). CM work was supported by the ‘Cancéropôle Grand Est’, and the ‘Conseils Régionaux de Bourgogne, de Franche Comté et de Lorraine’., We gratefully acknowledge S Solier, Y Lecluse and S Salome-Desnoulez for technical support., Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille, and Ministère de l'écologie de l'Energie, du Développement durable et de l'Aménagement du territoire-Ministère de la santé-Ministère de la Défense-Ministère de l'Enseignement Supérieur et de la Recherche Scientifique-Ministère de l'économie, de l'industrie et de l'emploi
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Ataxia Telangiectasia Mutated Proteins, Neurodegenerative, Medical and Health Sciences, Mice, 0302 clinical medicine, Macrophage, Phosphorylation, ComputingMilieux_MISCELLANEOUS, Cancer, Microscopy, NADPH oxidase, biology, Kinase, Biological Sciences, Flow Cytometry, 3. Good health, Cell biology, 030220 oncology & carcinogenesis, Signal transduction, Signal Transduction, Biochemistry & Molecular Biology, Fluorescence, Cell Line, 03 medical and health sciences, Interferon-gamma, Ataxia Telangiectasia, Rare Diseases, Genetics, Animals, Humans, Molecular Biology, Protein Processing, Original Paper, Macrophages, Post-Translational, Cell Biology, Macrophage Activation, 030104 developmental biology, RAW 264.7 Cells, Microscopy, Fluorescence, Apoptosis, biology.protein, Cancer research, Protein Processing, Post-Translational, IRF5, Interferon regulatory factors
Abstract: International audience; Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here we show that ionizing radiation induces the expression of interferon regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. We reveal that the activation of the ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with γ-interferon, lipopolysaccharide or chemotherapeutic agent (such as cisplatin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a pro-inflammatory phenotype through the regulation of mRNA level and post-translational modifications of IRF5. We further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process. We also report that the inhibition of any component of this signaling pathway (NOX2, ROS and ATM) impairs pro-inflammatory activation of macrophages and predicts a poor tumor response to preoperative radiotherapy in locally advanced rectal cancer. Altogether, our results identify a novel signaling pathway involved in macrophage activation that may enhance the effectiveness of radiotherapy through the reprogramming of tumor-infiltrating macrophages.
Published: 2017
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39. Entry and Release of Hepatitis C Virus in Polarized Human Hepatocytes

Author: Yves Rouillé, Jean Dubuisson, Karin Seron, Adeline Danneels, Lucie Fénéant, Sandrine Belouzard, 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), This work was supported by a Marie Curie International Reintegration Grant (PIRG-GA-2009-256300) and by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and the ANR through the ERA-NET Infect-ERA program (ANR-13-IFEC-0002-01)., We thank F. L. Cosset, C. M. Rice, V. Thiel, and T. Wakita for providing essential reagents. The immunofluorescence analyses were performed with the help of the imaging core facility of the BioImaging Center, Lille, Nord-de-France., 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), 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, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: 0301 basic medicine, hepatitis C virus, Hepatitis C virus, [SDV]Life Sciences [q-bio], Immunology, Cell, Biology, virus entry, medicine.disease_cause, Microbiology, Virus, 03 medical and health sciences, 0302 clinical medicine, Viral entry, Virology, Cell polarity, medicine, Secretion, Author Correction, virus egress, 3. Good health, Cell biology, Virus-Cell Interactions, cell polarity, 030104 developmental biology, medicine.anatomical_structure, Cell culture, Insect Science, 030211 gastroenterology & hepatology, CD81
Abstract: Hepatitis C virus (HCV) primarily infects hepatocytes, which are highly polarized cells. The relevance of cell polarity in the HCV life cycle has been addressed only in distantly related models and remains poorly understood. Although polarized epithelial cells have a rather simple morphology with a basolateral and an apical domain, hepatocytes exhibit complex polarization structures. However, it has been reported that some selected polarized HepG2 cell clones can exhibit a honeycomb pattern of distribution of the tight-junction proteins typical of columnar polarized epithelia, which can be used as a simple model to study the role of cell polarization in viral infection of hepatocytes. To obtain similar clones, HepG2 cells expressing CD81 (HepG2-CD81) were used, and clones were isolated by limiting dilutions. Two clones exhibiting a simple columnar polarization capacity when grown on a semipermeable support were isolated and characterized. To test the polarity of HCV entry and release, our polarized HepG2-CD81 clones were infected with cell culture-derived HCV. Our data indicate that HCV binds equally to both sides of the cells, but productive infection occurs mainly when the virus is added at the basolateral domain. Furthermore, we also observed that HCV virions are released from the basolateral domain of the cells. Finally, when polarized cells were treated with oleic acid and U0126, a MEK inhibitor, to promote lipoprotein secretion, a higher proportion of infectious viral particles of lower density were secreted. This cell culture system provides an excellent model to investigate the influence of cell polarization on the HCV life cycle. IMPORTANCE Hepatitis C is a major health burden, with approximately 170 million persons infected worldwide. Hepatitis C virus (HCV) primarily infects hepatocytes, which are highly polarized cells with a complex organization. The relevance of cell polarity in the HCV life cycle has been addressed in distantly related models and remains unclear. Hepatocyte organization is complex, with multiple apical and basolateral surfaces. A simple culture model of HepG2 cells expressing CD81 that are able to polarize with unique apical and basolateral domains was developed to study HCV infection. With this model, we demonstrated that HCV enters and exits hepatocytes by the basolateral domain. Furthermore, lower-density viral particles were produced under conditions that promote lipoprotein secretion. This cell culture system provides a useful model to study the influence of cell polarization on HCV infection.
Published: 2017
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40. Self-Reported Bothersome Symptoms Across Different Socioepidemiological Groups of People Living With HIV Attending French Hospitals: Results From the ANRS-VESPA2 Survey

Author: Véronique Boyer, Antoine Vilotitch, Fabienne Marcellin, Baptiste Demoulin, Rosemary Dray-Spira, Bruno Spire, France Lert, Maria Patrizia Carrieri, Christine Hamelin, Nicolas Lorente, Marie Préau, Marie Suzan-Monti, Martin Duracinsky, Marion Mora, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), 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), French National Agency for Research on Aids and Viral Hepatitis (ANRS) (ANRS-EN12), Lissalde, Claire, Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and 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)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, Adolescent, Anti-HIV Agents, Population, Human immunodeficiency virus (HIV), Context (language use), HIV Infections, Comorbidity, medicine.disease_cause, Social group, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Moderate number, education, Psychiatry, Self report, General Nursing, education.field_of_study, General symptoms, business.industry, 1. No poverty, Middle Aged, self-report, 030112 virology, 3. Good health, Anesthesiology and Pain Medicine, Logistic Models, Socioeconomic Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, socioepidemiological group, symptoms, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, Self Report, business, ART
Abstract: Context Twenty years after the advent of combined antiretroviral therapies (ARTs), there is a growing need for up-to-date information about the daily experience of people living with HIV (PLWH). Objectives This study aimed to investigate the relationship between socioepidemiological groups and the types of bothersome symptoms reported by PLWH participating in a national survey in France. Methods We analyzed self-reported bothersome symptoms in a representative sample of PLWH (ANRS-VESPA2 survey), most of whom were receiving ART treatment. PLWH ( N = 2505) were grouped into three clusters according to the number of bothersome symptoms reported: Cluster A (low number, n = 1848), Cluster B (moderate number, n = 271), and Cluster C (high number, n = 386). Results Individuals in Cluster A (low number of bothersome symptoms) were less likely to report all the symptom types investigated. Psychological, sexual, and general symptoms were more likely to be reported in Cluster B (moderate number), whereas gastric-, pain-, and appearance-related symptoms were more likely in Cluster C (high number). In multivariate analyses, women not natives of Sub-Saharan Africa and former/active female injecting drug users were more likely to report a medium or high number of symptoms, and lower adherence to ART. Conclusion Combining new biomedical strategies with coping mechanisms and providing better support to socially vulnerable PLWH may improve this population's quality of health and daily life.
Published: 2017
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41. Population Pharmacokinetic Modeling of Tenofovir in the Genital Tract of Male HIV-Infected Patients

Author: Saïk Urien, Déborah Hirt, Marie Suzan-Monti, Jade Ghosn, Christine Rouzioux, Elodie Valade, Lambert Assoumou, Sílvia M. Illamola, Frantz Foissac, Jean-Marc Tréluyer, Maïlys De Sousa Mendes, Sihem Benaboud, Gabrielle Lui, Naïm Bouazza, Jean-Paul Viard, Aurélie Cobat, Camille Chenevier-Gobeaux, Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], CTG repeat instability and myotonic dystrophy (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM), UF de Thérapeutique en Immuno‑Infectiologie [AP-HP Hôtel Dieu], Hôpital Hôtel-Dieu [Paris], Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) sponsored the Evarist study. This study also received financial support from SIDACTION., Assistance publique - Hôpitaux de Paris (AP-HP) (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), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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 Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Lissalde, Claire
Subjects: 0301 basic medicine, Male, Physiology, Gene Expression, HIV Infections, population pharmacokinetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Blood plasma, Medicine, Pharmacology (medical), Drug Dosage Calculations, education.field_of_study, Liter, Middle Aged, HIV Reverse Transcriptase, Markov Chains, Infectious Diseases, Area Under Curve, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Monte Carlo Method, medicine.drug, Adult, Tenofovir, Anti-HIV Agents, Population, Biological Availability, Single-nucleotide polymorphism, Semen, Microbial Sensitivity Tests, Genitalia, Male, Polymorphism, Single Nucleotide, Drug Administration Schedule, 03 medical and health sciences, Pharmacokinetics, Humans, education, Pharmacology, Models, Statistical, business.industry, Body Weight, Bayes Theorem, genital tract, 030112 virology, tenofovir, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, seminal plasma, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Pharmacogenetics
Abstract: The aims of this study were to describe the blood plasma (BP) and seminal plasma (SP) pharmacokinetics of tenofovir (TFV) in HIV-1-infected men, to assess the role of genetic polymorphism in the variability of TFV transfer into the male genital tract, and to evaluate the impact of TFV SP exposure on seminal plasma HIV load (spVL). Men from the Evarist-ANRS EP 49 study treated with TFV as part of their antiretroviral therapy were included in the study. A total of 248 and 217 TFV BP and SP concentrations from 129 men were available for the analysis. For pharmacogenetic assessment, a total of 121 single nucleotide polymorphisms (SNP) were genotyped. Data were analyzed using a nonlinear mixed-effects modeling approach. TFV pharmacokinetics were best described by a two-compartment model for BP and by an effect compartment with different input and output constants for SP. TFV exposures (area under the concentration-time curve from 0 to 24 h [AUC 0–24 ]) were higher in SP than in BP (median AUC 0–24 , 7.01 versus 2.97 mg · liter −1 · h, respectively). The median (range) SP-to-BP AUC 0–24 ratio was 2.24 (0.53 to 34.13). After correction for multiple testing, none of the SNPs were significantly associated with the TFV transfer rate constant. The impact of the TFV SP AUC 0–24 or TFV SP-to-BP AUC 0–24 ratio on spVL was not significant ( P = 0.808 and 0.768, respectively). This is the first population model describing TFV pharmacokinetics in the male genital tract. TFV SP concentrations were higher than BP concentrations. Despite TFV SP exposures being higher than BP exposures, an spVL was detectable for 12.2% of the men.
Published: 2017
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42. Clinical development of hepatitis C virus host-targeting agents

Author: Thomas F. Baumert, Mirjam B. Zeisel, Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Université de Strasbourg (UNISTRA), Pôle hépato-digestif, Nouvel Hôpital Civil, Hospices Civils de Strasbourg-Institut Hospitalo-Universitaire de strasbourg, Grant support from the European Union, NIH, the French National Agency for Research on AIDS and Viral Hepatitis, the French Research Agency, and the French Foundation for Cancer Research (ARC)., and Zeisel, Mirjam
Subjects: 0301 basic medicine, biology, business.industry, Host (biology), Hepatitis C virus, Hepacivirus, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, Hepatitis C, medicine.disease, medicine.disease_cause, biology.organism_classification, Virology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Article, 03 medical and health sciences, 030104 developmental biology, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience;
Published: 2017
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43. The impact of coffee consumption on fibrosis and steatosis in HIV-HCV co-infected patients

Author: Maria Patrizia Carrieri, Laure Esterle, Fabienne Marcellin, Philippe Sogni, Dominique Salmon-Ceron, Camelia Protopopescu, Karine Lacombe, Linda Wittkop, Lissalde, Claire, 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), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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, ScheringPlough, and INSERM’s ‘Programme Cohortes TGIR’., Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: 0301 basic medicine, Hepatology, business.industry, Human immunodeficiency virus (HIV), Coffee consumption, Hepatitis C, medicine.disease, medicine.disease_cause, Virology, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Fibrosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, medicine, Coinfection, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Steatosis, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2017
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44. Decrease in self-reported offences and incarceration rates during methadone treatment: A comparison between patients switching from buprenorphine to methadone and maintenance treatment incident users (ANRS-Methaville trial)

Author: Caroline Lions, Perrine Roux, Laurent Michel, Bruno Spire, Sandra Nordmann, Marion Mora, Antoine Vilotitch, Alain Morel, Patrizia Carrieri, Gwenaëlle Maradan, 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), Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Oppelia, French National Agency for Research on Aids and Viral Hepatitis (ANRS), French Ministry of Health, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lissalde, Claire
Subjects: Adult, Male, medicine.medical_specialty, Poor responder, media_common.quotation_subject, Medicine (miscellaneous), Prison, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Opiate Substitution Treatment, medicine, Humans, 030212 general & internal medicine, Drug Trafficking, Psychiatry, Randomized Controlled Trials as Topic, media_common, Criminal behaviour, Opioid substitution treatment, business.industry, Health Policy, Public health, Longitudinal studies, 030227 psychiatry, 3. Good health, Buprenorphine, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Telephone interview, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Crime, France, Self Report, business, Self-reported offences, Methadone, medicine.drug
Abstract: International audience; Background: Patients receiving buprenorphine who are poor responders can continue to commit drug-related offences. Switching them from buprenorphine to methadone may result in reduced criminal behaviour. We compared self-reported offences and incarceration before and after starting methadone treatment of patients switching from buprenorphine (PSB) and maintenance treatment incident users (MIU). Methods: Data on offences, incarceration and other information, were obtained via a telephone interview. Mixed models were used to assess the impact of methadone initiation and being PSB or MIU on (1) the number of days when offences were committed (drug sale, drug purchase, other offences) and (2) experiencing incarceration during the previous 6 months. Results: Among the 176 patients with at least one assessment for self-reported offences, 51.7% were PSB. Receiving methadone was significantly associated with a reduction in the number of days when drug sale or drug purchase offences were committed, but not other offences. PSB and MIU groups were different only for drug purchase, as PSB were more likely to have a higher number of days of drug purchase from month 3 onwards. A reduction of 77% in the likelihood of experiencing incarceration was observed and this was comparable in PSB and MIU. Conclusion: Switching non-responding buprenorphine patients to methadone can result in a major reduction in offences and incarceration rates. Increasing access to methadone, using more flexible models of care is urgent for clinical and public health reasons. ã
Published: 2017
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45. Detectable HIV-RNA in semen of HIV controllers

Author: Faroudy Boufassa, Caroline Lascoux-combes, Olivier Lambotte, Claudine Duvivier, Nadia Mahjoub, Marie Laure Néré, Marianne Leruez-Ville, Jade Ghosn, Philippe Genet, Candice Meyzer, Marie Laure Chaix, Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), CHU Necker - Enfants Malades [AP-HP], Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Victor Dupouy, Centre d'infectiologie Necker-Pasteur [CHU Necker], 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), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Médecine interne-Immunologie clinique [Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Descartes - Paris 5 (UPD5), 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), This study was funded by a grant from the French National Agency for Research on AIDS and viral hepatitis (ANRS). The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript., 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), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ), 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)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institute for Emerging Diseases and Innovative Therapies (iMETI) ( IDMIT Center ), Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), and HAL UPMC, Gestionnaire
Subjects: 0301 basic medicine, Male, RNA viruses, Physiology, Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, medicine.disease_cause, Pathology and Laboratory Medicine, Polymerase Chain Reaction, law.invention, White Blood Cells, 0302 clinical medicine, Immunodeficiency Viruses, law, Animal Cells, MESH: Child, Blood plasma, Medicine and Health Sciences, Medicine, Public and Occupational Health, 030212 general & internal medicine, Young adult, lcsh:Science, Child, Polymerase chain reaction, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, MESH: Middle Aged, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: HIV Infections, Middle Aged, Vaccination and Immunization, 3. Good health, Body Fluids, Blood, Infectious Diseases, Medical Microbiology, MESH: Young Adult, Viral Pathogens, MESH: RNA, Viral, Cohort, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, HIV clinical manifestations, Anatomy, Pathogens, Cellular Types, Research Article, Adult, Adolescent, Immune Cells, 030106 microbiology, Plasma Cells, Immunology, Sexually Transmitted Diseases, Antiretroviral Therapy, Semen, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Peripheral blood mononuclear cell, Microbiology, Blood Plasma, Andrology, 03 medical and health sciences, Young Adult, Antiviral Therapy, Retroviruses, Humans, Sex organ, Microbial Pathogens, MESH: Semen, MESH: Adolescent, Blood Cells, MESH: Humans, business.industry, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, MESH: Adult, MESH: Polymerase Chain Reaction, Cell Biology, Virology, Diagnostic medicine, MESH: Male, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Preventive Medicine, business
Abstract: International audience; Background: Whether spontaneous low levels of HIV-1 RNA in blood plasma correlate with low levels of HIV-1 RNA in seminal plasma has never been investigated in HIV controller (HIC) men so far.Methods: HIC men enrolled in the ANRS CODEX cohort were eligible for the present study if they had no symptoms of sexually transmitted infections (STI). Two paired samples of blood and semen were collected four weeks apart. HIV-RNA was quantified in blood plasma (bpVL) and in seminal plasma (spVL), and cell-associated HIV-DNA was quantified in peripheral blood mononuclear cells (PBMC) and in non-sperm cells (NSC). Spearman rho tests were used to estimate correlations between bpVL and spVL.Results: Ten men were enrolled. At Day 0 (D0), spVL was detectable in four patients: 458; 552; 256 copies/mL and PCR signal detectable below limit of quantification (LoQ, 40 copies/mL). At Day 28 (D28), spVL was detectable in the same four participants in whom spVL was detectable at D0 with 582; 802; 752 and 50 copies/mL, respectively. HIV-DNA was detectable below LoQ in NSC of one patient at D0 visit. No patient had detectable HIV-DNA in NSC at D28 visit. At D0, bpVL and spVL were highly positively correlated (Spearman rho: 0.94; p = 0.0001). Similar results were found at D28.Conclusion: We show that HIV-RNA can be detected in the semen of HIC men, with levels positively correlated with those measured concomitantly in blood plasma. HIC men should be aware of the risk of HIV genital shedding, especially if viral blips are reported.
Published: 2017
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46. Characterization of the interaction between the HIV-1 Gag structural polyprotein and the cellular ribosomal protein L7 and its implication in viral nucleic acid remodeling

Author: Géraldine Laumond, Jean-Christophe Paillart, Yves Mély, Jean-Luc Darlix, Hala El Mekdad, Marina Elizabeth Biedma, Hugues de Rocquigny, Hassan Karnib, Eleonore Real, Kamal Kant Sharma, Marion Roy, Iuliia Malytska, Christiane Moog, Emmanuel Boutant, Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), This work was supported by SIDACTION, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), and Centre national de la recherche scientifique (CNRS)., de Rocquigny, Hugues, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: 0301 basic medicine, Models, Molecular, Biología, viruses, [SDV]Life Sciences [q-bio], RPL7, gag Gene Products, Human Immunodeficiency Virus, purl.org/becyt/ford/1 [https], chemistry.chemical_compound, Protein structure, Chaperone activity, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Translational regulation, GAG, Gag, CHAPERONE ACTIVITY, Zinc Fingers, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Dimerization, CIENCIAS NATURALES Y EXACTAS, Protein Binding, Ribosomal Proteins, Interaction, Otras Ciencias Biológicas, Biology, Ciencias Biológicas, 03 medical and health sciences, Nucleic acid thermodynamics, Ribosomal protein, Virology, Humans, purl.org/becyt/ford/1.6 [https], Nucleocapsid, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Messenger RNA, 030102 biochemistry & molecular biology, Research, Virus Assembly, NUCLEOCAPSID, RNA, HIV, Molecular biology, 030104 developmental biology, chemistry, Nucleic acid, HIV-1, INTERACTION, DNA, Molecular Chaperones
Abstract: Background: In HIV-1 infected cells, the integrated viral DNA is transcribed by the host cell machinery to generate the full length HIV-1 RNA (FL RNA) that serves as mRNA encoding for the Gag and GagPol precursors. Virion formation is orchestrated by Gag, and the current view is that a specific interaction between newly made Gag molecules and FL RNA initiates the process. This in turn would cause FL RNA dimerization by the NC domain of Gag (GagNC). However the RNA chaperoning activity of unprocessed Gag is low as compared to the mature NC protein. This prompted us to search for GagNC co-factors. Results: Here we report that RPL7, a major ribosomal protein involved in translation regulation, is a partner of Gag via its interaction with the NC domain. This interaction is mediated by the NC zinc fingers and the N- and C-termini of RPL7, respectively, but seems independent of RNA binding, Gag oligomerization and its interaction with the plasma membrane. Interestingly, RPL7 is shown for the first time to exhibit a potent DNA/RNA chaperone activity higher than that of Gag. In addition, Gag and RPL7 can function in concert to drive rapid nucleic acid hybridization. Conclusions: Our results show that GagNC interacts with the ribosomal protein RPL7 endowed with nucleic acid chaperone activity, favoring the notion that RPL7 could be a Gag helper chaperoning factor possibly contributing to the start of Gag assembly., Instituto de Estudios Inmunológicos y Fisiopatológicos
Published: 2016
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47. Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort]

Author: Philippe Morlat, Bruno Spire, François Dabis, Laurent Michel, Isabelle Poizot-Martin, Lang Jp, Marc-Arthur Loko, Bruno Marchou, Caroline Lions, Perrine Roux, Eric Rosenthal, Marc-Antoine Valantin, Lascoux-Combe C, Maria Winnock, Philippe Sogni, Didier Neau, M.-P. Carrieri, Dominique Salmon-Ceron, Karine Lacombe, Claudine Duvivier, Santé mentale et santé publique (SMSP - U1178), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Pierre Nicole [Paris], 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), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Laboratoire de Génétique Moléculaire [CHRU Strasbourg], CHRU Strasbourg, Service de Médecine Interne [CHU Nice] (Hôpital l'Archet), Hôpital l'Archet-Centre Hospitalier Universitaire de Nice (CHU de Nice), Pathologie Infectieuse et Tropicale, Clinique et Biologique [CHU Purpan de Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], 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), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service de Gastro-entérologie et hépatologie [AP-HP Hôpital Cochin], Sorbonne Paris Cité-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [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 Pasteur [Paris], Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, AbbVie and the French National Agency for Research on Aids and Viral Hepatitis (ANRS)., Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Lissalde, Claire
Subjects: Adult, Male, hepatitis C virus, medicine.medical_specialty, Adolescent, Substance-Related Disorders, Alcohol abuse, HIV Infections, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prevalence, medicine, Humans, Pharmacology (medical), drug/alcohol abuse, 030212 general & internal medicine, Psychiatry, Sida, Aged, Mini-international neuropsychiatric interview, biology, business.industry, Mental Disorders, Health Policy, virus diseases, HIV, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, biology.organism_classification, coinfection, 030227 psychiatry, 3. Good health, Substance abuse, Cross-Sectional Studies, Infectious Diseases, psychiatric disorders, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Coinfection, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Viral hepatitis, business, Cohort study
Abstract: Objectives The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. Methods The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). Results Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naive patients. Conclusions Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.
Published: 2016
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48. A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus-coinfected patients

Author: Ulveling, Damien, Le Clerc, Sigrid, Cobat, Aurélie, Labib, Taoufik, Noirel, Josselin, Laville, Vincent, Coulonges, Cédric, Carpentier, Wassila, Nalpas, Bertrand, Heim, Markus H., Poynard, Thierry, Cerny, Andreas, Pol, Stanislas, Bochud, Pierre-Yves, Dabis, Francois, Theodorou, Ioannis, Lévy, Yves, Salmon, Dominique, Abel, Laurent, Dominguez, Stéphanie, Zagury, Jean-François, Grp, HEPAVIH ANRS CO13 Cohort Study, Grp, Swiss Hepatitis C Cohort Study, Genoscan, French ANRS HC EP 26, Laboratoire génomique, bioinformatique et applications (GBA), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), 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), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospital Basel [Basel], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epatocentro Ticino, Université de Lausanne (UNIL), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Merck Sharp and Dohme (France), National Agency for Research on AIDS and Viral Hepatitis (ANRS), Swiss National Science Foundation [33CS30\₁48417, 324730-144054], Leenaards Foundation, Santos-Suarez Foundation, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire génomique, bioinformatique et applications ( GBA ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Human genetics of infectious diseases: Complex predisposition ( Equipe Inserm U1163 ), 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 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateforme Post-génomique de la Pitié-Salpêtrière ( P3S ), UMS omique ( OMIQUE ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Pitié-Salpêtrière [APHP], Université de Lausanne ( UNIL ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux Ségalen [Bordeaux 2], 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 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Université-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Université, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Cochin [AP-HP], The Rockefeller University [New-York], 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), and CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Liver Cirrhosis, medicine.medical_specialty, Linkage disequilibrium, MESH : Hepatitis C, Chronic, Hepatitis C virus, Genome-wide association study, HIV Infections, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, MESH: Genetic Loci, 03 medical and health sciences, Liver disease, Acquired immunodeficiency syndrome (AIDS), MESH : Genetic Loci, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, MESH : HIV Infections, Humans, MESH : Liver Cirrhosis, MESH: Humans, Hepatology, Coinfection, MESH: Polymorphism, Single Nucleotide, MESH : Humans, MESH : Polymorphism, Single Nucleotide, MESH : Disease Progression, MESH: HIV Infections, Hepatitis C, Chronic, medicine.disease, 3. Good health, MESH: Coinfection, MESH: Hepatitis C, Chronic, MESH : Coinfection, 030104 developmental biology, Genetic Loci, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Immunology, MESH: Genome-Wide Association Study, Disease Progression, MESH: Disease Progression, MESH: Liver Cirrhosis, Viral hepatitis, MESH : Genome-Wide Association Study, Genome-Wide Association Study
Abstract: International audience; There is growing evidence that human genetic variants contribute to liver fibrosis in subjects with hepatitis C virus (HCV) monoinfection, but this aspect has been little investigated in patients coinfected with HCV and human immunodeficiency virus (HIV). We performed the first genome-wide association study of liver fibrosis progression in patients coinfected with HCV and HIV, using the well-characterized French National Agency for Research on AIDS and Viral Hepatitis CO13 HEPAVIH cohort. Liver fibrosis was assessed by elastography (FibroScan), providing a quantitative fibrosis score. After quality control, a genome-wide association study was conducted on 289 Caucasian patients, for a total of 8,426,597 genotyped (Illumina Omni2.5 BeadChip) or reliably imputed single-nucleotide polymorphisms. Single-nucleotide polymorphisms with P values
Published: 2016
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49. What Level of Risk Compensation Would Offset the Preventive Effect of Early Antiretroviral Therapy? Simulations From the TEMPRANO Trial

Author: Kévin Jean, Marie-Claude Boily, Christine Danel, Raoul Moh, Anani Badjé, Annabel Desgrées-du-Loû, Serge Eholié, France Lert, Rosemary Dray-Spira, Xavier Anglaret, Eric Ouattara, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Imperial College London, Programme PAC-CI, ANRS France Recherche Nord & sud Sida-hiv hépatites, 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 Félix Houphouët-Boigny (UFHB), Laboratoire Population-Environnement-Développement (LPED), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), 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), 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), CHU Bordeaux [Bordeaux], This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis, Paris, France (grants TEMPRANO ANRS 12136 and TEMPRANO Social ANRS 12239)., HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université 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 Modélisation, épidémiologie et surveillance des risques pour la sécurité sanitaire ( MESuRS ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Pasteur-Cnam risques infectieux et émergents ( PACRI ), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), ANRS, 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 Félix Houphouët-Boigny ( UFHB ), Laboratoire Population-Environnement-Développement ( LPED ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Centre population et développement ( CEPED - UMR_D 196 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] ( CHU de Treichville ), 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 ), 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 ), and Jean, Kévin
Subjects: 0301 basic medicine, sub-Saharan Africa, HIV-1 INFECTION, sexual behaviors, IMPACT, Epidemiology, HIV Infections, law.invention, risk compensation, Condoms, 0302 clinical medicine, Randomized controlled trial, prevention, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, Public, Environmental & Occupational Health, SEXUAL-BEHAVIOR, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 11 Medical And Health Sciences, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Transmission (mechanics), Anti-Retroviral Agents, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Life Sciences & Biomedicine, Risk, medicine.medical_specialty, Sexual Behavior, antiretroviral therapy, COTE-DIVOIRE, Context (language use), 03 medical and health sciences, Risk-Taking, Condom, Disease Transmission, Infectious, Humans, METAANALYSIS, 01 Mathematical Sciences, Science & Technology, business.industry, HIV, 030112 virology, Confidence interval, Risk compensation, Sexual intercourse, Cote d'Ivoire, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, TRANSMISSION RISK, Multivariate Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, FOLLOW-UP, business, Demography
Abstract: International audience; Whether risk compensation could offset the preventive effect of early initiation of antiretroviral therapy (ART) on human immunodeficiency virus (HIV) transmission remains unknown. Using virological and behavioral data collected 12 months after inclusion in the TEMPRANO randomized trial of early ART (Abidjan, Côte d'Ivoire, 2009–2012), we estimated the risk of HIV transmission and compared it between the intervention (early ART; n = 490) and control (deferred ART; n = 467) groups. We then simulated increases in various sexual risk behaviors in the intervention group and estimated the resulting preventive effect. On the basis of reported values of sexual behaviors, we estimated that early ART had an 89% (95% confidence interval: 81, 95) preventive effect on the cumulative risk of HIV transmission over a 1-month period. This preventive effect remained significant for a wide range of parameter combinations and was offset (i.e., nonsignificant) only for dramatic increases in different sexual behaviors simulated simultaneously. For example, when considering a 2-fold increase in serodiscordance and the frequency of sexual intercourse together with a 33% decrease in condom use, the resulting preventive effect was 47% (95% confidence interval: −3, 74). An important reduction of HIV transmission may thus be expected from the scale-up of early ART, even in the context of behavioral change.
Published: 2016
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50. All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus–coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13–HEPAVIH Cohort

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