Descriptor: "MESH: Anti-HIV Agents" - Searchworks@Jio Institute Digital Library Search Results

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119 results on '"MESH: Anti-HIV Agents"'

1. Rate and Predictors of Ineffective HIV Protection in African Men Who Have Sex with Men Taking Pre-Exposure Prophylaxis

Author: Eubanks, August, Coulibaly, Bakary, Dembélé Keita, Bintou, Anoma, Camille, Dah, ter Tiero Elias, Mensah, Ephrem, Maradan, Gwenaëlle, Bourrelly, Michel, Mora, Marion, Riegel, Lucas, Rojas Castro, Daniela, Yaya, Issifou, Spire, Bruno, Laurent, Christian, Sagaon-Teyssier, Luis, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), ARCAD Santé PLUS [Bamako, Mali], Espace Confiance [Abidjan, Côte d’Ivoire], Association African Solidarité [Ouagadougou, Burkina Faso], Centre Muraz [Bobo-Dioulasso, Burkina Faso], Espoir Vie Togo [Lomé, Togo], Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and The COHMSM-PrEP Study Group.
Subjects: Male, Social Psychology, Anti-HIV Agents, [SDV]Life Sciences [q-bio], HIV Infections, Cohort Studies, MESH: Homosexuality, Male, Sexual and Gender Minorities, Community-based research, Burkina Faso, West Africa, Humans, MESH: Burkina Faso, Prospective Studies, MSM, Homosexuality, Male, MESH: Anti-HIV Agents, MESH: Cohort Studies, MESH: Humans, Public Health, Environmental and Occupational Health, HIV, MESH: HIV Infections, PrEP, MESH: Male, MESH: Prospective Studies, MESH: Sexual and Gender Minorities, Infectious Diseases, Pre-Exposure Prophylaxis, MESH: Pre-Exposure Prophylaxis
Abstract: We investigated the rate and predictors of ineffective HIV protection in men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) in a prospective cohort study from November 2017 to November 2020 in Mali, Côte d'Ivoire, Burkina Faso, and Togo. MSM had to be 18 years or older and at high risk of HIV infection to participate. They also received a comprehensive sexual health prevention package, including PrEP, in community-based clinics as part of the cohort study. Using socio-behavioral/clinical data, HIV protection during their most recent anal intercourse with a male partner was categorized as effective or ineffective (i.e., incorrect PrEP adherence and no condom use). Seventeen percent (500/2839) of intercourses were ineffectively protected for the 520 study participants. Predictors of ineffective HIV protection included being an event-driven user with financial difficulties, having a high alcohol misuse score, and not being a member of a community association. PrEP programs in West Africa must be tailored to socially vulnerable MSM who struggle to adopt PrEP.En este artículo hemos investigado la proporción y los factores predictivos de la protección ineficaz de VIH en un grupo de hombres, que tienen sexo con hombres (HSH) y que usan la profilaxis pre-exposición (PrEP). Se usaron los datos de un estudio de cohorte prospectivo realizado entre noviembre del 2017 y noviembre del 2020 en Mali, Costa de Marfil, Burkina Faso y Togo. Los participantes son HSH, de 18 años o más, y con alto riesgo de contaminación por el VIH. Estos han recibido un paquete completo de prevención en salud sexual incluyendo la PrEP en clínicas comunitarias como parte del estudio de cohorte. La protección contra el VIH durante la última relación sexual anal con un hombre fue categorizada como eficaz o ineficaz a partir de datos socio-comportamentales/clínicos (i.e. adhesión incorrecta à la PrEP y no utilización del condón). Concerniente a 520 participantes, 17% (500/2839) de las relaciones sexuales fueron protegidas de manera ineficaz. Entre los factores predictivos de la protección ineficaz contra el VIH se encuentran, el uso intermitente de la PrEP asociado a una situación financiera difícil, el consumo de alcohol y no ser miembro de una asociación comunitaria. Los programas de PrEP en África del Oeste, deben adaptarse a los HSH más vulnerables quienes podrían tener más dificultad para adoptar la PrEP.
Published: 2022

2. Loss to Follow-Up from HIV Pre-Exposure Prophylaxis Care in Men Who Have Sex with Men in West Africa

Author: August, Eubanks, Bakary, Coulibaly, Bintou Dembélé, Keita, Camille, Anoma, Ter Tiero Elias, Dah, Ephrem, Mensah, Gwenaëlle, Maradan, Michel, Bourrelly, Marion, Mora, Lucas, Riegel, Daniela, Rojas Castro, Issifou, Yaya, Bruno, Spire, Christian, Laurent, Luis, Sagaon-Teyssier, The CohMSM-PrEP Study Group, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), ARCAD Santé PLUS [Bamako, Mali], Espace Confiance [Abidjan, Côte d’Ivoire], Association African Solidarité [Ouagadougou, Burkina Faso], Espoir Vie Togo [Lomé, Togo], Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and The CohMSM-PrEP Study Group
Subjects: Male, Anti-HIV Agents, [SDV]Life Sciences [q-bio], HIV Infections, community-based research, MESH: Homosexuality, Male, Sexual and Gender Minorities, Virology, West Africa, Burkina Faso, key populations, Humans, MESH: Burkina Faso, MSM, Prospective Studies, MESH: Anti-HIV Agents, Homosexuality, Male, MESH: Humans, MESH: HIV Infections, MESH: Follow-Up Studies, PrEP, MESH: Male, MESH: Prospective Studies, MESH: Sexual and Gender Minorities, Infectious Diseases, HIV/AIDS, pre-exposure prophylaxis, Pre-Exposure Prophylaxis, MESH: Pre-Exposure Prophylaxis, Follow-Up Studies
Abstract: International audience; Loss to follow-up (LTFU) from HIV pre-exposure prophylaxis (PrEP) care compromises the goal of HIV elimination. We investigated the proportion of LTFU and associated risk factors among men who have sex with men (MSM) enrolled in a PrEP demonstration project in Burkina Faso, Côte d’Ivoire, Mali, and Togo. CohMSM-PrEP, a prospective cohort study, was conducted between November 2017 and June 2021 in community-based clinics. MSM aged 18 years or older at substantial risk of HIV infection received a comprehensive prevention package, including PrEP and peer education. LTFU was defined as not returning to the clinic for six months. Associated risk factors were investigated using a time-varying Cox’s model. Of 647 participants followed up for a median time of 15 months, 372 were LTFU (57.5%). LTFU was associated with younger age (adjusted hazard ratio [95% Confidence Interval]; 1.50 [1.17–1.94]), unemployment (1.33 [1.03–1.71]), depression (1.63 [1.12–2.38]), and perceiving no HIV risk with stable male partners (1.61 [1.23–2.10]). Contacting peer educators outside of scheduled visits was protective (0.74 [0.56–0.97]). Our findings show that LTFU from PrEP care in West African MSM is a major challenge to achieving HIV elimination, but that the involvement of peer educators in PrEP delivery helps to limit LTFU by providing users with adequate support.
Published: 2022

3. PrEP in the Context of Other HIV Risk Reduction Strategies Among Men Who Have Sex with Men: Results from the Flash! PrEP in Europe Survey

Author: Marion Di Ciaccio, Rosemary M. Delabre, Antoine Vilotitch, Giulio Maria Corbelli, Virginie Villes, Alejandro Ros Sánchez, Paul Zantkuijl, Holger Sweers, Flor Sanchez, Michael Meulbroek, Gus Cairns, Adeline Bernier, Jade Ghosn, Luìs Miguel Carvalho Rocha, Maria Luisa Cosmaro, Sascha Béla Duken, Monica Dan, Vincent Schlegel, Richard Stranz, Kai J. Jonas, Bruno Spire, Daniela Rojas Castro, Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Plus [Rome, Italy], Soa Aids Nederland [Amsterdam, The Netherlands], Deutsche AIDS-Hilfe E.V. [Berlin, Germany], Universidad Autónoma de Madrid (UAM), Projecte dels NOMS - Hispanosida, NAM [London, UK], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Grupo de Ativistas em Tratamentos [Lisbon, Portugal] (GAT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Fondazione LILA Milano [Milan, Italy] (FLM), University of Amsterdam [Amsterdam] (UvA), Romanian Association Against AIDS [Bucharest, Romania] (ARAS), AIDES [Pantin, France] (Mission Innovation Recherche Expérimentation), Maastricht University [Maastricht], Klinische Psychologie (Psychologie, FMG), RS: FPN WSP II, and Section Applied Social Psychology
Subjects: Male, MESH: Sexual Behavior, Anti-HIV Agents, Sexual Behavior, [SDV]Life Sciences [q-bio], HIV prevention, HIV Infections, BEHAVIORS, Condoms, MESH: Homosexuality, Male, Sexual and Gender Minorities, MESH: Condoms, Arts and Humanities (miscellaneous), Community-based research, PREVENTION TASP, Humans, MESH: Sexual Partners, MSM, Homosexuality, Male, MESH: Anti-HIV Agents, General Psychology, POSTEXPOSURE PROPHYLAXIS, MESH: Humans, MESH: HIV Infections, PrEP, MESH: Male, Europe, MESH: Sexual and Gender Minorities, GAY, Sexual Partners, ACCEPTABILITY, MESH: Risk Reduction Behavior, PATTERNS, Sexual orientation, MESH: Europe, Risk Reduction Behavior, PREEXPOSURE PROPHYLAXIS
Abstract: International audience; Combination HIV prevention covers a range of biomedical, behavioral, and socio-structural interventions. Despite the growing availability of pre-exposure prophylaxis (PrEP), it is not always accessible in European Centre for Disease Prevention and Control reporting countries and may not meet the needs of all at-risk populations. Based on the Flash! PrEP in Europe data, multiple correspondence analysis and hierarchical clustering were used to identify patterns in HIV prevention strategies among 9980 men who have sex with men (MSM). PrEP interest was evaluated among four identified clusters: (A) "high condom use, sometimes Treatment as Prevention (TasP)"; (B) "mix of methods, infrequent condom use"; (C) "high condom use, tendency to choose partners based on serological status" and (D) "moderate use of condoms mixed with other prevention strategies". Clusters B and D had higher PrEP interest. These results suggest that MSM use a range of behavioral and biomedical risk reduction strategies that are often combined. On-demand PrEP may meet the needs of MSM who infrequently use condoms and other prevention methods.
Published: 2022

4. Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting

Author: Caroline Lions, N Biezunski, Sophie Matheron, Romain Guery, Pierre-Marie Roger, Caroline Charlier, Mathieu Dupont, Line Meddeb, Philippe Van de Perre, V Joly, R Lecomte, Matthieu Revest, Claudine Duvivier, B Lefèvre, M Delestan, H Laurichesse, H Marty, F Lemaitre, Martine Valette, Marc-Antoine Valantin, A S Ritleng, A Ménard, Eric Cua, M. Alvarez, A Raoux, M P Bouillon, A Sève, A Brebion, Claire Triffault-Fillit, Sylvie Bregigeon, M Carles, O. Aubry, S Hénard, P. Dellamonica, A Charmillon, E Alidjinou, V Brodard, M Tetart, F Raffi, Paul-Henri Consigny, O Lesens, C Brunet-Cartier, I Lamaury, S Giaché, Amandine Gagneux-Brunon, Jacques Reynes, Karine Sauné, Clotilde Allavena, Q Lepiller, Véronique Reliquet, C Louisin, I Perbost, Jean-Luc Berger, B Prouvost-Keller, Eric Delaporte, Isabelle Lamaury, C Gubavu, L Fagour, Laurent Cotte, G Gaube, Elina Teicher, Faouzi Souala, C Blanc, Dominique Merrien, Isabelle Poizot-Martin, C Drobacheff-Thiébaut, T May, P Richard, M A Trabaud, M Bistoquet, C Klotz, Samira Fafi-Kremer, M Marcel, Charlotte Charpentier, L Lelièvre, K Risso, Sandrine Pierre-François, S Ferrando, S Breaud, S Bevilacqua, A Montoya Ferrer, T Rojas-Rojas, D Boucher, Yazdan Yazdanpanah, Olivier Lortholary, Philippe Colson, Anne-Sophie Brunel, F-Xavier Lescure, Christelle Tomei, M Martin-Degioanni, Eric Rosenthal, Philippe Bossi, Patrick Miailhes, Kevin Bouiller, Lise Cuzin, A Foltzer, F Boulard, Michel Vidal, V Mondain, H Colson, J Pasquier, I Kmiec, F Alby-Laurent, R Agher, A Cabié, Guillaume Martin-Blondel, L Hocqueloux, M Colin, A Madrid, Faiza Ajana, J M Livrozet, V Rio, Karima Amazzough, C Merle de Boever, M Digumber, Thomas Perpoint, A Cheret, Laurence Bocket, Z Julia, Virginie Ferré, M Pradier, M Poisson-Vannier, A Legoff, M J Soavi, Y Quertainmont, Marine Morrier, Christian Chidiac, F Touam, O Zaegel-Faucher, A Marquise, G Benabdelmoumen, Florence Ader, T Guimard, M C Receveur, J C Tardy, P Morineau, K Guitteaud, D. Rey, S Leautez, Catherine Chirouze, Benoit Tressières, A. Ivanova, C Charre, J Reynes, Christian Pradier, Catherine Dhiver, Laurent Boyer, E Frentiu, David Rey, C Allavena, Anne Motte, Tristan Ferry, C Pronier, M. Hentzien, C Rouzaud, O Cabras, K Jidar, F Najioullah, C Clavel, M Orticoni, S Patrat-Delon, M Cavellec, Cécile Herrmann-Storck, V Baclet, Jade Ghosn, M Perry, S Wehrlen-Pugliese, J. M. Chapplain, R Palich, Laurent Hocqueloux, A Maillard, C Deschanvres, O Deradji, F. Lucht, A Grégoire, Veronique Joly, R Ouissa, C Daniel, N Mrozek, D Chirio, O Bollangier, J Bavay, P. Le Turnier, A Maka, C Rioux, Colin Deschanvres, C Brochier, Elisabeth Botelho-Nevers, A Meybeck, C Ceppi, J Lourenco, François Bénézit, Thomas Jovelin, G Zouzou, N Tissot, N. Viget, F Brunel-Dalmas, Brigitte Montes, N Chellum Rungen, K Rome, David Boutoille, B Bigeard, I Fabre, N Oran, M Lefebvre, P Point, C Etienne, Diane Descamps, G Thomas, S Le Gac, Cyrille Delpierre, Pierre Tattevin, M Godinot, P Fischer, C Aumeran, C Boulard, Elisabeth André-Garnier, J Sinteff, V Ronat, F Goehringer, Romain Palich, Luminita Schneider, I Touitou, Eric Billaud, P Thill, Catherine Varache, Olivier Robineau, I Jaquet, Roland Landman, Cédric Arvieux, B. Bonnet, V Rzepecki, Olivier Grossi, Christian Rabaud, L Laine, F Louni, C Cheneau, S Markowicz, Hélène Laroche, A Gervais, C Bernard-Henry, E Goncalvez, N Lerolle, M André, D Lambert, André Boibieux, L. Porte, S Bouchez, E Paredes, E Aïssi, V. Le Moing, S Degroodt, Sylvie Abel, André Cabié, B Lafon-Desmurs, O Babre, M Baldeyrou, C Debreux, A Rodallec, Pierre Delobel, V Icard, Agathe Becker, Edouard Tuaillon, Hervé Tissot-Dupont, M Mokhtari, C Morlat, I Alcaraz, Anne Frésard, O Cannesson, Elodie Curlier, P Chiarello, S. Roux, F Bani-Sadr, François Raffi, Florent Valour, M Piffaut, M Priester, A. Belkhir, J Romaru, Cécile Goujard, A Castro, G Cessot, A Mirand, C Pouderoux, A Brunet, C Michelangeli, Y N’guyen, Patrice Muret, Elisa Demonchy, Christine Jacomet, D Makhloufi, E Jeanmaire, Marialuisa Partisani, Véronique Obry-Roguet, J Turmel, C Mélounou, J. Durant, Christine Katlama, P Parize, O Robineau, S Seang, F. Bozon, S Galie, Alexa Debard, E de Mautort, C Duvivier, Fanny Lanternier, Alain Makinson, A Barrail-Tran, C Aguilar, A Naqvi, Rodolphe Garraffo, N Meftah, C Biron, A de Monte, Pascal Pugliese, V Corbin, S Jaureguiberry, E Lafont, L Hustache Mathieu, R Colarino, Isabelle Ravaux, C Henquell, Benoit Pilmis, M Grégoire, P Lansalot, E Ressiot, T. Huleux, Olivier Baud, S Sécher, R Dupin de Majoubert, J Leporrier, L Cuzin, E Chevalier, M Poinot, R Tubiana, S Lariven, A Boucher, N Atoui, Firouzé Bani-Sadr, T Prazuck, M Ducassou, Gilles Peytavin, A Soria, B J Gaborit, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Dat’AIDS Study Group, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Gustave Dron [Tourcoing], Institut Pasteur [Paris] (IP), Centre Hospitalier Régional d'Orléans (CHRO), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de la Martinique [Fort de France], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Clermont-Ferrand, and Université Clermont Auvergne (UCA)
Subjects: Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Pyridones, MESH: Piperazines, HIV Infections, Emtricitabine, Piperazines, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, MESH: Pyridones, Oxazines, MESH: Emtricitabine, Humans, Medicine, Pharmacology (medical), MESH: Anti-HIV Agents, Pharmacology, MESH: Heterocyclic Compounds, 3-Ring, MESH: Humans, business.industry, Rilpivirine, Lamivudine, MESH: HIV Infections, Viral Load, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Virological failure, Regimen, Infectious Diseases, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Dolutegravir, Cohort, MESH: Rilpivirine, business, MESH: Viral Load, Heterocyclic Compounds, 3-Ring, MESH: Oxazines, medicine.drug, MESH: Lamivudine
Abstract: Background Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. Objectives We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Methods Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. Results We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC. Conclusions In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.
Published: 2022

5. Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study

Author: Jean-Michel Molina, Jade Ghosn, Lambert Assoumou, Constance Delaugerre, Michèle Algarte-Genin, Gilles Pialoux, Christine Katlama, Laurence Slama, Geoffroy Liegeon, Lydie Beniguel, Michel Ohayon, Hanane Mouhim, Lauriane Goldwirt, Bruno Spire, Bénédicte Loze, Laure Surgers, Juliette Pavie, Jérémy Lourenco, Mohamed Ben-Mechlia, Soizic Le Mestre, Daniela Rojas-Castro, Dominique Costagliola, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Hôtel-Dieu, 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), CHU Saint-Antoine [AP-HP], 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)-Université Paris Cité (UPCité), ANRS France Recherche Nord & sud Sida-hiv hépatites, and AIDES [Pantin, France]
Subjects: Adult, Male, Adolescent, Epidemiology, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Immunology, HIV Infections, Medication Adherence, MESH: HIV-1, MESH: Homosexuality, Male, Sexual and Gender Minorities, MESH: Tenofovir, Virology, MESH: Emtricitabine, Emtricitabine, Humans, Prospective Studies, MESH: Anti-HIV Agents, Homosexuality, Male, Tenofovir, MESH: Adolescent, MESH: Humans, MESH: Adult, MESH: HIV Infections, MESH: Medication Adherence, MESH: Prospective Studies, MESH: Male, MESH: Sexual and Gender Minorities, Infectious Diseases, HIV-1, Female, Pre-Exposure Prophylaxis, MESH: Female, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; BackgroundThere are few data available regarding the use of on-demand pre-exposure prophylaxis (PrEP) for HIV prevention. We aimed to assess PrEP effectiveness, adherence, and safety in adults using daily or on-demand PrEP.MethodsWe conducted a prospective observational cohort study (ANRS PREVENIR) at 26 sites in the Paris region, France. We enrolled HIV-negative adults (aged ≥18 years) at high risk of HIV infection who were starting or continuing PrEP. PrEP was prescribed as a fixed-dose combination of tenofovir disoproxil and emtricitabine (245 mg and 200 mg, respectively, per pill). PrEP could be prescribed as a daily regimen with one pill per day or, in men who have sex with men (MSM) or in transgender women who have sex with men, as an on-demand regimen following the IPERGAY dosing recommendation. At enrolment and every 3 months thereafter, participants were tested for HIV and provided information regarding the PrEP dosing regimen used. Adherence to PrEP was assessed by self-report and by tenofovir diphosphate concentrations in dried blood spots. The primary outcome of HIV-1 incidence was assessed using Poisson regression among participants who started PrEP. This study is registered with ClinicalTrials.gov, NCT03113123, and EudraCT, 2016A0157744.FindingsBetween May 3, 2017, and May 2, 2019, 3082 people were assessed for eligibility and 3065 participants were enrolled. 3056 (99·7%) of 3065 participants reported using PrEP and were included in the analyses. The median age was 36 years (IQR 29–43), 1344 (44·0%) of 3056 participants were PrEP-naive, and 3016 (98·7%) were MSM. At enrolment, 1540 (50·5%) of 3049 participants opted for daily PrEP dosing and 1509 (49·5%) opted for on-demand PrEP dosing; these proportions remained stable during follow-up. Median follow-up was 22·1 months (IQR 15·9–29·7) and incidence of study discontinuation was 17·6 participants (95% CI 16·5–18·7) per 100 person-years. At the data cutoff on Sept 30, 2020, there had been six HIV-1 seroconversions (three participants using daily PrEP and three using on-demand PrEP; all were MSM) over 5623 person-years. Overall HIV-1 incidence was 1·1 cases (95% CI 0·4–2·3) per 1000 person-years, and did not differ between participants using daily PrEP and those using on-demand PrEP (incidence rate ratio 1·00, 95% CI 0·13–7·49; p=0·99). Four participants (two using daily PrEP and two using on-demand PrEP) discontinued PrEP due to treatment-related adverse events (nausea [n=2], vomiting and diarrhoea [n=1], and lumbar pain [n=1]).InterpretationIn this study, which enrolled mainly MSM, HIV-1 incidence on PrEP was low and did not differ between participants using daily PrEP and those using on-demand PrEP. On-demand PrEP therefore represents a valid alternative to daily PrEP for MSM, providing greater choice in HIV prevention.FundingANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France.TranslationFor the French translation of the abstract see Supplementary Materials section.; ANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France.
Published: 2021

6. Changes in Sexual Behaviors in Men Who Have Sex with Men: A Comparison Between the Double-Blind and Open-Label Extension Phases of the ANRS-IPERGAY Trial

Author: Cécile Tremblay, Marie Suzan-Monti, Christian Chidiac, Jean-Michel Molina, Daniela Rojas Castro, Christel Protière, Mohamed Mimi, Laurence Meyer, Bruno Spire, Marion Di Ciaccio, Catherine Capitant, Luis Sagaon-Teyssier, Marie Préau, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Pantin, France], Coalition Internationale Sida [Pantin, France] (Programme Recherche Communautaire), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), 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 [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), ANRS IPERGAY Study Group: J-M Molina, C Capitant, B Spire, G Pialoux, L Cotte, I Charreau, C Tremblay, J-M Le Gall, E Cua, A Pasquet, F Raffi, C Pintado, C Chidiac, J Chas, P Charbonneau, C Delaugerre, M Suzan-Monti, B Loze, J Fonsart, G Peytavin, A Cheret, J Timsit, G Girard, N Lorente, M Préau, J F Rooney, M A Wainberg, D Thompson, W Rozenbaum, V Doré, L Marchand, M-C Simon, N Etien, J-P Aboulker, L Meyer, J-F Delfraissy, C Pintado, B Loze, C Delaugerre, P Charbonneau, C Gatey, D Ponscarme, P Penot, L Niedbalski, R Veron, J Delgado, E Dalle, S Parlier, I Madelaine, J Fonsart, M Danet, N Mahjoub, N Mezreb, K Moudachirou, S Morel, G Conort, F Lorho, M Meunier, W Rozenbaum, J M Molina, J Chas, C Monfort, J Foucoin, B Boissavy, S Cousseau, S Huon, M Danet, A Djessima, V Berrebi, A Adda, S le Nagat, L Zarka, J Berdougo, G Pialoux, C Chidiac, N Mzoughi, F Clement, A Decouty, C Chapolard, M Godinot, C Adouard-Groslafeige, J Koffi, A Pansu, A Becker, S Pailhes, F Bonnet, F Jeanblanc, C Brochier, X Teruin, S Rouby, L Gilly, L Cotte, C Beauvais, P Arlotto, C Fortin, A Talbot, A Chamberland, A McKenzie, M Blanchette, R Rousseau, K Montheuth, D Thompson, M Morin, M Wainberg, C Tremblay, C Etienne, F Tolonin, S Breaud, V Péchenot, S Bagge, T Cepitelli, P M Roger, E Rosenthal, E Cua, A Cheret, P Cornavin, S Vandamme, J Lambec, N Dumon, O Leclanche, T Huleux, R Biekre, O Robineau, H Melliez, H Bazus, A Pasquet, C Bernaud, M Besnier, B Bonnet, N Hall, M Cavellec, H Hue, L Larmet, M Colas, R Choquet, F Raffi, Dupuis, Christine, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Safe Sex, MESH: Sexual Behavior, [SDV]Life Sciences [q-bio], HIV Infections, Gee, law.invention, Men who have sex with men, 0302 clinical medicine, law, Medicine, MESH: Sexual Partners, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Anti-HIV Agents, Generalized estimating equation, MESH: Middle Aged, MESH: HIV Infections, Middle Aged, PrEP, 3. Good health, [SDV] Life Sciences [q-bio], Sexual Partners, Infectious Diseases, Sexual behavior, MESH: Risk-Taking, MESH: Young Adult, MESH: Risk Reduction Behavior, France, Open label, 0305 other medical science, Adult, Canada, Social Psychology, Anti-HIV Agents, ANRS-IPERGAY trial, Sexual Behavior, MESH: Safe Sex, Double blind, MESH: Homosexuality, Male, Young Adult, 03 medical and health sciences, Risk-Taking, Double-Blind Method, Condom, MESH: Canada, Humans, MSM, Homosexuality, Male, 030505 public health, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, HIV risk management, MESH: Adult, Odds ratio, MESH: Male, MESH: France, Behaviors, Pre-Exposure Prophylaxis, business, Risk Reduction Behavior, Demography, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; Pre-Exposure Prophylaxis (PrEP) is changing the landscape of HIV prevention, and may bring changes in sexual behaviors. The double-blind phase (DBP) and open-label extension (OLE) study of the ANRS-IPERGAY trial allowed us to assess changes in sexual behavior of men who have sex with men (MSM) taking sexual activity-based (i.e., on-demand) PrEP. Generalized Estimating Equation (GEE) models found a significant decrease in the number of sexual partners (Coefficient [CI95%], p value; - 0.37[- 0.70 to - 0.04], p = 0.03) between the DBP and OLE as well as in the number of sexual relations (- 0.25 [- 0.49 to 0.00], 0.04). GEE estimates also showed that respondents' most recent sexual relation was less likely to have been with an unknown casual partner during the OLE than during the DBP (Odds Ratio [CI95%], p value: 0.75[0.62-0.92], 0.005). Furthermore, they showed an increase in the proportion of condomless anal sex in the OLE (1.32[1.04-1.67], 0.02), a decrease in the proportion of 'suboptimal PrEP adherence' over time (0.75[0.58-0.97], p = 0.03), a decrease in PrEP only use (0.73[0.55-0.96], 0.03) and in both PrEP and condom use over time (0.70[0.51-0.95], 0.02) and finally, a decrease in alcohol consumption between the DBP and OLE (0.74[0.61-0.90], 0.002). We observed both protective and risky behaviors in terms of HIV and STI risk after on-demand PrEP uptake in the OLE phase. Our findings are consistent with results from previous PrEP trials.
Published: 2020

7. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon

Author: Alexandra Calmy, Tamara Tovar Sanchez, Charles Kouanfack, Mireille Mpoudi-Etame, Sandrine Leroy, Ségolène Perrineau, Martial Lantche Wandji, Darius Tetsa Tata, Pierette Omgba Bassega, Thérèse Abong Bwenda, Marie Varloteaux, Marcel Tongo, Eitel Mpoudi-Ngolé, Alice Montoyo, Noémie Mercier, Vincent LeMoing, Martine Peeters, Jacques Reynes, Eric Delaporte, A Calmy, T Tovar Sanchez, C Kouanfack, M Mpoudi-Etame, S Leroy, S Perrineau, M Lantche-Wandji, D Tetsa-Tata, P Omgba-Bassega, T Abong-Bwenda, M Varloteaux, M Tongo, E Mpoudi-Ngolé, A Montoyo, N Mercier, V LeMoing, M Peeters, J Reynes, E Delaporte, A Ayouba, A Agholeng, C Butel, A Cournil, S Eymard-Duvernay, B Granouillac, S Izard, A Lacroix, L Serrano, N Vidal, PJ Fouda, R Mougnoutou, J Olinga, V Omgba, SC Tchokonte-Ngandé, B Ymele, CD Epoupa-Mpacko, M Fotso, R Moukoko, T Nké, A Akamba, S Lekelem, SB Tongo-Fotack, S Ngono, M Tanga, E Ebong, G Edoul-Mbesse, L Ciaffi, S Koulla-Shiro, G Manirakiza, ED Mimbé, S Boyer, M Bousmah, G Maradan, ML Nishimwe, B Spire, MP Lê, G Peytavin, A Diallo, I Fournier, C Rekacewicz, C Perez Casas, Hôpitaux Universitaires de Genève (HUG), 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), Université de Dschang, Hôpital Central de Yaoundé [Yaoundé], Hôpital Militaire de Yaoundé, Partenaires INRAE, Hôpital de la Cité Verte [Yaoundé], Institut de Recherches Médicales et d'Etudes des Plantes Médicinales (IMPM), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Cyclopropanes, 0301 basic medicine, MESH: CD4 Lymphocyte Count, Epidemiology, MESH: Piperazines, HIV Infections, Piperazines, MESH: Antiretroviral Therapy, Highly Active, law.invention, MESH: HIV-1, chemistry.chemical_compound, 0302 clinical medicine, MESH: Cyclopropanes, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Clinical endpoint, MESH: Duration of Therapy, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Treatment Outcome, MESH: Middle Aged, Lamivudine, virus diseases, MESH: HIV Infections, Middle Aged, Viral Load, 3. Good health, Treatment Outcome, Infectious Diseases, MESH: Young Adult, Alkynes, MESH: Benzoxazines, Dolutegravir, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Viral Load, Heterocyclic Compounds, 3-Ring, Viral load, medicine.drug, Adult, medicine.medical_specialty, Efavirenz, Anti-HIV Agents, Pyridones, Immunology, Young Adult, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Virology, Internal medicine, MESH: Pyridones, Oxazines, medicine, Humans, MESH: Heterocyclic Compounds, 3-Ring, Duration of Therapy, MESH: Humans, business.industry, MESH: Adult, medicine.disease, 030112 virology, Benzoxazines, CD4 Lymphocyte Count, Regimen, chemistry, HIV-1, business, MESH: Alkynes, MESH: Oxazines, MESH: Female
Abstract: International audience; Background: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96.Methods: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing.Findings: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p
Published: 2020

8. Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study-authors' response

Author: Christine Katlama, Lambert Assoumou, Marc-Antoine Valantin, Cathia Soulié, Esteban Martinez, Lydie Béniguel, Olivier Bouchaud, François Raffi, Jean-Michel Molina, Soraya Fellahi, Gilles Peytavin, Anne-Geneviève Marcelin, Sami Kolta, Jacqueline Capeau, Severine Gibowski, Fanny Cardon, Jacques Reynes, Dominique Costagliola, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de virologie [CHU Pitié-Salpêtrière], Hospital Clinic [Barcelona, Spain], Universitat de Barcelona (UB), Service de maladies infectieuses et tropicales [CHU Avicenne], 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), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], ANRS France Recherche Nord & sud Sida-hiv hépatites, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Montpellier 1 (UM1)-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)
Subjects: Microbiology (medical), MESH: Raltegravir Potassium, Anti-HIV Agents, HIV Infections, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Pyridazines, Raltegravir Potassium, Nitriles, Humans, Pharmacology (medical), 030212 general & internal medicine, MESH: Anti-HIV Agents, ComputingMilieux_MISCELLANEOUS, Pharmacology, 0303 health sciences, MESH: Humans, 030306 microbiology, MESH: HIV Infections, MESH: Nitriles, 3. Good health, Pyridazines, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pyrimidines, MESH: Pyrimidines, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Abstract: International audience
Published: 2020

9. Are PrEP services in France reaching all those exposed to HIV who want to take PrEP? MSM respondents who are eligible but not using PrEP (EMIS 2017)

Author: Stéphane Morel, Annie Velter, David Michels, Virginie Villes, Rosemary M. Delabre, Margot Annequin, Tristan Alain, Axel J. Schmidt, Daniela Rojas Castro, Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), AIDES [Pantin, France], London School of Hygiene and Tropical Medicine (LSHTM), Santé publique France - French National Public Health Agency [Saint-Maurice, France], 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), and Dupuis, Christine
Subjects: Male, Health Knowledge, Attitudes, Practice, MESH: Sexual Behavior, Health (social science), pre-exposure prophylaxis (PrEP), [SDV]Life Sciences [q-bio], MESH: Health Knowledge, Attitudes, Practice, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Health Services Accessibility, Condoms, Health insurance system, 0302 clinical medicine, Surveys and Questionnaires, Medicine, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Health Services Accessibility, MESH: Patient Acceptance of Health Care, MESH: HIV Infections, 3. Good health, [SDV] Life Sciences [q-bio], PrEP delivery, France, 0305 other medical science, Adult, medicine.medical_specialty, Social Psychology, Anti-HIV Agents, Sexual Behavior, PrEP access, PrEP eligibility, MESH: Homosexuality, Male, 03 medical and health sciences, MESH: Condoms, MESH: Cross-Sectional Studies, Humans, MSM, Homosexuality, Male, MESH: Surveys and Questionnaires, 030505 public health, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, Patient Acceptance of Health Care, MESH: Male, MESH: France, Cross-Sectional Studies, Family medicine, Pre-Exposure Prophylaxis, business, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; Pre-exposure prophylaxis (PrEP) is fully reimbursed by the French health insurance system since 2016. However, uptake of PrEP is slower than expected and little is known about men who have sex with men (MSM) who are eligible for PrEP according to French guidelines, but not using it. This study aims to (1) assess and describe MSM that are eligible to PrEP but not using it, and (2) identify potential individual and structural barriers of PrEP uptake among eligible MSM who are aware and intend to take PrEP. Data from EMIS-2017, a cross-sectional internet survey among gay, bisexual, and other MSM, were used. Among 7965 respondents without diagnosed HIV, 9.2% were PrEP users. Among 7231 non-PrEP users, 35.2% were eligible to PrEP and 15.2% were eligible, aware and intended to take PrEP. Eligible MSM who are not using PrEP are mostly younger, students, less "out", living in small cities, using condoms more frequently but still with low self-efficacy regarding safe sex and more distant from preventive health care and information than PrEP users. Despite free PrEP availability in France, results suggest that PrEP is not fully accessible and that there is a need to increase PrEP demand and decentralize PrEP delivery.
Published: 2020

10. HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort)

Author: Perrine Roux, Camelia Protopopescu, Issifou Yaya, Dominique Salmon-Ceron, Lionel Piroth, Eric Rosenthal, Wildo Navegantes de Araújo, Fabienne Marcellin, Melina Erica Santos, Philippe Sogni, Philippe Morlat, Laure Esterle, Maria Patrizia Carrieri, François Bailly, Linda Wittkop, Universidade de Brasilia [Brasília] (UnB), 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), 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), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-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], Hôpital l'Archet, Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), 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), 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 Vittecoq, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, S Dominguez, 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, D Salmon, R Usubillaga, P Sogni, B Terris, P Tremeaux, C Katlama, H Stitou, Y Benhamou, F Charlotte, S Fourati, A Simon, P Cacoub, S Nafissa, I Poizot-Martin, O Zaegel, H Laroche, C Tamalet, G Pialoux, J Chas, P Callard, F Bendjaballah, C Le Pendeven, B Marchou, L Alric, S Metivier, J Selves, F Larroquette, E Rosenthal, A Naqvi, V Rio, J Haudebourg, M C Saint-Paul, C Partouche, O Bouchaud, M Ziol, Y Baazia, M Uzan, D Garipuy, M J Ferro-Collados, F Nicot, Y Yazdanpanah, H Adle-Biassette, G Alexandre, C Lascoux-Combe, 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, C Goujard, Y Quertainmont, E Teicher, C Pallier, D Vittecoq, O Lortholary, C Rouzaud, J Lourenco, F Touam, C Louisin, V Avettand-Fenoel, A Mélard, D Neau, A Ochoa, E Blanchard, S Castet-Lafarie, C Cazanave, D Malvy, M Dupon, H Dutronc, F Dauchy, L Lacaze-Buzy, P Bioulac-Sage, S Reigadas, P Morlat, D Lacoste, F Bonnet, N Bernard, M Hessamfar, F Paccalin, C Martell, M C Pertusa, M Vandenhende, P Merciéer, T Pistone, M C Receveur, M Méchain, P Duffau, C Rivoisy, I Faure, S Caldato, J L Pellegrin, J F Viallard, E Lazzaro, C Greib, D Zucman, C Majerholc, E Farfour, F Boué, J Polo Devoto, I Kansau, V Chambrin, C Pignon, L Berroukeche, R Fior, V Martinez, C Deback, Y Lévy, J D Lelièvre, A S Lascaux, G Melica, E Billaud, F Raffi, C Allavena, V Reliquet, D Boutoille, C Biron, A Rodallec, L Le Guen, 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, 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, H Aumaître, F Bani-Sadr, D Lambert, Y Nguyen, J L Berger, D Rey, M Partisani, M L Batard, C Cheneau, M Priester, C Bernard-Henry, E de Mautort, P Gantner, S Fafi-Kremer, G Peytavin, F Roustant, I Kmiec, L Traore, S Lepuil, S Parlier, V Sicart-Payssan, E Bedel, 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, E Boerg, 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, S Tezkratt, I Yaya, T Barré, T Rojas Rojas, V Villes, M Baudoin, M Santos, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université de Toulon (UTLN)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and Dupuis, Christine
Subjects: Male, Marijuana Abuse, [SDV]Life Sciences [q-bio], HIV Infections, Hepacivirus, Substance use, medicine.disease_cause, Coffee, MESH: Antiretroviral Therapy, Highly Active, Cohort Studies, MESH: Proportional Hazards Models, MESH: HIV-1, 0302 clinical medicine, Alcohol and weight, Antiretroviral Therapy, Highly Active, MORPH3Eus, MESH: Obesity, MESH: Hepacivirus, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Cohort Studies, MESH: Middle Aged, biology, Coinfection, Confounding, virus diseases, Hepatitis C, MESH: HIV Infections, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Cohort, Female, France, 0305 other medical science, Adult, medicine.medical_specialty, Social Psychology, Anti-HIV Agents, Hepatitis C virus, MESH: Marijuana Abuse, Binge drinking, Marijuana Smoking, 03 medical and health sciences, Thinness, Internal medicine, medicine, Humans, Obesity, Mortality, Proportional Hazards Models, MESH: Hepatitis C, Behavior, 030505 public health, MESH: Thinness, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, HIV, MESH: Coffee, MESH: Marijuana Smoking, MESH: Adult, biology.organism_classification, medicine.disease, MESH: Male, MESH: Coinfection, MESH: France, HIV-1, Cannabis, business, MESH: Female
Abstract: International audience; Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.
Published: 2020

11. Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery

Author: Patumrat Sripan, Saik Urien, Billy Amzal, Thitiporn Siriwachirachai, P. Kanjanavikai, Gonzague Jourdain, P. Sabsanong, Suporn Koetsawang, Tim R. Cressey, Sophie Le Coeur, Marc Lallemant, Tapnarong Jarupanich, Boonsong Rawangban, Virat Klinbuayaem, Nicole Ngo-Giang-Huong, Phpt site investigators, Phaiboon Wanasiri, Drugs for Neglected Diseases Initiative, Certara, Institut de Recherche pour le Développement (IRD), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University [Cambridge]-Chiang Mai University (CMU), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and Institut national d'études démographiques (INED)
Subjects: prevention of mother-to-child transmission, HIV Infections, 030312 virology, [SHS]Humanities and Social Sciences, MESH: Pregnancy, Pregnancy, Pharmacology (medical), Young adult, MESH: Anti-HIV Agents, MESH: Nevirapine, Pregnancy Complications, Infectious, 0303 health sciences, Transmission (medicine), Obstetrics, MESH: Infant, Newborn, virus diseases, MESH: Zidovudine, clinical trial, Lopinavir, MESH: HIV Infections, Viral Load, Thailand, historical control, MESH: Mothers, 3. Good health, MESH: Infectious Disease Transmission, Vertical, Drug Combinations, Infectious Diseases, MESH: Young Adult, Lamivudine, Female, MESH: Viral Load, Viral load, Zidovudine, medicine.drug, MESH: Lamivudine, Adult, medicine.medical_specialty, Nevirapine, Anti-HIV Agents, MESH: Bayes Theorem, antiretroviral therapy, education, Mothers, Bayesian design, Article, 03 medical and health sciences, Young Adult, medicine, Humans, intrapartum transmission, MESH: Pregnancy Complications, Infectious, MESH: Thailand, MESH: Drug Combinations, MESH: Humans, business.industry, Infant, Newborn, HIV, MESH: Adult, Bayes Theorem, medicine.disease, Infectious Disease Transmission, Vertical, meta-analysis, Regimen, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: Infants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk. Methods: In this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infant zidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated
Published: 2020

12. Associations between methamphetamine use and lack of viral suppression among a cohort of HIV-positive persons who inject drugs in Hai Phong, Vietnam

Author: Roselyne Vallo, Kamyar Arasteh, Delphine Rapoud, Sao M. Le, Don C. Des Jarlais, Didier Laureillard, Laurent Michel, Hoang T. Giang, Duong Thi Huong, Catherine Quillet, Nicolas Nagot, Jonathan Feelemyer, Vu Hai Vinh, Nham Thi Tuyet Thanh, Khuat Thi Hai Oanh, Pham Minh Khue, Jean-Pierre Molès, Herrada, Anthony, College of Global Public Health [New York], New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Haiphong University of Medicine and Pharmacy, Supporting Community Development Initiatives [Hanoï, Vietnam], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Viet Tiep Hospital [Hai Phong, Vietnam], Centre Pierre Nicole [Paris], 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 Hospitalier Universitaire de Nîmes (CHU Nîmes), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, 0301 basic medicine, people who inject drugs, HIV Infections, MESH: Antiretroviral Therapy, Highly Active, Methamphetamine, Cohort Studies, Drug Users, methadone, MESH: Treatment Adherence and Compliance, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Immunology and Allergy, Medicine, 030212 general & internal medicine, Viral suppression, MESH: Anti-HIV Agents, Substance Abuse, Intravenous, MESH: Cohort Studies, media_common, MESH: Treatment Outcome, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Middle Aged, MESH: HIV Infections, Middle Aged, Viral Load, Random effects model, 3. Good health, Treatment Outcome, Infectious Diseases, Vietnam, MESH: Risk-Taking, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, addiction, MESH: Viral Load, Viral load, Cohort study, Adult, Drug, medicine.medical_specialty, Asia, [SDV.IMM] Life Sciences [q-bio]/Immunology, Anti-HIV Agents, media_common.quotation_subject, HIV prevention, Immunology, amphetamines, Medication Adherence, MESH: Methamphetamine, 03 medical and health sciences, Risk-Taking, MESH: Drug Users, Internal medicine, Humans, MSM, Editorial Comments, MESH: Humans, business.industry, HIV, MESH: Adult, Odds ratio, MESH: Medication Adherence, Confidence interval, MESH: Male, Treatment Adherence and Compliance, 030104 developmental biology, MESH: Substance Abuse, Intravenous, MESH: Vietnam, business, MESH: Female
Abstract: International audience; Objective: We assessed the association between methamphetamine use and lack of viral suppression among a cohort of HIV-seropositive persons who inject drugs (PWID) in Hai Phong, Vietnam.Design: Cohort study with random effects logit modeling and mediation analysis for antiretroviral therapy (ART) adherence.Methods: PWID were recruited from October 2016 to October 2017; HIV-seropositive PWID were enrolled in a cohort to assess HIV viral loads, changes in drug use, risk behaviors, and ART adherence during 24-month follow-up. Methamphetamine use in last 30 days was divided into three categories: 0 days (no use), 1-19 days (intermediate), and 20 or more days (heavy). Bivariate and a multivariable random effects logit models were used to assess the relationship between methamphetamine use and not being virally suppressed. We also assessed self-reported ART adherence as a mediating factor.Results: A total of 645 HIV-seropositive PWID were included at baseline; 95% male, average age 40 (SD = 6.4). At baseline, methamphetamine use in last 30 days was 64% no use, 32% intermediate use, 4% heavy use. Approximately 74% of PWID reported high/complete adherence; 76% were at viral suppression. In random effects analysis, recent methamphetamine use was associated with not being virally suppressed during follow-up (adjusted odds ratio: 1.84, 95% confidence interval: 1.06, 3.17); the effect was not explained by a mediating effect of self-reported adherence to ART.Conclusion: Recent methamphetamine use is associated with not being virally suppressed among PWID. The results of this study indicate the need for targeted interventions for methamphetamine use with special focus on those with HIV infection.
Published: 2020

13. How PrEP users constitute a community in the MSM population through their specific experience and management of stigmatization. The example of the French ANRS-PREVENIR study

Author: J. Ghosn, Stéphane Morel, Dominique Costagliola, Xavier Mabire, Costanza Puppo, Marie Préau, Bruno Spire, M. Genin, D Rojas Castro, Lydie Beniguel, Jean-Michel Molina, Dupuis, Christine, Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), 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], Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de maladies infectieuses et tropicales [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)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, Safe Sex, MESH: Sexual Behavior, Health (social science), [SDV]Life Sciences [q-bio], Social Stigma, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, 0302 clinical medicine, Social Norms, MESH: Sexual Partners, 030212 general & internal medicine, Prospective Studies, MESH: Anti-HIV Agents, Prospective cohort study, MESH: Qualitative Research, Qualitative Research, education.field_of_study, virus diseases, MESH: HIV Infections, Group dynamic, Focus Groups, MESH: Social Norms, PrEP, [SDV] Life Sciences [q-bio], Sexual Partners, MESH: Risk-Taking, community, France, 0305 other medical science, MESH: Social Stigma, Adult, medicine.medical_specialty, Social Psychology, Anti-HIV Agents, Sexual Behavior, Population, MESH: Stereotyping, Stigma (botany), MESH: Safe Sex, MESH: Homosexuality, Male, 03 medical and health sciences, Risk-Taking, medicine, Humans, Homosexuality, Male, education, Stereotyping, 030505 public health, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, HIV, MESH: Adult, MESH: Male, MESH: Prospective Studies, MESH: France, stigma, Family medicine, group dynamics, Pre-Exposure Prophylaxis, MESH: Focus Groups, business, Qualitative research, qualitative methods, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; The ANRS-PREVENIR (2017-2020) prospective cohort study aims to reduce the number of new HIV infections in the "Ile-de-France" region in France, by enrolling individuals at high risk of HIV infection and proposing daily and on-demand pre-exposure prophylaxis (PrEP). The qualitative component of the ANRS-PREVENIR study aimed to investigate social and relational evolutions associated with PrEP use in men who have sex with men (MSM). In 2018, 12 focus groups with MSM (n = 68) were conducted by a social sciences researcher in Paris. A thematic analysis was performed. Results showed that stigma concerning PrEP use is a complex issue, with various kinds of stigmatization being practiced, sometimes even by the wider MSM population and PrEP users themselves. All types of stigma identified were expressed in forms of verbal abuse which made PrEP use taboo. Inside the wider MSM population a PrEP-user "community" was identified which shared a certain complicity in terms of values and a positive attitude towards PrEP. The emergence of new intragroup and intergroup social norms should be taken into account by policy makers to promote a more positive image of PrEP users.
Published: 2020

14. What are the situational and behavioral factors associated with condomless anal sex without pre-exposure prophylaxis in MSM?

Author: Christian Chidiac, Mohamed Mimi, Marie Préau, Christel Protière, Catherine Capitant, Luis Sagaon-Teyssier, Jean-Michel Molina, Daniela Rojas Castro, Laurence Meyer, Cécile Tremblay, Marion Di Ciaccio, Bruno Spire, Marie Suzan-Monti, Dupuis, Christine, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Pantin, France] (Mission Innovation Recherche Expérimentation), Coalition Internationale Sida [Pantin, France] (Programme Recherche Communautaire), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), 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 de maladies infectieuses et tropicales [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)-Université Paris Cité (UPCité), Department of Infectious Diseases [Paris], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hopital Saint-Louis [AP-HP] (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)-Université Paris-Sud - Paris 11 (UP11), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, Safe Sex, 0301 basic medicine, Sexual partner, MESH: Sexual Behavior, [SDV]Life Sciences [q-bio], HIV Infections, Gee, law.invention, Condoms, Pre-exposure prophylaxis, 0302 clinical medicine, law, Immunology and Allergy, Medicine, MESH: Sexual Partners, 030212 general & internal medicine, MESH: Anti-HIV Agents, Generalized estimating equation, MESH: Middle Aged, MESH: HIV Infections, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Sexual Partners, Infectious Diseases, MESH: Risk-Taking, MESH: Young Adult, Viral load, Adult, Anti-HIV Agents, MESH: Unsafe Sex, Sexual Behavior, Immunology, MESH: Safe Sex, MESH: Homosexuality, Male, Young Adult, 03 medical and health sciences, MESH: Condoms, Risk-Taking, Condom, Humans, Homosexuality, Male, MESH: Humans, Unsafe Sex, business.industry, MESH: Adult, MESH: Male, Sexual intercourse, 030104 developmental biology, Attributable risk, Pre-Exposure Prophylaxis, business, Demography, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; Objective: This study aimed to identify situational and behavioral factors associated with condomless anal sex without on-demand PrEP in the open-label extension (OLE) study of the ANRS-IPERGAY trial.Methods: Univariable and multivariable modified Poisson regressions with a generalized estimating equation (GEE) were used. The attributable risk percentage for each explanatory variable and for condomless anal sex without PrEP was calculated.Results: In the OLE, 19% of anal intercourses were unprotected (i.e. no PrEP or condom). Of these, 85% were attributable to sexual intercourse with main partners and 47% with HIV-negative partners. The following factors were positively associated with condomless anal sex without PrEP: a depressive episode in the previous 12 months [aR (95% CI), P-value: 1.49 (1.02--2.17), 0.039], a higher number of sexual intercourses during the previous 4 weeks [1.01 [1.002--1.02], 0.014], and sexual intercourses under the influence of alcohol [1.45 (1.10--1.92), 0.008]. By contrast, condomless anal sex without PrEP was less frequent during sexual intercourses with known casual, unknown casual and multiple partners [0.20 (0.14--0.30)
Published: 2020

15. [HIV and cancer: Update 2020]

Author: Jean-Philippe Spano, Baptiste Abbar, Caroline Solas, Marianne Veyri, Isabelle Poizot-Martin, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), and Dupuis, Christine
Subjects: 0301 basic medicine, Cancer Research, Interactions médicamenteuses, Epidemiology, MESH: Drug Interactions, [SDV]Life Sciences [q-bio], Inhibiteurs des checkpoints immunitaires, Immune checkpoint inhibitor, MESH: Anus Neoplasms, 0302 clinical medicine, Medicine, MESH: Neoplasms, MESH: Anti-HIV Agents, Cancer, education.field_of_study, MESH: HIV Long-Term Survivors, Hematology, General Medicine, MESH: HIV Infections, 3. Good health, Épidémiologie, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, MESH: Immunotherapy, Adoptive, Screening, medicine.medical_specialty, Population, Context (language use), Drug interactions, 03 medical and health sciences, Radiology, Nuclear Medicine and imaging, Lung cancer, Intensive care medicine, education, Adverse effect, MESH: Humans, business.industry, Public health, HIV, VIH, medicine.disease, MESH: Lung Neoplasms, Clinical trial, MESH: France, 030104 developmental biology, Dépistage, Neoplasm, MESH: Antineoplastic Agents, business
Abstract: The HIV infection remains a serious public health concern in France and around the world. Cancers are frequent among people living with HIV (PLWH) and have become the leading cause of mortality among this population in France. Certain non-AIDS-defining cancers are much more common among PLWH, such as anal carcinoma, Hodgkin lymphoma, hepatocellular carcinoma and lung cancer. The incidence of cancer among PLWH depending on various factors, virological control under combined antiretrovial therapies (cART), exposure prevention to oncogenic virus and toxics are of utmost importance, such as the implementation of specific screening programmes. Drug interactions between cART and oncologic treatments can lead to serious adverse effects or to a reduction in the therapeutic effects, therefore they require a close monitoring. The PLWH have been excluded from the oncologic clinical trials assessing the efficacy and toxicity profile of the immune checkpoints inhibitors (ICPi) because of an increased theoretical risk of inducing adverse events and a feared lack of efficacy in the immunocompromised population. However, the mostly retrospective clinical data reporting the use of ICPi among PLWH are somewhat reassuring with a safety and efficacy profile similar to what observed in HIV-negative patients. Regarding the "shock and kill" anti-HIV effects of ICPi, the preliminary clinical data available are still modest and relatively disappointing despite encouraging results obtained in vitro. HIV-associated cancers represent a particular care challenge due to the multiple comorbidities in the population and the high risk of drug interactions, thus the CANCERVIH national network is of particular interest within this context., L'infection par le VIH reste un problème majeur de santé publique en France et dans le monde. La survenue de cancer est fréquente chez les personnes vivant avec le VIH (PVVIH) et représente la première cause de mortalité dans cette population en France. Certains cancers non classant SIDA sont beaucoup plus fréquents chez les PVVIH, comme le carcinome anal, la maladie de Hodgkin, le carcinome hépatocellulaire et le cancer bronchique. Le risque de cancer chez les PVVIH dépendant de nombreux facteurs, le contrôle virologique, la prévention de l'exposition aux virus oncogènes et aux toxiques sont très importants, tout comme la mise en place de programmes de dépistage spécifiques. Les interactions médicamenteuses entre antirétroviraux et traitements antinéoplasiques pouvant entraîner un sur risque de toxicité ou une perte d'efficacité sont particulièrement à surveiller chez les PVVIH. Du fait d'un risque théorique accru de toxicité et de manque d'efficacité, les PVVIH ont été exclues des grandes études sur les inhibiteurs des checkpoints immunitaires (ICPi). Cependant, les données majoritairement rétrospectives sur l'utilisation des ICPi chez les PVVIH sont rassurantes avec un profil de toxicité et d'efficacité antitumorale similaire à celui observé en population générale. Quant à l'effet des ICPi dans une stratégie du « shock and kill » anti-VIH les tout premiers résultats disponibles dans la littérature semblent décevants malgré des résultats obtenus in vitro très encourageants. La complexité de prise en charge oncologique de cette population aux nombreux comorbidités nécessite une collaboration pluridisciplinaire étroite, le réseau national CANCERVIH prend tout son sens dans ce contexte.
Published: 2020

16. VIH et cancer : mise au point en 2020

Author: Abbar, Baptiste, Veyri, Marianne, Solas, Caroline, Poizot-Martin, Isabelle, Spano, Jean-Philippe, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité des Virus Emergents (UVE), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), 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'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], and Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )
Subjects: Lung Neoplasms, Interactions médicamenteuses, Epidemiology, Anti-HIV Agents, MESH: Drug Interactions, [SDV]Life Sciences [q-bio], Inhibiteurs des checkpoints immunitaires, Antineoplastic Agents, HIV Infections, Immune checkpoint inhibitor, Immunotherapy, Adoptive, MESH: Anus Neoplasms, HIV Long-Term Survivors, Neoplasms, Humans, MESH: Neoplasms, Drug Interactions, MESH: Anti-HIV Agents, Cancer, MESH: HIV Long-Term Survivors, MESH: Humans, HIV, VIH, MESH: HIV Infections, Anus Neoplasms, MESH: Lung Neoplasms, Épidémiologie, MESH: France, Dépistage, MESH: Immunotherapy, Adoptive, Screening, Neoplasm, MESH: Antineoplastic Agents, France
Abstract: International audience; The HIV infection remains a serious public health concern in France and around the world. Cancers are frequent among people living with HIV (PLWH) and have become the leading cause of mortality among this population in France. Certain non-AIDS-defining cancers are much more common among PLWH, such as anal carcinoma, Hodgkin lymphoma, hepatocellular carcinoma and lung cancer. The incidence of cancer among PLWH depending on various factors, virological control under combined antiretrovial therapies (cART), exposure prevention to oncogenic virus and toxics are of utmost importance, such as the implementation of specific screening programmes. Drug interactions between cART and oncologic treatments can lead to serious adverse effects or to a reduction in the therapeutic effects, therefore they require a close monitoring. The PLWH have been excluded from the oncologic clinical trials assessing the efficacy and toxicity profile of the immune checkpoints inhibitors (ICPi) because of an increased theoretical risk of inducing adverse events and a feared lack of efficacy in the immunocompromised population. However, the mostly retrospective clinical data reporting the use of ICPi among PLWH are somewhat reassuring with a safety and efficacy profile similar to what observed in HIV-negative patients. Regarding the "shock and kill" anti-HIV effects of ICPi, the preliminary clinical data available are still modest and relatively disappointing despite encouraging results obtained in vitro. HIV-associated cancers represent a particular care challenge due to the multiple comorbidities in the population and the high risk of drug interactions, thus the CANCERVIH national network is of particular interest within this context.; L'infection par le VIH reste un problème majeur de santé publique en France et dans le monde. La survenue de cancer est fréquente chez les personnes vivant avec le VIH (PVVIH) et représente la première cause de mortalité dans cette population en France. Certains cancers non classant SIDA sont beaucoup plus fréquents chez les PVVIH, comme le carcinome anal, la maladie de Hodgkin, le carcinome hépatocellulaire et le cancer bronchique. Le risque de cancer chez les PVVIH dépendant de nombreux facteurs, le contrôle virologique, la prévention de l'exposition aux virus oncogènes et aux toxiques sont très importants, tout comme la mise en place de programmes de dépistage spécifiques. Les interactions médicamenteuses entre antirétroviraux et traitements antinéoplasiques pouvant entraîner un sur risque de toxicité ou une perte d'efficacité sont particulièrement à surveiller chez les PVVIH. Du fait d'un risque théorique accru de toxicité et de manque d'efficacité, les PVVIH ont été exclues des grandes études sur les inhibiteurs des checkpoints immunitaires (ICPi). Cependant, les données majoritairement rétrospectives sur l'utilisation des ICPi chez les PVVIH sont rassurantes avec un profil de toxicité et d'efficacité antitumorale similaire à celui observé en population générale. Quant à l'effet des ICPi dans une stratégie du « shock and kill » anti-VIH les tout premiers résultats disponibles dans la littérature semblent décevants malgré des résultats obtenus in vitro très encourageants. La complexité de prise en charge oncologique de cette population aux nombreux comorbidités nécessite une collaboration pluridisciplinaire étroite, le réseau national CANCERVIH prend tout son sens dans ce contexte.
Published: 2019

17. Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor

Author: Jens Bohne, Daniel Todt, Steppich K, Sergej Franz, Angelina Malassa, Thomas Zillinger, Eike Steinmann, Xu S, Nicoletta Casartelli, Passos, Christine Goffinet, Winfried Barchet, Wachs As, Oliver Schwartz, Schilling H, Kathrin Sutter, Ulf Dittmer, Centre for Experimental and Clinical Infection Research [Hanover] (TWINCORE), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Institute of Clinical Chemistry and Clinical Pharmacology [Bonn, Allemagne], University of Bonn, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Ruhr University Bochum (RUB), University of Duisburg-Essen, German Centre for Infection Research (DZIF), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Vânia Passos and Sergej Franz are supported by the Infection Biology International Ph.D. Program of the Hannover Biomedical Research School. Vânia Passos is supported by the GABBA Ph.D. Program and the Fundação para a Ciência e Tecnologia (FCT). Thomas Zillinger and Winfried Barchet acknowledge Bonfor and DZIF funding and German Research Foundation (Deutsche Forschungsgemeinschaft [DFG]) grants EXC1023: ImmunoSensation and CRCs 670 and 704. This work is supported by DFG funding to Christine Goffinet (Collaborative Research Centre SFB900, Microbial Persistence and its Control, project C8 and Priority Program 1923, Innate Sensing and Restriction of Retroviruses, GO2153/4 grant) and funding from the HZI and the Berlin Institute of Health (BIH) to Christine Goffinet., Universidade do Porto = University of Porto, Universität Bonn = University of Bonn, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], and TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
Subjects: MESH: Gene Editing, MESH: CRISPR-Cas Systems, T-Lymphocytes, Mutant, Medizin, HIV Infections, Endogeny, Jurkat cells, Epitope, MESH: HIV-1, MESH: Genotype, Gene Knockout Techniques, SERINC5, MESH: nef Gene Products, Human Immunodeficiency Virus, MESH: Anti-HIV Agents, Internalization, media_common, MESH: Gene Knockout Techniques, Gene Editing, 0303 health sciences, human immunodeficiency virus, 030302 biochemistry & molecular biology, virus diseases, MESH: HIV Infections, MESH: Gene Expression Regulation, Virus-Cell Interactions, 3. Good health, Cell biology, interferons, MESH: HEK293 Cells, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Virion, MESH: Membrane Proteins, MESH: Interferon-alpha, Genotype, Anti-HIV Agents, media_common.quotation_subject, Immunology, Alpha interferon, Heterologous, Biology, Microbiology, Cell Line, 03 medical and health sciences, Virology, Nitriles, Humans, nef Gene Products, Human Immunodeficiency Virus, antiviral factor, CRISPR/Cas9, 030304 developmental biology, Nef, MESH: Humans, Cell Membrane, MESH: Host-Pathogen Interactions, Virion, Interferon-alpha, Membrane Proteins, Subcellular localization, MESH: Cell Line, HEK293 Cells, Pyrimidines, MESH: T-Lymphocytes, Gene Expression Regulation, Insect Science, HIV-1, Pyrazoles, CRISPR-Cas Systems, MESH: Pyrazoles, MESH: Cell Membrane
Abstract: SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions., When expressed in virus-producing cells, the cellular multipass transmembrane protein SERINC5 reduces the infectivity of HIV-1 particles and is counteracted by HIV-1 Nef. Due to the unavailability of an antibody of sufficient specificity and sensitivity, investigation of SERINC5 protein expression and subcellular localization has been limited to heterologously expressed SERINC5. We generated, via CRISPR/Cas9-assisted gene editing, Jurkat T-cell clones expressing endogenous SERINC5 bearing an extracellularly exposed hemagglutinin (HA) epitope [Jurkat SERINC5(iHA knock-in) T cells]. This modification enabled quantification of endogenous SERINC5 protein levels and demonstrated a predominant localization in lipid rafts. Interferon alpha (IFN-α) treatment enhanced cell surface levels of SERINC5 in a ruxolitinib-sensitive manner in the absence of modulation of mRNA and protein quantities. Parental and SERINC5(iHA knock-in) T cells shared the ability to produce infectious wild-type HIV-1 but not an HIV-1 Δnef mutant. SERINC5-imposed reduction of infectivity involved a modest reduction of virus fusogenicity. An association of endogenous SERINC5 protein with HIV-1 Δnef virions was consistently detectable as a 35-kDa species, as opposed to heterologous SERINC5, which presented as a 51-kDa species. Nef-mediated functional counteraction did not correlate with virion exclusion of SERINC5, arguing for the existence of additional counteractive mechanisms of Nef that act on virus-associated SERINC5. In HIV-1-infected cells, Nef triggered the internalization of SERINC5 in the absence of detectable changes of steady-state protein levels. These findings establish new properties of endogenous SERINC5 expression and subcellular localization, challenge existing concepts of HIV-1 Nef-mediated antagonism of SERINC5, and uncover an unprecedented role of IFN-α in modulating SERINC5 through accumulation at the cell surface. IMPORTANCE SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions.
Published: 2019

18. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial

Author: Laurence Meyer, Julie Chas, Jean-Guy Baril, Véronique Doré, Michel Morin, Jean-Pierre Aboulker, Marine Saouzanet, Isabelle Durant-Zaleski, Marie Suzan-Monti, Emmanuelle Netzer, Françoise Euphrasie, Nathalie Bajos, Séverine Gibowski, Soizic Le Mestre, Gilles Peytavin, Jean-François Delfraissy, Constance Delaugerre, David Thompson, Brigitte Guillon, Gilles Pialoux, Alpha Diallo, Nicolas Etien, Christian Chidiac, Michel Besnier, Isabelle Charreau, Benoit Trottier, Baptiste Demoulin, Julie Timsit, Bruno Spire, Joanne Otis, Laurent Cotte, Julien Fonsart, W. Rozenbaum, Mark A. Wainberg, Gabriel Girard, Eric Cua, Guillemette Antoni, Daniela Rojas Castro, Catherine Capitant, Luis Sagaon-Teyssier, Antoine Cheret, Marie-Christine Simon, Cécile Tremblay, Nicolas Leturque, Johan Binesse, Diane Carette, Valérie Foubert, Anaïs Mennecier, Grégoire Cattin, Jean-Michel Molina, Yacine Saïdi, Nicolas Lorente, Elias Choucair, François Raffi, Cecile Rabian, Armelle Pasquet, Marie Préau, Thomas Huleux, 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, Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Archet 2 [Nice] (CHU), Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), 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 d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Gustave Dron [Tourcoing], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé (Sidaction), Gilead Sciences, and the Bill & Melinda Gates Foundation., ANRS IPERGAY study group: Jean-Pierre Aboulker, Nathalie Bajos, Jean-Guy Baril, Michel Besnier, Johan Binesse, Diane Carette, Grégoire Cattin, Antoine Chéret, Christian Chidiac, Elias Choucair, Jean-François Delfraissy, Baptiste Demoulin, Alpha Diallo, Isabelle Durant-Zaleski, Véronique Doré, Nicolas Etien, Françoise Euphrasie, Julien Fonsart, Valérie Foubert, Séverine Gibowski, Gabriel Girard, Brigitte Guillon, Soizic Le Mestre, France Lert, Nicolas Leturque, Nicolas Lorente, Anaïs Mennecier, Michel Morin, Emmanuelle Netzer, Joanne Otis, Armelle Pasquet, Gilles Peytavin, Gilles Pialoux, Marie Préau, Cécile Rabian, Willy Rozenbaum, Luis Sagaon-Teyssier, Yacine Saïdi, Marine Saouzanet, Marie-Christine Simon, Marie Suzan-Monti, David Thompson, Julie Timsit, Benoît Trottier, Mark Wainberg, Dupuis, Christine, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, MESH: Sexual Behavior, Epidemiology, [SDV]Life Sciences [q-bio], HIV Infections, Men who have sex with men, MESH: HIV-1, Pre-exposure prophylaxis, Sexual and Gender Minorities, 0302 clinical medicine, MESH: Tenofovir, Medicine, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Incidence, MESH: Anti-HIV Agents, education.field_of_study, Incidence (epidemiology), Incidence, MESH: HIV Infections, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Sexual and Gender Minorities, Infectious Diseases, Pill, France, medicine.drug, Adult, medicine.medical_specialty, Canada, Anti-HIV Agents, Sexual Behavior, Immunology, Population, Placebo, Emtricitabine, Medication Adherence, MESH: Homosexuality, Male, 03 medical and health sciences, Double-Blind Method, MESH: Canada, Virology, Internal medicine, Humans, Homosexuality, Male, education, Tenofovir, MESH: Humans, business.industry, MESH: Adult, MESH: Medication Adherence, 030112 virology, MESH: Male, MESH: France, Sexual intercourse, HIV-1, Pre-Exposure Prophylaxis, business, MESH: Pre-Exposure Prophylaxis
Abstract: Summary Background ANRS IPERGAY found that on-demand pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine was associated with an 86% relative reduction of HIV-1 incidence compared with placebo among men who have sex with men at high risk of HIV. We aimed to investigate whether on-demand PrEP was similarly effective among individuals with lower exposure to HIV risk. Methods Participants in the ANRS IPERGAY trial were randomly assigned to receive PrEP (fixed-dose combination of 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine per pill) or placebo. The primary endpoint was the diagnosis of HIV-1 infection. Pill uptake was assessed by counting returned pills at each follow-up and by estimating tenofovir concentration from frozen plasma samples. Participants were interviewed at each visit to assess the pattern of PrEP use. All participants enrolled in the modified intention-to-treat population of the double-blind phase of the ANRS IPERGAY trial were eligible for this post-hoc analysis. We calculated the total follow-up time for periods of less frequent sexual intercourse with high PrEP adherence (15 pills or fewer per month taken systematically or often during sexual intercourse). To estimate the time of HIV acquisition, fourth-generation HIV-1/2 ELISA assays, plasma HIV-1 RNA assays, and western blot analyses were done with use of frozen samples, and the stage of HIV infection was defined according to Fiebig staging. HIV incidence was compared between the two treatment groups among individuals who had less frequent sexual intercourse with high PrEP adherence. The ANRS IPERGAY trial is registered with ClinicalTrials.gov , NCT01473472 . Findings 400 participants who were randomly assigned to receive PrEP (n=199) or placebo (n=201) between Feb 22, 2012, and Oct 17, 2014, were included in this analysis. 270 participants had at least one period of less frequent sexual intercourse with high PrEP adherence during the study, representing 134 person-years of follow-up and 31% of the total study follow-up. During these periods, participants in both groups reported a median of 5·0 (IQR 2·0–10·0) episodes of sexual intercourse per month and used a median of 9·5 (6·0–13·0) pills per month. Six HIV-1 infections were diagnosed in the placebo group (HIV incidence of 9·2 per 100 person-years; 95% CI 3·4–20·1) and none were diagnosed in the tenofovir disoproxil fumarate plus emtricitabine arm (HIV incidence of 0 per 100 person-years; 0–5·4; p=0·013), with a relative reduction of HIV incidence of 100% (95% CI 39–100). Interpretation A choice between daily or on-demand PrEP regimens could be offered to men who have sex with men who have less frequent sexual intercourse. Funding ANRS (France Recherche Nord and Sud Sida-HIV Hepatites), the Canadian HIV Trials Network, Fonds Pierre Berge (Sidaction), Gilead Sciences, and the Bill & Melinda Gates Foundation.
Published: 2019

19. The 3-O-(3',3'-dimethylsuccinyl) derivative of betulinic acid (DSB) inhibits the assembly of virus-like particles in HIV-1 Gag precursor-expressing cells

Author: Sandrina Dafonseca, Armand Blommaert, Pascale CORIC, Saw See Hong, Serge Bouaziz, Pierre Boulanger, Centre de recherche, CHU Montréal, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rétrovirus et Pathologie Comparée (RPC), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Bouaziz, Serge, Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)
Subjects: Models, Molecular, MESH: Protein Precursors, MESH: Virus Assembly, Anti-HIV Agents, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Succinates, Spodoptera, Cell Line, MESH: Dose-Response Relationship, Drug, MESH: HIV-1, Structure-Activity Relationship, MESH: Protein Structure, Tertiary, MESH: Structure-Activity Relationship, Animals, MESH: Animals, Protein Precursors, MESH: Anti-HIV Agents, MESH: Spodoptera, Dose-Response Relationship, Drug, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Virus Assembly, MESH: Triterpenes, Succinates, Triterpenes, Protein Structure, Tertiary, MESH: Cell Line, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Baculoviridae, HIV-1, Baculoviridae, MESH: Models, Molecular
Abstract: The 3-O-(3',3'-dimethylsuccinyl) derivative of betulinic acid (DSB) blocks HIV-1 maturation by interfering with viral protease (PR) at the capsid (CA)-SP1 cleavage site, a crucial region in HIV-1 morphogenesis.We analysed the effect of DSB on the assembly of HIV-1 Gag precursor (Pr55Gag(HIV)) into membrane-enveloped virus-like particles (VLP) in baculovirus-infected cells expressing Pr55Gag(HIV), in a cellular context devoid of viral PR.DSB showed a dose-dependent negative effect on VLP assembly, with an IC50 approximately 10 microM. The DSB inhibitory effect was p6-independent and was also observed for intracellular assembly of non-N-myristoylated Gag core-like particles. HIV-1 VLP assembled in the presence of DSB exhibited a lower stability of their inner cores upon membrane delipidation compared with control VLP, suggesting weaker Gag-Gag interactions. DSB also inhibited the assembly of simian immunodeficiency virus SLVmac251 VLP, although with a twofold lower efficacy (IC50 approximately 20 microM). No detectable inhibitory activity was observed for murine leukaemia virus (MLV) VLP; however, fusion of the SP1-NC-p6 domains from HIV-1 to the matrix (MA)-CA domains from MLV conferred DSB sensitivity to the chimaeric Gag precursor Pr72Gag(MLV-HIV) (IC50 = 30 microM). This observation suggested that the main DSB target on Pr55Gag was the SP1 domain, but the higher degree of DSB resistance for Pr72Gag(MLV-HIV) compared with Pr55Gag(HIV) implied that other upstream Gag region(s) might contribute to DSB reactivity.Sequence alignment and three-dimensional modelling by homology of the CA-SP1-NC junction in HIV-1, SLVmac251 and Pr72Gag(MLV-HIV) suggested that a higher hydrophilic character of the CA region immediately upstream to the HIV-1 CA-SP1 junction, as occurred in Pr72Gag(MLV-HIV), correlated with a lower DSB sensitivity.
Published: 2019

20. Detection of pretreatment minority HIV-1 reverse transcriptase inhibitor-resistant variants by ultra-deep sequencing has a limited impact on virological outcomes

Author: Xin Zheng, Lishi Bai, Hongyan Lu, Yan Liu, Hao Wu, Chun Huang, Ruolei Xin, Tong Zhang, Lili Dai, Lijun Sun, Lifeng Liu, Fabrizio Mammano, Bin Su, Capital University of Medical Sciences [Beijing] (CUMS), EZKIT L.L.C. [Honolulu, HI, USA], Beijing Center for Disease Control and Prevention (Beijing CDC), Beijing Center for Disease Control and Prevention, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Mammano, Fabrizio
Subjects: 0301 basic medicine, Male, MESH: Treatment Failure, [SDV]Life Sciences [q-bio], HIV Infections, Drug resistance, Cohort Studies, MESH: HIV-1, chemistry.chemical_compound, Sexual and Gender Minorities, MESH: Single Molecule Imaging, 0302 clinical medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, MESH: Genetic Variation, MESH: Anti-HIV Agents, MESH: Cohort Studies, MESH: High-Throughput Nucleotide Sequencing, education.field_of_study, MESH: Drug Resistance, Viral, Reverse-transcriptase inhibitor, Lamivudine, High-Throughput Nucleotide Sequencing, MESH: HIV Infections, Viral Load, Single Molecule Imaging, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Sexual and Gender Minorities, MESH: Leukocytes, Mononuclear, Infectious Diseases, MESH: Young Adult, MESH: RNA, Viral, RNA, Viral, Reverse Transcriptase Inhibitors, MESH: Viral Load, medicine.drug, Microbiology (medical), Adult, MESH: Mutation, Anti-HIV Agents, 030106 microbiology, Population, DNA sequencing, Virus, 03 medical and health sciences, Young Adult, Drug Resistance, Viral, Humans, education, Pharmacology, MESH: Humans, business.industry, RNA, Genetic Variation, MESH: Adult, Virology, MESH: Male, chemistry, Mutation, HIV-1, Leukocytes, Mononuclear, MESH: Reverse Transcriptase Inhibitors, business, DNA
Abstract: International audience; Ultra-deep sequencing (UDS) is a powerful tool for exploring the impact on virological outcome of minority variants with low frequencies, some even ,1% of the virus population. Here, we compared HIV-1 minority variants at baseline, through plasma RNA and PBMC DNA analyses, and the dominant variants at the virological failure (VF) point, to evaluate the impact of minority drug-resistant variants (MDRVs) on virological outcomes. Methods: Single-molecule real-time sequencing (SMRTS) was performed on baseline RNA and DNA. The Stanford HIV-1 drug resistance database was used for the identification and evaluation of drug resistanceassociated mutations (DRAMs). Results: We classified 50 patients into virological success (VS) and VF groups. We found that the rates of reverse transcriptase inhibitor (RTI) DRAMs determined by SMRTS did not differ significantly within or between groups, whether based on RNA or DNA analyses. There was no significant difference in the level of resistance to specific drugs between groups, in either DNA or RNA analyses, except for the DNA-based analysis of lamivudine, for which there was a trend towards a higher prevalence of intermediate/high-level resistance in the VF group. The RNA MDRVs corresponded to DNA MDRVs, except for M100I and Y188H. Sequencing from DNA appeared to be more sensitive than from RNA to detect MDRVs. Conclusions: Detection of pretreatment minority HIV-1 RTI-resistant variants by UDS showed that MDRVs at baseline were not significantly associated with virological outcome. However, HIV-1 DNA sequencing by UDS was useful for detecting pretreatment drug resistance mutations in patients, potentially affecting virological responses, suggesting a potential clinical relevance for ultra-deep DNA sequencing.
Published: 2019

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

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

22. Cellular Determinants of HIV Persistence on Antiretroviral Therapy

Author: Jose Carlos Valle-Casuso, Anastassia Mikhailova, Asier Sáez-Cirión, HIV, Inflammation et persistance, Institut Pasteur [Paris], HIV, Inflammation et persistance - HIV, Inflammation and Persistence, and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Programmed cell death, Myeloid, [SDV]Life Sciences [q-bio], Cell, HIV reservoirs, Human immunodeficiency virus (HIV), MESH: T-Lymphocyte Subsets, Biology, medicine.disease_cause, Dendritic cells, Cell survival, Virus, Persistence (computer science), MESH: HIV-1, 03 medical and health sciences, 0302 clinical medicine, HIV susceptibility, MESH: Receptors, HIV, medicine, MESH: Immune Evasion, CD4+ T-cell subsets, MESH: Anti-HIV Agents, MESH: Viremia, Turnover potential, MESH: Drug Resistance, Viral, MESH: Humans, Macrophages, MESH: Apoptosis, MESH: Virus Replication, MESH: Virus Latency, MESH: HIV Infections, MESH: Myeloid Cells, Antiretroviral therapy, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, T cell subset, MESH: Viral Load, 030217 neurology & neurosurgery
Abstract: International audience; The era of antiretroviral therapy has made HIV-1 infection a manageable chronic disease for those with access to treatment. Despite treatment, virus persists in tissue reservoirs seeded with long-lived infected cells that are resistant to cell death and immune recognition. Which cells contribute to this reservoir and which factors determine their persistence are central questions that need to be answered to achieve viral eradication. In this chapter, we describe how cell susceptibility to infection, resistance to cell death, and immune-mediated killing as well as natural cell life span and turnover potential are central components that allow persistence of different lymphoid and myeloid cell subsets that were recently identified as key players in harboring latent and actively replicating virus. The relative contribution of these subsets to persistence of viral reservoir is described, and the open questions are highlighted.
Published: 2018

23. Impact of age-related comorbidities on five-year overall mortality among elderly HIV-infected patients in the late HAART era — Role of chronic renal disease

Author: Maxime HENTZIEN, Dramé, M., Allavena, C., Jacomet, C., Valantin, A., André Cabié, Cuzin, L., Rey, D., Pugliese, P., Bani-Sadr, F., Hentzien, F., Dramé, D., Allavena, A., Centre Hospitalier Universitaire de Reims (CHU Reims), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service des Maladies Infectieuses et Tropicales [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France]-Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Nouvel Hôpital Civil de Strasbourg, Service d'infectiologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), IER - Institut d'Economie Rurale (IER), IER, Department of Genetics, Biology and Biochemistry, University of Turin, Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), Service des maladies infectieuses [Clermont-Ferrand], CHU Clermont-Ferrand, 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), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), 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), and CHU Strasbourg
Subjects: Male, Aging, Medicine (miscellaneous), HIV Infections, MESH: Comorbidity, Comorbidity, MESH: Antiretroviral Therapy, Highly Active, Cohort Studies, surgery, MESH: Proportional Hazards Models, MESH: Cause of Death, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Cause of Death, Neoplasms, Prevalence, MESH: Aging, MESH: Neoplasms, Prospective Studies, 030212 general & internal medicine, MESH: Anti-HIV Agents, Prospective cohort study, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, MESH: Aged, 2. Zero hunger, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, Nutrition and Dietetics, Mortality rate, Hazard ratio, MESH: HIV Infections, Hepatitis C, Middle Aged, Hepatitis B, 3. Good health, Cardiovascular Diseases, MESH: Fibrosis, Cohort, Female, 030211 gastroenterology & hepatology, France, Cohort study, medicine.medical_specialty, MESH: Diabetes Mellitus, Anti-HIV Agents, MESH: Renal Insufficiency, Chronic, valves, 03 medical and health sciences, Internal medicine, Diabetes Mellitus, medicine, Humans, Renal Insufficiency, Chronic, Intensive care medicine, MESH: Prevalence, Aged, Proportional Hazards Models, MESH: Hepatitis C, MESH: Humans, business.industry, MESH: Cardiovascular Diseases, medicine.disease, Fibrosis, mortality, infection, MESH: Male, MESH: Prospective Studies, MESH: France, prognosis, Geriatrics and Gerontology, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; To identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV).; A prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012).; The Dat'AIDS cohort involving 12 French hospitals.; All actively followed HIV-1 infected patients aged 60 or older.; The study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox's Proportional Hazards model was used for multivariate analysis.; Among 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patient-years). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p
Published: 2015

24. Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial

Author: Michal Odermarsky, Andrea Antinori, Nina Friis-Moller, Jean-michel Molina, Manuel Marquez, Magnus Gisslen, Mili Estee Torok, Clifford Leen, CARLO FEDERICO PERNO, Vicente Soriano, Mark Boyd, Pythia Nieuwkerk, Linos Vandekerckhove, Anne-Laure Knellwolf, Juan González-García, MAURIZIO MASSELLA, Elizabeth C George, STEFANO VELLA, André Cabié, Laura Richert, Juan Berenguer, Hernando Knobel, Jose Arribas, Julie Fox, Joaquín Portilla, Maladies infectieuses et tropicales, Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Inserm, 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), Development and Differentiation, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Stockholm University Library (SUB), Stockholm University, Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Aménagement, Développement, Environnement, Santé et Sociétés (ADES), Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne, 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), DARMIGNY, Sandrine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), Raffi, Franã§oi, Babiker, Abdel G., Richert, Laura, Molina, Jean michel, George, Elizabeth C., Antinori, Andrea, Arribas, Jose R., Grarup, Jesper, Hudson, Fleur, Schwimmer, Christine, Saillard, Juliette, Wallet, Cã©drick, Jansson, Per O., Allavena, Clotilde, Van Leeuwen, Remko, Delfraissy, Jean franã§oi, Vella, Stefano, Chãªne, Geneviãve, Pozniak, Anton, Neat001/anrs143 Study, Group, Castagna, Antonella, Global Health, Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam Public Health, Medical Psychology, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], MESH: Sulfonamides, Lopinavir/ritonavir, HIV Infections, Kaplan-Meier Estimate, Pharmacology, Deoxycytidine, MESH: HIV-1, Emtricitabine, MESH: Anti-HIV Agents, MESH: Treatment Outcome, Darunavir, media_common, Sulfonamides, MESH: Middle Aged, MESH: Drug Resistance, Viral, Medicine (all), Standard treatment, MESH: HIV Infections, General Medicine, Middle Aged, Pyrrolidinones, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Drug Therapy, Combination, Female, MESH: Cholesterol, HDL, MESH: Organophosphonates, MESH: Cholesterol, LDL, medicine.drug, Adult, medicine.medical_specialty, MESH: Adenine, Anti-HIV Agents, Organophosphonates, MESH: Pyrrolidinones, Raltegravir Potassium, Internal medicine, Drug Resistance, Viral, medicine, Humans, media_common.cataloged_instance, European union, Tenofovir, MESH: Kaplan-Meier Estimate, MESH: Humans, Ritonavir, business.industry, Adenine, MESH: Deoxycytidine, Cholesterol, HDL, MESH: Adult, Cholesterol, LDL, Raltegravir, MESH: Male, CD4 Lymphocyte Count, MESH: Drug Therapy, Combination, Regimen, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, MESH: Ritonavir, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: Summary Background Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Methods Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir–emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962. Findings Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112–133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI −0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively). Interpretation Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. Funding European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.
Published: 2014

25. Capsid proteins of enveloped viruses as antiviral drug targets

Author: Klaus Klumpp, Thibaut Crépin, UR 0874 Unité de recherche sur l'Ecosystème Prairial, Institut National de la Recherche Agronomique (INRA)-Unité de recherche sur l'Ecosystème Prairial (UREP)-Ecologie des Forêts, Prairies et milieux Aquatiques (EFPA), Institut National de la Recherche Agronomique (INRA), Unit of Virus Host Cell Interactions (UVHCI), and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Viral capsid assembly, Anti-HIV Agents, medicine.drug_class, viruses, HIV Infections, Biology, Protein–protein interaction, MESH: HIV-1, Viral envelope, Viral entry, Virology, Viral structural protein, medicine, Animals, Humans, MESH: Animals, MESH: Anti-HIV Agents, MESH: Capsid Proteins, MESH: Humans, MESH: HIV Infections, Peplomer, Cell biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Capsid, HIV-1, Capsid Proteins, Antiviral drug
Abstract: International audience; Viral proteins have enabled the design of selective and efficacious treatments for viral diseases. While focus in this area has been on viral enzymes, it appears that multifunctional viral proteins may be even more susceptible to small molecule interference. As exemplified by HIV capsid, small molecule inhibitors can bind to multiple binding sites on the capsid protein and induce or prevent protein interactions and conformational changes. Resistance selection is complicated by the fact that the capsid proteins have to engage in different protein interactions at different times of the life cycle. Viral capsid assembly and disassembly have therefore emerged as highly sensitive processes that could deliver a new generation of antiviral agents across viral diseases.
Published: 2014

26. Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)

Author: Charlotte Charpentier, Véronique Joly, Carine Grondin, Sophie Tabuteau, Yazdan Yazdanpanah, François Raffi, André Cabié, Catherine Fagard, Patrick Yeni, Geneviève Chêne, Nathalie Colin de Verdiere, Diane Descamps, Service de maladies infectieuses et tropicales, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Laboratoire de Virologie, 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), Modélisation, Aide à la Décision, et Coût-Efficacité en Maladies Infectieuses (ATIP-Avenir Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Infectieuses et Tropicales, 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 Diderot - Paris 7 (UPD7), Maladies infectieuses et tropicales, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), 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), ANRS (French National Agency for Research on AIDS and Viral Hepatitis), ANRS 130 Apollo Trial Group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Le Corre, Morgane, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2
Subjects: CD4-Positive T-Lymphocytes, Cyclopropanes, Male, Enfuvirtide, MESH: CD4 Lymphocyte Count, MESH: HIV Envelope Protein gp41, HIV Infections, Deoxycytidine, MESH: Antiretroviral Therapy, Highly Active, Lopinavir, MESH: HIV-1, chemistry.chemical_compound, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Emtricitabine, Pharmacology (medical), 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Peptide Fragments, MESH: Treatment Outcome, 0303 health sciences, MESH: Lopinavir, MESH: CD4-Positive T-Lymphocytes, virus diseases, MESH: HIV Infections, Viral Load, HIV Envelope Protein gp41, 3. Good health, Drug Combinations, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Treatment Outcome, Infectious Diseases, MESH: RNA, Viral, MESH: Benzoxazines, Alkynes, RNA, Viral, Female, medicine.symptom, MESH: Viral Load, MESH: Organophosphonates, Viral load, medicine.drug, Adult, medicine.medical_specialty, MESH: Adenine, MESH: Immune Tolerance, Efavirenz, Anti-HIV Agents, Organophosphonates, Antiviral Agents, Asymptomatic, 03 medical and health sciences, Multicenter trial, Internal medicine, Immune Tolerance, medicine, Humans, Tenofovir, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Drug Combinations, Pharmacology, MESH: Humans, Ritonavir, 030306 microbiology, business.industry, Adenine, MESH: Deoxycytidine, MESH: Adult, MESH: Male, Peptide Fragments, Benzoxazines, CD4 Lymphocyte Count, Surgery, chemistry, HIV-1, MESH: Ritonavir, business, MESH: Female
Abstract: We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of 3 or stage B/C disease with CD4 counts of 3 . Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm 3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm 3 , and the median HIV-1 RNA load was 5.4 log 10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm 3 at week 24 were 34% and 38% in the ENF and control arms, respectively ( P = 0.53). The proportions of patients with HIV-1 RNA loads of P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up ( P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression.
Published: 2013

27. Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis

Author: Taieb, Fabien, Madec, Yoann, Cournil, Amandine, Delaporte, Eric, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), 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), No funding., We would to thank Ms Sandrine Royer-Devaux for her support in the article search and Ms Rebecca Grant and Ms Anna Louise Funk for their thorough proof reading and editing., Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Montpellier 1 (UM1)-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)
Subjects: RNA viruses, Epidemiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, HIV Infections, Pathology and Laboratory Medicine, Cohort Studies, Geographical Locations, Mathematical and Statistical Techniques, Immunodeficiency Viruses, Medicine and Health Sciences, Public and Occupational Health, MESH: Anti-HIV Agents, lcsh:Science, MESH: Cohort Studies, MESH: HIV Infections, Viral Load, Vaccination and Immunization, Research Design, Medical Microbiology, HIV epidemiology, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Physical Sciences, Viruses, Pathogens, MESH: Viral Load, Statistics (Mathematics), Research Article, Anti-HIV Agents, Immunology, Antiretroviral Therapy, Research and Analysis Methods, Microbiology, MESH: Cross-Sectional Studies, Antiviral Therapy, Virology, Retroviruses, Humans, MESH: Africa South of the Sahara, Statistical Methods, Microbial Pathogens, Africa South of the Sahara, MESH: Humans, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, Cross-Sectional Studies, People and Places, Africa, lcsh:Q, Preventive Medicine, Mathematics, Viral Transmission and Infection, Meta-Analysis
Abstract: International audience; Background: UNAIDS recently defined the 90-90-90 target as a way to end the HIV epidemic. However, the proportion of virological success following antiretroviral therapy (ART) may not be as high as the anticipated 90%, and may in fact be highly heterogeneous. We aimed to describe the proportion of virological success in sub-Saharan Africa and to identify factors associated with the proportion of virological success. Methods: We performed a systematic review and meta-analysis focusing on the proportion of patients in sub-Saharan Africa who demonstrate virological success at 12 and 24 months since ART initiation, as well as at 6 and 36 months, where possible. Programme factors associated with the proportion of virological success were identified using meta-regression. Analyses were conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches. Results: Eighty-five articles were included in the meta-analysis, corresponding to 125 independent study populations. Using an on-treatment approach, the proportions (95% confidence interval (CI)) of virological success at 12 (n = 64) and at 24 (n = 32) months since ART initiation were 87.7% (81.3-91.0) and 83.7% (79.8-87.6), respectively. Univariate analysis indicated that the proportion of virological success was not different by study design. Multivariate analysis at 24 months showed that the proportion of virological success was significantly larger in studies conducted in public sector sites than in other sites (p = 0.045). Using an ITT approach, the proportions (95% CI) of virological success at 12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8-69.1) and 56.8% (51.3-62.4), respectively. At 12 months, multivariate analysis showed that the proportion of success was significantly lower in cohort studies than in trials (63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that the proportion of success was also lower in cohorts. Discussion: Regardless of the time following ART initiation, and of the threshold, proportions of virological success were highly variable. Evidence from this review suggests that the new international target of 90% of patients controlled is not yet being achieved, and that in order to improve the virological outcome, efforts should be made to improve retention in care.
Published: 2016

28. Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial

Author: Bénédicte Loze, Nadia Mahjoub, Catherine Capitant, Lauriane Goldwirt, Stéphane Morel, Jean-Michel Molina, Peter L. Anderson, Allan J. Hance, Isabelle Charreau, Milad Taouk, Fabrizio Mammano, Laurence Meyer, Julien Fonsart, Sentob Saragosti, François Clavel, Constance Delaugerre, Gilles Peytavin, Lane R. Bushman, Hopital Saint-Louis [AP-HP] (AP-HP), 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), Université Paris Diderot - Paris 7 (UPD7), AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Colorado [Denver], Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), AIDES [Pantin, France], Mammano, Fabrizio, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: 0301 basic medicine, Male, Saliva, [SDV]Life Sciences [q-bio], HIV Infections, Placebos, Pre-exposure prophylaxis, 0302 clinical medicine, MESH: Tenofovir, immune system diseases, MESH: Emtricitabine, Emtricitabine, Pharmacology (medical), 030212 general & internal medicine, MESH: Anti-HIV Agents, virus diseases, MESH: HIV Infections, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, MESH: Unsafe Sex, Anti-HIV Agents, 030106 microbiology, Urology, Cmax, MESH: Placebos, 03 medical and health sciences, Pharmacokinetics, MESH: Antibiotic Prophylaxis, medicine, Humans, MESH: Saliva, Dosing, Tenofovir, Pharmacology, MESH: Humans, Unsafe Sex, business.industry, MESH: Adult, Antibiotic Prophylaxis, MESH: Male, Pharmacodynamics, Pre-Exposure Prophylaxis, business, Ex vivo, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; In the ANRS IPERGAY pre-exposure prophylaxis (PrEP) trial, a single dose of tenofovir disoproxil fumarate and emtricitabine was taken orally 2-24 h before sexual intercourse. A sub-study was conducted to assess the pharmacokinetics of tenofovir and emtricitabine in blood, saliva and rectal tissue following this initial oral intake. Methods: Plasma, PBMC, saliva and rectal tissue sampling was performed over 24 h in 12 seronegative men before enrolment in the ANRS IPERGAY trial, following a single dose of 600 mg tenofovir disoproxil fumarate/400 mg emtricitabine. Ex vivo HIV infectibility of rectal biopsies was also assessed. Results: The median plasma T max of tenofovir (median C max : 401 mg/L) and emtricitabine (median C max : 2868 mg/L) was obtained 1 h (range: 0.5-4) and 2 h (range: 1-4) after dosing, respectively. The median C 24 of tenofovir and emtricitabine was 40 and 63 mg/L, respectively. The median PBMC tenofovir diphosphate and emtricitabine triphosphate levels were 12.2 and 16.7 fmol/10 6 cells and 2800 and 2000 fmol/10 6 cells at 2 and 24 h after dosing, respectively. Saliva/plasma AUC 0-24 ratios were 2% and 17% for tenofovir and emtricitabine, respectively. Emtricitabine was detected in rectal tissue 30 min after dosing, whereas tenofovir was only detectable at 24 h. Ex vivo HIV infectibility assays of rectal biopsies showed partial protection after dosing (P,0.07). Discussion: A single high dose of oral tenofovir disoproxil fumarate/emtricitabine provides rapid and high blood levels of tenofovir and emtricitabine, with rapid diffusion of emtricitabine in saliva and rectal tissue.
Published: 2016

29. Cellular HIV-1 DNA quantification and short-term and long-term response to antiretroviral therapy

Author: Masquelier, B., Taieb, A., Reigadas, S., Marchou, B., Cheneau, C., Spire, B., Charpentier, C., Leport, C., Raffi, F., Chene, G., Descamps, D., Salamon, R., Moatti, J.- P., Pierret, J., Brun-Vezinet, F., Fleury, H., Peytavin, G., Garraffo, R., Costagliola, D., Dellamonica, P., Katlama, C., Meyer, L., Salmon, D., Sobel, A., Cuzin, L., Dupon, M., Duval, X., Le Moing, V., May, T., Morlat, P., Rabaud, C., Waldner-Combernoux, A., Reboud, P., Couffin-Cadiergues, S., Marchand, L., Bouteloup, V., Bouhnik, A. D., Brunet-Francois, C., Caron, V., Carrieri, M. P., Courcoul, M., Couturier, F., Hardel, L., Iordache, L., Kurkdji, P., Martiren, S., Preau, M., Protopopescu, C., Surzyn, J., Villes, V., Schmit, J. L., Chennebault, J. M., Faller, J. P., Mgy-Bertrand, N., Hoen, B., Drobachef, Bouchaud, O., Longy-Boursier, Ragnaud, J. M., Granier, P., Garre, M., Verdon, R., Merrien, D., Devidas, A., Piroth, L., Perronne, C., Froguel, E., Ceccaldi, J., Peyramond, D., Allard, C., Reynes, J., Fuzibet, J. G., Arsac, P., Bouvet, E., Bricaire, F., Bergmann, P., Cabane, J., Monsonego, J., Girard, P. M., Guillevin, L., Herson, S., Meyohas, M. C., Molina, J. M., Pialoux, G., Roblot, P., Jaussaud, R., Michelet, C., Lucht, F., Debord, T., Rey, D., De Jaureguiberry, J. P., Bernard, L., Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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 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), 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), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies infectieuses et tropicales, Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies Infectieuses et Tropicales, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], 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 Paris Diderot - Paris 7 (UPD7)
Subjects: Male, medicine.medical_treatment, HIV Infections, Polymerase Chain Reaction, MESH: Antiretroviral Therapy, Highly Active, Cohort Studies, MESH: Proviruses, MESH: HIV-1, chemistry.chemical_compound, Proviruses, MESH: Drug Monitoring, Antiretroviral Therapy, Highly Active, Immunopathology, Pharmacology (medical), Prospective Studies, MESH: Anti-HIV Agents, MESH: Cohort Studies, MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, biology, virus diseases, MESH: HIV Infections, Middle Aged, Viral Load, 3. Good health, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Lentivirus, Cohort, Female, Drug Monitoring, MESH: Viral Load, Viral load, Adult, Microbiology (medical), Anti-HIV Agents, Peripheral blood mononuclear cell, Virus, 03 medical and health sciences, medicine, Humans, 030304 developmental biology, Pharmacology, Chemotherapy, MESH: Humans, 030306 microbiology, MESH: Adult, MESH: Polymerase Chain Reaction, biology.organism_classification, MESH: Male, MESH: Prospective Studies, MESH: DNA, Viral, chemistry, DNA, Viral, Immunology, HIV-1, MESH: Female, DNA
Abstract: International audience; BACKGROUND: The aim of our study was to determine whether HIV-1 DNA level before antiretroviral therapy (ART) was associated with short- and long-term virological and immunological responses. METHODS: Patients starting first-line protease inhibitor-containing regimens were enrolled in a prospective multicentre cohort in 1998-99. HIV-1 DNA was quantified using real-time PCR at baseline and after 1 year of ART. The association between HIV-1 DNA and virological and immunological responses after 1 and 7 years on ART was studied in multivariate regression models along with other biological and clinical variables. Virological failure (VF) at month 12 (M12) was defined as a plasma HIV-1 RNA >500 copies/mL. Time to death or two plasma HIV-1 RNA >500 copies/mL between M12 and M84 was studied for long-term VF. RESULTS: HIV-1 DNA levels were measured in 148 patients. The median baseline peripheral blood mononuclear cell (PBMC) HIV-1 DNA was 3.7 log(10) copies/10(6) PBMCs. At M12, the median PBMC HIV-1 DNA was 2.99 log(10) copies/10(6) PBMCs. The median decrease in PBMC HIV-1 DNA between M0 and M12 was -0.7 log(10) copies/10(6) PBMCs. Higher baseline PBMC HIV-1 DNA and plasma HIV-1 RNA were independently associated with a higher risk of VF at M12. Only the baseline plasma HIV-1 RNA was independently associated with long-term virological response. The baseline CD4 cell count was the only parameter associated with short- and long-term immunological responses. CONCLUSIONS: HIV-1 DNA impacted the virological response in our cohort. Further research is warranted to study the impact of HIV-1 DNA with currently recommended first-line cART.
Published: 2011
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30. Maximum Likelihood Estimation of Long-Term HIV Dynamic Models and Antiviral Response

Author: Marc Lavielle, Adeline Samson, Ana Karina Fermin, France Mentré, Model selection in statistical learning (SELECT), Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Modélisation aléatoire de Paris X (MODAL'X), Université Paris Nanterre (UPN), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Comets, Emmanuelle
Subjects: Computer science, HIV Infections, 01 natural sciences, 010104 statistics & probability, Indinavir, Statistics, Prevalence, MESH: Anti-HIV Agents, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Treatment Outcome, Likelihood Functions, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Applied Mathematics, virus diseases, Lopinavir, MESH: HIV Infections, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Treatment Outcome, General Agricultural and Biological Sciences, Viral load, Algorithms, medicine.drug, Statistics and Probability, Mathematical optimization, Anti-HIV Agents, Differential equation, MESH: Algorithms, Stochastic approximation, Models, Biological, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, MESH: Computer Simulation, medicine, Humans, Computer Simulation, 0101 mathematics, MESH: Prevalence, 030304 developmental biology, Models, Statistical, MESH: Humans, General Immunology and Microbiology, Model selection, MESH: Models, Biological, Term (time), Nelfinavir, MESH: Likelihood Functions, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Models, Statistical
Abstract: International audience; HIV dynamics studies, based on differential equations, have significantly improved the knowledge on HIV infection. While first studies used simplified short-term dynamic models, recent works considered more complex long-term models combined with a global analysis of whole patient data based on nonlinear mixed models, increasing the accuracy of the HIV dynamic analysis. However statistical issues remain, given the complexity of the problem. We proposed to use the SAEM (stochastic approximation expectation-maximization) algorithm, a powerful maximum likelihood estimation algorithm, to analyze simultaneously the HIV viral load decrease and the CD4 increase in patients using a long-term HIV dynamic system. We applied the proposed methodology to the prospective COPHAR2-ANRS 111 trial. Very satisfactory results were obtained with a model with latent CD4 cells defined with five differential equations. One parameter was fixed, the 10 remaining parameters (eight with between-patient variability) of this model were well estimated. We showed that the efficacy of nelfinavir was reduced compared to indinavir and lopinavir.
Published: 2010

31. 5-Modified-2′-dU and 2′-dC as Mutagenic Anti HIV-1 Proliferation Agents: Synthesis and Activity

Author: Jean-Christophe Paillart, Géraldine Laumond, Roland Marquet, Alain Burger, Valérie Vivet-Boudou, Anne-Marie Aubertin, Yazan El Safadi, 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), Laboratoire de Virologie [Strasbourg], Laboratoire de Chimie des Molécules Bioactives et des Armes, Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)
Subjects: MESH: Cell Line, Tumor, Anti-HIV Agents, Cell Survival, MESH: HIV Reverse Transcriptase, Genome, Viral, Virus Replication, 01 natural sciences, MESH: Pyrimidine Nucleosides, MESH: HIV-1, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, MESH: Structure-Activity Relationship, Serial passage, Cell Line, Tumor, Drug Discovery, Humans, Structure–activity relationship, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Anti-HIV Agents, MESH: Mutagenesis, 030304 developmental biology, 0303 health sciences, MESH: Humans, 010405 organic chemistry, MESH: Virus Replication, Mutagenesis, Biological activity, Pyrimidine Nucleosides, HIV Reverse Transcriptase, In vitro, 3. Good health, 0104 chemical sciences, Aglycone, MESH: Cell Survival, chemistry, Biochemistry, Cell culture, HIV-1, Reverse Transcriptase Inhibitors, Molecular Medicine, MESH: Genome, Viral, MESH: Reverse Transcriptase Inhibitors, Nucleoside
Abstract: International audience; With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified on the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds plus two additional ones (5-carbamoyl-2'-dU (1a) and 5-carbamoylmethyl-2'-dU (1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.
Published: 2010

32. Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort

Author: Linda, Wittkop, Dominique, Breilh, Daniel, Da Silva, Pierre, Duffau, Patrick, Mercié, Isabelle, Raymond, Guerric, Anies, Hervé, Fleury, Marie-Claude, Saux, Francois, Dabis, Catherine, Fagard, Rodolphe, Thiébaut, Bernard, Masquelier, Isabelle, Pellegrin, D, Touchard, 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, Département de pharmacocinétique et pharmacologie clinique, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de médecine interne et maladies infectieuses [Bordeaux], and CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André
Subjects: Male, MESH: CD4 Lymphocyte Count, Integrase inhibitor, HIV Infections, MESH: Antiretroviral Therapy, Highly Active, Raltegravir Potassium, Cohort Studies, MESH: HIV-1, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Pharmacology (medical), 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Cohort Studies, MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Drug Resistance, Viral, MESH: HIV Infections, Middle Aged, Viral Load, Pyrrolidinones, 3. Good health, Treatment Outcome, Infectious Diseases, Cohort, Female, MESH: Viral Load, Viral load, medicine.drug, Cohort study, Adult, Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, MESH: Pyrrolidinones, Article, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, medicine, Humans, Pharmacology, MESH: Humans, 030306 microbiology, business.industry, MESH: Adult, Odds ratio, Raltegravir, MESH: Male, CD4 Lymphocyte Count, Surgery, Regimen, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; BACKGROUND: The efficacy of raltegravir plus optimized background therapy (OBT) has been demonstrated for antiretroviral (ARV)-experienced HIV-1-infected patients in randomized clinical trials. We studied viro-immunological response, pharmacokinetic parameters and genotypic test results in an observational cohort of multiple ARV class-experienced patients starting a raltegravir-based regimen. METHODS: Already enrolled ANRS CO3 Aquitaine Cohort patients with virological failure were included in this study after starting a raltegravir-based regimen (400 mg twice a day, week 0). Virological success was defined by the plasma HIV-1 RNA level [viral load (VL)] or =1 and or =2 (P = 0.02), respectively. Raltegravir-related mutations emerged in 9 of 11 failing patients (82%): Q148H/R (n = 5), N155S/H (n = 3) and S230N (n = 1). Median CD4 increases from week 0 to week 4 and week 24 were 28 (-4, 85) and 57 (0, 156) cells/mm(3), respectively. A poor immune response was independently associated with a lower VL decline (week 0 to week 12) [odds ratio (OR): 3.5, 95% confidence interval (CI): 1.4, 8.4, for 1 log(10) less] and CD4+% at baseline (OR: 2.6, 95% CI: 0.97, 8.3, for 10% lower). CONCLUSIONS: Raltegravir plus OBT provided a good virological success rate in highly pre-treated patients under clinical routine conditions.
Published: 2009

33. IL-10-secreting T cells from HIV-infected pregnant women downregulate HIV-1 replication: effect enhanced by antiretroviral treatment

Author: David Klatzmann, Michelle Rosenzwajg, Regis M. Andrade, Joana Hygino, Carmen S.M. Saramago, Renato G Silva, Ulisses C. Linhares, Rodrigo Brindeiro, Cleonice A.M. Bento, Agostinho Alves de Lima e Silva, Amilcar Tanuri, Arnaldo F.B. Andrade, Department of Medicine, Federal University of Sao Paulo, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-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)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: MESH: Interleukin-10, MESH: CD4 Lymphocyte Count, medicine.medical_treatment, HIV Infections, MESH: T-Lymphocyte Subsets, Virus Replication, MESH: Down-Regulation, MESH: HIV-1, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, T-Lymphocyte Subsets, Immunology and Allergy, MESH: Anti-HIV Agents, Pregnancy Complications, Infectious, Cells, Cultured, MESH: Cytokines, 0303 health sciences, biology, Interleukin, MESH: HIV Infections, Interleukin-10, 3. Good health, MESH: Infectious Disease Transmission, Vertical, Interleukin 10, Infectious Diseases, Cytokine, MESH: Young Adult, Lentivirus, Cytokines, Female, Tumor necrosis factor alpha, MESH: Cells, Cultured, Adult, Anti-HIV Agents, Immunology, Down-Regulation, Virus, Proinflammatory cytokine, Young Adult, 03 medical and health sciences, Immune system, MESH: Cell Proliferation, medicine, Humans, MESH: Pregnancy Complications, Infectious, Cell Proliferation, 030304 developmental biology, MESH: Humans, business.industry, MESH: Virus Replication, MESH: Adult, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Th1 Cells, biology.organism_classification, Infectious Disease Transmission, Vertical, CD4 Lymphocyte Count, MESH: Th1 Cells, HIV-1, business, MESH: Female, 030215 immunology
Abstract: International audience; OBJECTIVE: This study aimed to evaluate the impact of pregnancy-related immune events on the HIV-1 replication and to analyze their relationship with the risk of vertical transmission. METHODS: The peripheral blood from HIV-1-infected pregnant women who controlled (G1) or not controlled (G2) their plasma viral load was drawn, and the plasma and the T cells were obtained. The T-cell cultures were activated in vitro with anti-CD3 and anti-CD28, and the proliferation and cytokine production profile were evaluated after 3 days of incubation. The in-vitro HIV-1 replication was measured in culture supernatants in the seventh day following stimulation. The cytokines were also analyzed in the plasma. RESULTS: Our results demonstrated a lower T-cell proliferation and a lower interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma production in polyclonally activated T-cell cultures from G1 patients, when compared with G2. Furthermore, high levels of interleukin-10 were produced both systemically and by activated T-cell cultures from G1 patients. Interestingly, the neutralization of endogenous interleukin-10 by anti-interleukin-10 monoclonal antibody elevated both the inflammatory cytokines' release and the HIV-1 replication in the polyclonally activated T-cell cultures from G1 patients. Additionally, the maternal antiretroviral treatment significantly enhanced the systemic interleukin-10 production. Finally, the higher systemic interleukin-10 levels were inversely correlated with vertical virus transmission risk. CONCLUSION: These results indicate that a high tendency of pregnant women to produce interleukin-10 can help them control the HIV-1 replication, and this can reduce the risk of vertical transmission. Furthermore, our data suggest a role for maternal antiretroviral treatment in enhancing this phenomenon.
Published: 2009

34. High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients

Author: Clotilde Allavena, Marie-Paule Schmitt, Bruno Hoen, Pascal Chavanet, P. Meyer, Michel Duong, J. M. Lang, David Rey, M. Diemer, Thierry May, Vincent Calvez, Bruno Spire, G. Hoizey, Gilles Peytavin, J. L. Schmit, Entente Interdépartementale pour la Démoustication, Région Rhône-Alpes, Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut de Recherches sur les lois Fondamentales de l'Univers ( IRFU ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Laboratoire du Service d'Oncologie Médicale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement (UMR 6249) (LCE), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, MESH: CD4 Lymphocyte Count, HIV Infections, MESH : Viral Load, Gastroenterology, MESH: HIV-1, MESH : Adenine, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH : Female, Pharmacology (medical), 030212 general & internal medicine, MESH: Nevirapine, MESH: Anti-HIV Agents, MESH : Viral Proteins, MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Drug Resistance, Viral, Reverse-transcriptase inhibitor, MESH : Lamivudine, Lamivudine, MESH: HIV Infections, Middle Aged, Viral Load, MESH : Adult, Resistance mutation, MESH: Amino Acid Substitution, 3. Good health, MESH : Drug Resistance, Viral, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Infectious Diseases, Female, Viral disease, MESH: Viral Load, MESH : Phosphonic Acids, MESH : HIV-1, MESH: Lamivudine, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Adenine, Nevirapine, Anti-HIV Agents, MESH : Male, MESH : Nevirapine, Mutation, Missense, Organophosphonates, MESH: Phosphonic Acids, MESH : Treatment Outcome, Biology, Viral Proteins, 03 medical and health sciences, Zidovudine, MESH : Amino Acid Substitution, Internal medicine, Drug Resistance, Viral, MESH : CD4 Lymphocyte Count, MESH : HIV Infections, medicine, Humans, MESH : Middle Aged, Tenofovir, Pharmacology, MESH: Mutation, Missense, MESH: Humans, 030306 microbiology, Adenine, MESH : Anti-HIV Agents, MESH : Humans, MESH: Adult, Interim analysis, MESH: Viral Proteins, Virology, MESH: Male, CD4 Lymphocyte Count, Regimen, Amino Acid Substitution, HIV-1, MESH: Female, MESH : Mutation, Missense
Abstract: International audience; BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count
Published: 2008

35. Population pharmacokinetic analysisof lamivudine, stavudine and zidovudine in controlled HIV-infected patients on HAART

Author: Panhard, Xavière, Legrand, Mayeule, Taburet, Anne-Marie, Diquet, Bertrand, Goujard, Cécile, Mentré, France, Anrs 102 Study Group, Cophar 1, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Département de Pharmacologie-Toxicologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Comets, Emmanuelle
Subjects: Male, MESH: Drug Interactions, HIV Infections, Indinavir, Pharmacology, 030226 pharmacology & pharmacy, MESH: Antiretroviral Therapy, Highly Active, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Drug Interactions, Tissue Distribution, Pharmacology (medical), Population pharmacokinetics, MESH: Anti-HIV Agents, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Aged, Volume of distribution, 0303 health sciences, education.field_of_study, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Nelfinavir, MESH: Middle Aged, Stavudine, MESH: Zidovudine, Lamivudine, MESH: HIV Infections, General Medicine, Middle Aged, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Reverse Transcriptase Inhibitors, Nucleoside analogs, Female, Zidovudine, MESH: Lamivudine, medicine.drug, Adult, Anti-HIV Agents, MESH: Nelfinavir, Population, MESH: Stavudine, Biology, Models, Biological, Article, 03 medical and health sciences, Pharmacokinetics, medicine, Humans, Drug-drug interactions, MESH: Tissue Distribution, education, Aged, MESH: Humans, 030306 microbiology, MESH: Indinavir, MESH: Models, Biological, MESH: Adult, MESH: Male, MESH: Reverse Transcriptase Inhibitors, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female
Abstract: This work aimed at building a population pharmacokinetic (PK) model for lamivudine (LMV), stavudine (STV) and zidovudine (ZDV), estimating their inter and intraindividual PK variability and investigating the influence of different covariates. Population PK of LMV, STV and ZDV was separately evaluated from plasma concentrations obtained in 54, 39 and 27 HIV1-infected patients, respectively, enrolled in the COPHAR1-ANRS102 trial. The primary objective of this trial was to study the pharmacokinetics of indinavir (IDV) and nelfinavir (NFV) in treated patients with a sustained virological response. Concentrations of nucleoside analogs (NA) were measured in plasma as a secondary objective. A one-compartment model with first-order elimination was used, with zero-order absorption for LMV and first-order absorption for STV and ZDV. Mean parameters [interpatient variability in coefficient of variation (CV%)] of LMV, STV and ZDV were: oral volume of distribution (V/F) 145 l (52%), 24 l (81%) and 248 l (80%), oral clearance (Cl/F) 32 l/h, 16 l/h (74%) and 124 l/h (51%), respectively. For LMV, absorption duration (T a ) was 1.46 h (64%). For STV and ZDV, k a was 0.46 h−1 and 2.9 h−1, respectively. We found a systematic effect of combination with NFV vs. IDV. We found that intrapatient variability was greater than interpatient variability (except for STV) and greater than 55% for the three drugs. This trial enabled the estimation of the population PK parameters of three NA in patients with a sustained virological response, and the median curves could be used as references for concentration-controlled strategies. We observed, as for the protease inhibitors, a great variability of PK parameters.
Published: 2007

36. Potent inhibition of HIV-1 replication by backbone cyclic peptides bearing the Rev arginine rich motif

Author: Abraham Loyter, Laurence Briant, Fatima Smagulova, Christian Devaux, Elana Hariton-Gazal, Laurent Chaloin, Institut de Recherche en Infectiologie de Montpellier (IRIM), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, MESH: Protein Precursors, T-Lymphocytes, viruses, Endocrinology, Diabetes and Metabolism, Amino Acid Motifs, Clinical Biochemistry, Peptide, Virus Replication, HIV Envelope Protein gp160, MESH: HIV-1, MESH: Amino Acid Motifs, Pharmacology (medical), MESH: Anti-HIV Agents, chemistry.chemical_classification, 0303 health sciences, MESH: HIV Long Terminal Repeat, MESH: Arginine, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cyclic peptide, 3. Good health, Gene Products, rev, Biochemistry, MESH: RNA, Viral, RNA, Viral, tat Gene Products, Human Immunodeficiency Virus, MESH: Models, Molecular, Anti-HIV Agents, 030303 biophysics, Biology, Arginine, Peptides, Cyclic, 03 medical and health sciences, Viral life cycle, Humans, Protein Precursors, Binding site, Nuclear export signal, Molecular Biology, MESH: Peptides, Cyclic, HIV Long Terminal Repeat, 030304 developmental biology, MESH: tat Gene Products, Human Immunodeficiency Virus, MESH: Humans, MESH: Virus Replication, Biochemistry (medical), RNA, Cell Biology, MESH: HIV Envelope Protein gp160, MESH: Gene Products, rev, In vitro, MESH: Hela Cells, MESH: T-Lymphocytes, chemistry, HIV-1, Nuclear transport, HeLa Cells
Abstract: Due to its essential role in the virus life cycle, the viral regulatory protein Rev constitutes an attractive target for the development of new antiviral molecules. In this work, a series of Backbone Cyclic Peptide (BCP) analogs that bear a conformationally constrained arginine rich motif (ARM) of Rev were tested for in vitro inhibition of HIV-1 replication. We observed a potent suppression of HIV-1 replication in chronically infected T lymphocytic cells treated with Rev-BCPs. We further investigated possible mechanisms of HIV-1 inhibition and showed that Rev-BCPs interfere slightly with the nuclear import process and are very efficient in blocking a mechanism that controls Pr55(gag) and gp160(env) synthesis. Interestingly, these protein precursors are known to be encoded by mRNAs that require Rev-binding for nuclear export. In situ hybridization using a Cy-3 conjugated HIV-1 gag oligonucleotide probe indicated that Rev-BCPs prevent the intracellular accumulation of unspliced viral RNA. As a model, the most promising analog, Rev-BCP 14, was studied by molecular modeling and dynamics in order to identify its binding site on the Rev Response Element (RRE). The annealing simulation suggests that upon binding on the RRE, Rev-BCP 14 widens the distorted major groove of the viral RNA. Numerous contacts between peptide and RNA were found within the complex and some were identified as key components for the interactions. Altogether, our data indicate that the use of conformationally constrained Rev-BCPs represents a promising strategy for the development of new peptide-based therapeutic agents against HIV-1.
Published: 2007

37. CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Author: Geng, Elvin H, Neilands, Torsten B, Thièbaut, Rodolphe, Bwana, Mwebesa Bosco, Nash, Denis, Moore, Richard D, Wood, Robin, Zannou, Djimon Marcel, Althoff, Keri N, Lim, Poh Lian, Nachega, Jean B, Easterbrook, Philippa J, Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Ki Li, Patrick Chung, Bangsberg, David R, Fox, Matthew P, Prozesky, HansW, Hunt, Peter W, Davies, Mary-Ann, Reynolds, Steven J, Egger, Matthias, Yiannoutsos, Constantin T, Vittinghoff, Eric V, Deeks, Steven G, Martin, Jeffrey N, University of California [San Francisco] (UCSF), University of California, Université de Bordeaux (UB), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- 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), Mbarara University of Science and Technology [Mbarara] (MUST), City University of New York [New York] (CUNY), Johns Hopkins University (JHU), University of Cape Town, Centre National Hospitalier Universitaire Hubert K. Maga de Cotonou (CNHU-HKM), 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), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Infectious Disease Institute [Kampala], Makerere University [Kampala, Ouganda] (MAK), Queen Elizabeth Hospital [Hong Kong] (QEH), Massachusetts General Hospital [Boston], Boston University [Boston] (BU), Stellenbosch University, Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern], Indiana University [Bloomington], Indiana University System, Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), DARMIGNY, Sandrine, University of California [San Francisco] (UC San Francisco), University of California (UC), and Universität Bern [Bern] (UNIBE)
Subjects: Adult, Cyclopropanes, Male, Asia, MESH: CD4 Lymphocyte Count, Anti-HIV Agents, [SDV]Life Sciences [q-bio], 610 Medicine & health, HIV Infections, MESH: Africa, Virus Replication, 360 Social problems & social services, Humans, Nevirapine, MESH: Anti-HIV Agents, MESH: Nevirapine, MESH: Humans, MESH: Asia, MESH: Virus Replication, virus diseases, MESH: Adult, MESH: HIV Infections, MESH: Male, Benzoxazines, CD4 Lymphocyte Count, Miscellaneous, MESH: North America, [SDV] Life Sciences [q-bio], MESH: Drug Therapy, Combination, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Alkynes, MESH: RNA, Viral, MESH: Benzoxazines, Africa, North America, RNA, Viral, Drug Therapy, Combination, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract: BACKGROUND Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. METHODS We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level
Published: 2015

38. Poor recognition of HIV-1 Nef protein by CD8 T cells from HIV-1-infected children: Impact of age

Author: Christine Rouzioux, Florence Buseyne, Daniel Scott-Algara, Marianne Burgard, Elizabeth Monchatre, Nassima Bellal, Stéphane Blanche, Yves Rivière, Béatrice Corre, Françoise Porrot, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Immunologie Moléculaire, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunopathologie Virale, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Nef Protein, Anti-HIV Agents, viruses, Human immunodeficiency virus (HIV), HIV Infections, CD8-Positive T-Lymphocytes, Biology, medicine.disease_cause, Gene Products, nef, MESH: HIV-1, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, Cytotoxic T cell, nef Gene Products, Human Immunodeficiency Virus, HIV perinatal infection, MESH: Anti-HIV Agents, Children, Retrospective Studies, 030304 developmental biology, Dominance (genetics), MESH: Age Factors, 0303 health sciences, MESH: Humans, ELISPOT, MESH: Child, Preschool, Age Factors, Infant, HIV, virus diseases, MESH: Retrospective Studies, MESH: HIV Infections, MESH: CD8-Positive T-Lymphocytes, MESH: Infant, CTL, Elispot, Positive response, CD8 T cell, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, HIV-1, MESH: Gene Products, nef, Ex vivo, 030215 immunology
Abstract: International audience; Recognition of various HIV proteins by CD8 T cells from HIV-infected children was determined by two functional assays. First, using an Elispot assay, we show that 80% of patients recognized Gag, 77% recognized Pol, 61% recognized Env, 44% recognized Nef and 29% recognized Vif. Frequencies of Gag-, Pol-, and Env-specific IFN-gamma producing CD8 T cells were higher than frequencies of Nef and Vif-specific CD8 T cells. The poor recognition of Nef by ex vivo CD8 T cells was confirmed by CTL assays performed in HAART na? children: 25% of children had positive response against Nef versus 44, 63 and 62% for Env, Gag, and Pol, respectively. Memory Gag-specific CTL were positively correlated with age, whereas Nef-specific CTL were negatively correlated with age. The poor Nef-specific CD8 T cell response in HIV-infected children contrasts with dominance of Nef-specific responses in infected adults.
Published: 2006

39. Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery

Author: Engsig, F. N., Zangerle, R., Katsarou, O., Dabis, F., Reiss, P., Gill, J., Porter, K., Sabin, C., Riordan, A., Fatkenheuer, G., Gutierrez, F., Raffi, F., Kirk, O., Mary-Krause, M., Stephan, C., de Olalla, P. G., Guest, J., Samji, H., Castagna, A., d'Arminio Monforte, A., Skaletz-Rorowski, A., Ramos, J., Lapadula, G., Mussini, C., Force, L., Meyer, L., Lampe, F., Boufassa, F., Bucher, H. C., De Wit, S., Burkholder, G. A., Teira, R., Justice, A. C., Sterling, T. R., M. Crane, H., Gerstoft, J., Grarup, J., May, M., Chene, G., Ingle, S. M., Sterne, J., Obel, N., Burkholder, G., Justice, A., R Sterling, T., Crane, H. M., Boulle, A., Brodt, H.-R., Casabona, J., Cavassini, M., Costagliola, D., D'Arminio Monforte, A., del Amo, J., Van Sighem, A., Hans-Ulrich Haerry, D., Hogg, R., Mocroft, A., Kitahata, M., Saag, M., Williams, M., Ingle, S., Touloumi, G., Warszawski, J., Krause, M. M., Ghosn, J., Leport, C., Wit, F., Prins, M., Gibb, D., Del Amo, J., Thorne, C., Perez-Hoyos, S., Hamouda, O., Gussenheimer-Bartmeyer, B., Noguera-Julian, A., Antinori, A., Brockmeyer, N., Battegay, M., Rauch, A., Tookey, P., Miro, J. M., de Wit, S., Goetghebuer, T., Torti, C., Garrido, M., Judd, A., Conejo, P. R., Haerry, D., Weller, I., d'Arminio-Monforte, A., Colin, C., Schwimmer, C., Termote, M., Kjaer, J., Campbell, M., Raben, D., Bohlius, J., Bouteloup, V., Bucher, H., Cozzi-Lepri, A., Dorrucci, M., Egger, M., Engsig, F., Furrer, H., Lambotte, O., Lewden, C., Lodi, S., Lodwick, R., Matheron, S., Miro, J., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Reekie, J., Scherrer, A., Smit, C., Thiebaut, R., Wittkop, L., 2nd Blood Transfusion Center and Hemophilia Center, 'Laiko' General Hospital, 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), Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Observatoire des Micro et Nano Technologies (OMNT - UMS 2920), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Southern Alberta Clinic, Research Department of Infection and Population Health [London], University College of London [London] (UCL), Equipe Perception et design sonores, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), Equipe Interactions musicales temps-réel, Maladies infectieuses et tropicales, Université Pierre et Marie Curie - Paris 6 (UPMC), Institute of Biology, Neuchatel, Université de Neuchâtel (UNINE), School of Psychology, St Andrews, University of St Andrews [Scotland], Infectious Diseases, San Raffaele Scientific Institute, EA 4100, Histoire culturelle et sociale de l'art (HiCSA), Université Panthéon-Sorbonne (UP1)-Université Panthéon-Sorbonne (UP1), Laboratory of Inorganic Chemistry, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Princeton University, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Population Sciences, 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) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Paläontologisches Institut und Museum, Universität Zürich [Zürich] (UZH), Laboratory, GD Deventer, Rigshospitalet [Copenhagen], Department of Social Medicine, University of Bristol [Bristol], Department of Infectious Diseases, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), School of Psychology and Neuroscience [University of St. Andrews], Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 1 Panthéon-Sorbonne (UP1), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), 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), Universität Zürich [Zürich] = University of Zurich (UZH), Royal GD [Deventer], Copenhagen University Hospital, Copenhagen University Hospital-Copenhagen University Hospital, 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), Engsig, F. N., Zangerle, R., Katsarou, O., Dabis, F., Reiss, P., Gill, J., Porter, K., Sabin, C., Riordan, A., Fatkenheuer, G., Gutierrez, F., Raffi, F., Kirk, O., Mary-Krause, M., Stephan, C., De Olalla, P. G., Guest, J., Samji, H., Castagna, A., D'arminio Monforte, A., Skaletz-Rorowski, A., Ramos, J., Lapadula, G., Mussini, C., Force, L., Meyer, L., Lampe, F., Boufassa, F., Bucher, H. C., De Wit, S., Burkholder, G. A., Teira, R., Justice, A. C., Sterling, T. R., M. Crane, H., Gerstoft, J., Grarup, J., May, M., Chene, G., Ingle, S. M., Sterne, J., Obel, N., Engsig, F, Zangerle, R, Katsarou, O, Dabis, F, Reiss, P, Gill, J, Porter, K, Sabin, C, Riordan, A, Fatkenheuer, G, Gutierrez, F, Raffi, F, Kirk, O, Mary-Krause, M, Stephan, C, De Olalla, P, Guest, J, Samji, H, Castagna, A, D'arminio Monforte, A, Skaletz-Rorowski, A, Ramos, J, Lapadula, G, Mussini, C, Force, L, Meyer, L, Lampe, F, Boufassa, F, Bucher, H, De Wit, S, Burkholder, G, Teira, R, Justice, A, Sterling, T, M. Crane, H, Gerstoft, J, Grarup, J, May, M, Chene, G, Ingle, S, Sterne, J, Obel, N, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, and Infectious diseases
Subjects: Male, Oncology, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], HIV Infections, MESH: Logistic Models, Cohort Studies, MESH: Cause of Death, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Cause of Death, Medicine, HIV Infection, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Cohort Studies, Immunodeficiency, Cause of death, 0303 health sciences, MESH: Middle Aged, Hazard ratio, MESH: HIV Infections, Middle Aged, Viral Load, 3. Good health, Infectious Diseases, MESH: Substance-Related Disorders, HIV/AIDS, Female, MESH: Viral Load, Viral load, MESH: Heterosexuality, Human, Adult, Microbiology (medical), Cart, medicine.medical_specialty, Logistic Model, Anti-HIV Agents, Substance-Related Disorders, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Humans, sustained viral suppression, Heterosexuality, 030304 developmental biology, MESH: Humans, business.industry, Proportional hazards model, Risk Factor, Anti-HIV Agent, HIV, MESH: Adult, Substance-Related Disorder, medicine.disease, mortality, CD4 cell recovery, Confidence interval, MESH: Male, CD4 Lymphocyte Count, Logistic Models, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort Studie, business, MESH: Female
Abstract: Background. Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/μL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality.Methods. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/μL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/μL) and Cox regression to identify associations with mortality.Results. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/μL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/μL. Individuals with CD4 ≤200 cells/μL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/μL. The increased mortality was seen across different patient groups and for all causes of death.Conclusions. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/μL have substantially increased long-term mortality. © The Author 2014.
Published: 2014

40. Artificial nucleobase-amino acid conjugates: a new class of TAR RNA binding agents

Author: Jean-Patrick Joly, Maria Duca, Patrick Eldin, Laurence Briant, Guillaume Mata, Rachid Benhida, Fabien Fontaine-Vive, Institut de Chimie de Nice (ICN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Departamento de Matematicas y Computacion (Department of Mathematics and Computer Science), Universidad de La Rioja (UR), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Amino Acids, Anti-HIV Agents, Base pair, RNA-dependent RNA polymerase, HIV Infections, MESH: Base Sequence, Virus Replication, Catalysis, Cell Line, MESH: HIV-1, MESH: Gene Products, tat, Transcription (biology), MESH: RNA, Humans, Amino Acids, MESH: Anti-HIV Agents, ComputingMilieux_MISCELLANEOUS, MESH: Humans, Base Sequence, Chemistry, Organic Chemistry, MESH: Virus Replication, Cooperative binding, RNA, Nuclease protection assay, General Chemistry, MESH: Purines, MESH: HIV Infections, Non-coding RNA, 3. Good health, MESH: Cell Line, Pyrimidines, Biochemistry, Purines, RNA editing, MESH: Pyrimidines, Gene Products, tat, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, HIV-1
Abstract: International audience; The human immunodeficiency virus type-1 (HIV-1) Tat protein stimulates transcriptional elongation. Tat is involved in the transcription machinery by binding to the transactivation response region (TAR) RNA stem-loop structure, which is encoded by the 5′ leader sequence found in all HIV-1 mRNAs. Herein, we report the rational design, synthesis, and in vitro evaluation of new RNA binding agents that were conceived in order to bind strongly and selectively to the stem-loop structure of TAR RNA and, thus, inhibit the Tat/TAR interaction. We have demonstrated that the conjugation of modified nucleobases, able to interact specifically with an RNA base pair, and various amino acids allows these motifs to bind the target RNA selectively and in a cooperative manner that leads to the inhibition of viral replication in HIV-infected cells.
Published: 2014

41. Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations

Author: Thi Thu Nga Nguyen, Sylvie Rato, François Clavel, Jean-Michel Molina, Fabrizio Mammano, Constance Delaugerre, Mammano, Fabrizio, Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Microbiology (medical), integrase strand transfer inhibitors, MESH: Raltegravir Potassium, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Mutation, Missense, Integrase inhibitor, Context (language use), HIV Integrase, resistance mechanisms, Virus Replication, medicine.disease_cause, MESH: Pyrrolidinones, Virus, 03 medical and health sciences, Raltegravir Potassium, Drug Resistance, Viral, Genotype, evolution, medicine, Humans, Pharmacology (medical), MESH: Anti-HIV Agents, 030304 developmental biology, Pharmacology, 0303 health sciences, Mutation, MESH: Mutation, Missense, MESH: Drug Resistance, Viral, MESH: Humans, biology, 030306 microbiology, MESH: HIV, MESH: Virus Replication, HIV, Raltegravir, Virology, Pyrrolidinones, 3. Good health, Integrase, [SDV] Life Sciences [q-bio], Infectious Diseases, Viral replication, biology.protein, MESH: HIV Integrase, medicine.drug
Abstract: International audience; Objectives: HIV resistance to the integrase inhibitor raltegravir in treated patients is characterized by distinct resistance pathways. We hypothesize that differences in the in vivo dynamics of HIV resistance to raltegravir are due to the genetic context of the integrase present at baseline. Patients and methods: We studied four patients whose viruses evolved towards different resistance pathways. The integrase baseline sequences were inserted into a reference clone. Primary resistance mutations were then introduced and their impact on viral replication capacity (RC) and resistance was measured. Results: Patients A and B experienced emergence and persistence of mutation N155H under raltegravir therapy. In the integrase sequence from Patient A, N155H conferred potent resistance coupled with a lower impact on RC than Q148H. In Patient B, instead, selection of N155H could be explained by the dramatic loss of RC induced by the alternative Q148H mutation. In Patient C, N155H initially emerged and was later replaced by Q148H. In this integrase context, N155H resulted in higher RC but lower resistance than Q148H. In Patient D, Q148H rapidly emerged without appearance of N155H. This was the only patient for whom Q148H conferred higher RC and resistance than N155H. Conclusions: The emergence of different resistance mutations in patients was in full agreement with the impact of mutations in different baseline integrase contexts. Evolution towards different resistance genotypes is thus largely determined by the capacity of different integrase sequences present at baseline to minimize the effect of mutations on virus RC while allowing expression of resistance.
Published: 2014

42. Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury

Author: Bhaskar Saha, Mohamed Jaber, Kerren Murray, Sophie Péron, Afsaneh Gaillard, Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Polarité cellulaire, Migration et Cancer - Cell Polarity, Migration and Cancer, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), BALLION, Bérangère, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Signal Transduction, Benzylamines, Rostral migratory stream, animal diseases, [SDV]Life Sciences [q-bio], MESH: Neurons, Cyclams, Mice, 0302 clinical medicine, Cell Movement, Heterocyclic Compounds, Cortex (anatomy), MESH: Animals, MESH: Anti-HIV Agents, MESH: Cell Movement, Cerebral Cortex, Neurons, Medicine(all), 0303 health sciences, Stem Cells, Neurogenesis, General Medicine, Anatomy, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, MESH: Neuroglia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, MESH: Chemokine CXCL12, Neuroglia, MESH: Neovascularization, Physiologic, Motor cortex, Signal Transduction, Receptors, CXCR4, MESH: Heterocyclic Compounds, Anti-HIV Agents, Subventricular zone, Neovascularization, Physiologic, MESH: Stem Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Receptors, CXCR4, Lesion, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Cell Proliferation, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Progenitor cell, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, Cell Proliferation, Cell Biology, Chemokine CXCL12, MESH: Cerebral Cortex, MESH: Male, Olfactory bulb, MESH: Neurogenesis, Mice, Inbred C57BL, MESH: Astrocytes, nervous system, Astrocytes, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; The subventricular zone (SVZ) is the principal neurogenic niche present in the adult non-human mammalian brain. Neurons generated in the SVZ migrate along the rostral migratory stream to reach the olfactory bulb. Brain injuries stimulate SVZ neurogenesis and direct migration of new progenitors to the sites of injury. To date, cortical injury-induced adult SVZ neurogenesis in mice remains ambiguous and migration of neural progenitors to the site of injury has not been studied in detail. Here we report that aspiration lesion in the motor cortex induces a transient, but significant increase in the proliferation as well as neurogenesis in the SVZ. New neural progenitors migrate ectopically to the injured area with the assistance of blood vessels and reactive astrocytes. The SVZ origin of these progenitors was further confirmed using lentiviral transduction. In addition, we show that astrocyte-assisted ectopic migration is regulated by CXCR4/SDF-1 signaling pathway. Finally, upon reaching the lesion area, these progenitors differentiate mainly into glial cells and, to a lesser extent, mature neurons. These data provide a detailed account of the changes occurring in the SVZ and the cortex following lesion, and indicate the potential of the endogenous neural progenitors in cortical repair.
Published: 2013

43. Will it be possible to live without antiretroviral therapy?

Author: Françoise Barré-Sinoussi, Gianfranco Pancino, Chiraz Hamimi, Asier Sáez-Cirión, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Our studies are funded by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). G.P. is an employee of INSERM. C.H. is a PhD student funded by the Université Pierre et Marie Curie and Sidaction, and Institut Pasteur [Paris] (IP)
Subjects: CD4-Positive T-Lymphocytes, Anti-HIV Agents, Immunology, Human immunodeficiency virus (HIV), Antiretroviral Therapy, HIV Infections, medicine.disease_cause, MESH: Antiretroviral Therapy, Highly Active, 03 medical and health sciences, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Virology, medicine, Humans, Highly Active, 030212 general & internal medicine, MESH: Anti-HIV Agents, 030304 developmental biology, 0303 health sciences, MESH: Humans, Oncology (nursing), business.industry, MESH: Host-Pathogen Interactions, virus diseases, MESH: CD4-Positive T-Lymphocytes, Hematology, MESH: HIV Infections, Viral Load, Antiretroviral therapy, 3. Good health, Infectious Diseases, Oncology, Viral replication, Host-Pathogen Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, MESH: Viral Load, Viral load, Immune activation
Abstract: International audience; PURPOSE OF REVIEW:Some individuals are able to control HIV infection (either viral replication or chronic immune activation) in the absence of therapy. We will consider recent insights into the mechanisms underlying control in these patients and how this has already encouraged the search for therapeutic approaches to induce a similar HIV functional cure in other patients.RECENT FINDINGS:Spontaneous reduction of HIV viremia to undetectable levels as observed in a few HIV-infected patients is associated with an efficient HIV-specific CD8 T-cell response, the characteristics of which are now better understood. However, maintenance of such control may involve alternative mechanisms. In particular, the presence of a very small viral reservoir seems necessary, although not sufficient, to ensure HIV control in the long term. Approaches designed to limit the early establishment of these reservoirs, to eliminate infected cells, or to avoid replenishment of the reservoirs have led to HIV remission in the absence of therapy in a few cases. Alternatively, other rare patients seem to deal with HIV infection by controlling immune activation despite high levels of viremia like the natural African monkey hosts do with SIV. These observations suggest that regulation of immune activation should be considered as a serious complement to conventional therapies targeting the virus itself.SUMMARY:A better understanding of the mechanisms underlying control of HIV infection or disease in some patients has already led to successful approaches in certain individuals. However, much work is still needed to generalize these results to the global population of HIV-infected patients.
Published: 2013

44. Can the 'seek, test, treat, and retain' strategy be effective in France?

Author: Cuzin , Lise, Allavena , Clotilde, Pugliese , Pascal, Rey , David, Hoen , Bruno, Poizot-Martin , Isabelle, Cabie , André, Yazdanpanah , Yazdan, Renseigné , Non, Unité des Maladies Infectieuses et Tropicales, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-CHU de Toulouse, Service de maladies infectieuses et tropicales [Nantes], Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Service d'immuno-hématologie clinique (CISIH), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), 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], Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), 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), 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), 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), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, 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], 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Anti-HIV Agents, HIV Infections, MESH : Viral Load, 03 medical and health sciences, 0302 clinical medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH : HIV Infections, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH : France, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Humans, 030306 microbiology, business.industry, MESH : Anti-HIV Agents, MESH : Humans, MESH: HIV Infections, Viral Load, Test (assessment), MESH: France, Infectious Diseases, Risk analysis (engineering), France, MESH: Viral Load, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2013

45. Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site

Author: Pascale Coric, Serge Turcaud, Florence Souquet, Laurence Briant, Bernard Gay, Jacques Royer, Nathalie Chazal, Serge Bouaziz, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), LIttoral ENvironnement et Sociétés - UMRi 7266 (LIENSs), Centre National de la Recherche Scientifique (CNRS)-Université de La Rochelle (ULR), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Chazal, Nathalie
Subjects: Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, gag Gene Products, Human Immunodeficiency Virus, DSB, MESH: Dose-Response Relationship, Drug, MESH: HIV-1, chemistry.chemical_compound, MESH: Structure-Activity Relationship, Drug Discovery, MESH: Anti-HIV Agents, Cytotoxicity, CA-SP1 cleavage, chemistry.chemical_classification, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, MESH: Microbial Sensitivity Tests, Chemistry, General Medicine, MESH: gag Gene Products, Human Immunodeficiency Virus, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Heteronuclear single quantum coherence spectroscopy, Stereochemistry, Anti-HIV Agents, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Microbial Sensitivity Tests, MESH: Succinates, Cleavage (embryo), 03 medical and health sciences, Structure-Activity Relationship, HIV maturation inhibitor, Structure–activity relationship, Humans, 030304 developmental biology, Pharmacology, Binding Sites, MESH: Humans, Dose-Response Relationship, Drug, 030306 microbiology, Maturation inhibitor, MESH: Triterpenes, Organic Chemistry, Succinates, Betulinic acid, Triterpenes, PyBOP, HEK293 Cells, MESH: Binding Sites, HIV-1, Bevirimat
Abstract: International audience; Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction. Moreover, its low hydrosolubility makes it difficult to study its interaction with the CA-SP1 junction. We have synthesized new derivatives of bevirimat by adding different hydrophilic substituents at the C-28 position to improve their hydrosolubility and perform the structural study of a complex by NMR. Synthesis of the new derivatives, the effect of substituents at the C-28 position and their hydrosolubility are discussed. The ability of these molecules to inhibit viral infection and their cytotoxicity is assessed. Compared to the well-known bevirimat (2), one of our compounds (16) shows a higher hydrosolubility associated with a 2.5 fold increase in activity, a higher selectivity index and a better antiviral profile. Moreover, for the first time a direct interaction between a derivative of bevirimat (16) and the domain CA-SP1eNC is shown by NMR. Information from this study should allow us to decipher the mechanism by which bevirimat inhibits HIV-1 maturation and how the natural polymorphism of the spacer peptide SP1 triggers resistance to inhibitors.
Published: 2013

46. Role and evolution of viral tropism in patients with advanced HIV disease receiving intensified initial regimen in the ANRS 130 APOLLO trial

Author: S. Couffin-Cadiergues, Delphine Bonnet, C Merle de Boever, J. M. Livrozet, S. Ben Abdallah, Patrick Yeni, D. Makhloufi, N. El Alami Talbi, M. P. Drogoul, R. Dhote, Daniel Vittecoq, B. C. Phung, N. Benmakhlouf, S Ferrando, S Breaud, F Touam, G. Melica, Pierre Tattevin, Faouzi Souala, C. Augustin-Normand, S. Wassoumbou, F. Sanderson, I. Suaud, P. De Truchis, Jean-Claude Melchior, P. Guadagnin, D. Neau, S. Pavel, B. Warde, O. Taulera, J. Durant, B. Liauthaud, V. Gueripel, P. Sellier, C. Leport, J. L. Touraine, Sophie Leautez-Nainville, N. de Castro, M. A. Arthus, A. Rachline, S. Neuville, Charlotte Charpentier, Sophie Abgrall, M. Bonmarchand, E Aïssi, J. M. Ragnaud, J. F. Faucher, Pascal Pugliese, G. Le Facher, C. Bechara, François Raffi, L. Iordache, O. Derradji, Sophie Tabuteau, A. Frosch, François Bricaire, M. C. Pertusa, J. G. Fuzibet, Y. Mouton, S. Dominguez, P. Dion, I Perbost, Lorraine Letranchant, Jean-François Delfraissy, F. De Salvador, T. Kandel, V. Joly, C. Lascoux-Combe, Cécile Goujard, David Rey, Sylvie Radenne, Michel Dupon, Marc-Antoine Valantin, S. Stegman, F. Bastides, A Brunet, H. Aumaître, M. Lafaurie, V. Reliquet, Christine Katlama, H. Gros, R. Mansouri, J. Delgado, E. Rosenthal, J. Rivalain, G. Pialloux, Cédric Arvieux, David Boutoille, S. Gallien, G. Lepeu, S. Ferret, T. May, M. Parrinello, M. Bentata, Jean-François Bergmann, O. Aubry, J. M. Besnier, Christian Trepo, M. Vassalo, H. Kouadio, Olivier Lortholary, Jean-Albert Gastaut, H. Cordel, H. Dutronc, V. Rahelinirina, P. Lack, Jade Ghosn, Catherine Fagard, J. F. Dailloux, S. Boucherit, P. Honoré-Berlureau, J. M. Chennebault, T. Tahi, Yazdan Yazdanpanah, I. Louis, P. Le Bret, J. M. Estavoyer, J. J. Laurichesse, V. Rabier, I. Schlienger, O. Danne, Jean-Michel Molina, Bruno Hoen, B. Lebouché, Louis Bernard, D. Le, E. Peyrouse, I. Raymond, A. Gervais, Benoit Visseaux, L. Blum, C. Fontaine, Christine Burty, Y Quertainmont, M. Poupard, S Bouchez, J. J. Jourdain, C Cheneau, H. Castillo, Eric Billaud, J. M. Lang, André Cabié, A. Soufflet, J. M. Chapplain, O. Mounoury, B. Bonnet, D. Salmon-Ceron, P. Jouve, V. Mondain, P. Nau, I. Fournier, F. Bailly, J. M. Jacquet, N. Colin de Verdière, C Biron, P. Chiarello, D. Sereni, S. Pierre François, G. Fabre, Juliette Pavie, Lucile Larrouy, F. Rouges, Nathalie Colin de Verdiere, A. Rami, T. Lukiana, M. Maynard, P. Miailhes, J. Delaune, P. Abgueguen, A. Sobel, M. Revest, Clotilde Allavena, S. Herson, Olivier Bouchaud, M. Malet, H. Hüe, M. Iguertsira, A. Leplatois, Jean-Paul Viard, A. Simon, Pierre Dellamonica, Isabelle Poizot-Martin, J. Loison, E. Teicher, M. Lagrange, K. Koffi, E. Pichard, Diane Descamps, M. Ratajczak, Christian Michelet, Loïc Guillevin, A. Krivitzky, W. Kamouh, C. Chesnel, Laurence Slama, J. Cailhol, M. Partisani, N. Agher, Luminita Schneider, S. Boucly, Y. Levy, Laurent Boyer, Jacques Reynes, A. Diallo, M. Môle, N. Bennamar, Laurent Cotte, F. Brunel-Delmas, Philippe Morlat, V. Thoirain, A Foltzer, Laurent Hustache-Mathieu, H. Berthé, Jean-Daniel Lelièvre, C. Tramoni, P. Yeni, Philippe Van de Perre, M. Gory, C. Brunet-François, W. Rozenbaum, M. Saada, Christian Perronne, M. Medus, C. Chakvetadze, T. Huynh, C. Pintado, G. Pahlavan, J. L. Esnault, J. Clarissou, D. Radia, V. Frixon-Marin, E. Boulanger, F. Jeanblanc, P. Choutet, C Ceppi, V. Prendki, Sylvie Abel, Véronique Joly, A. Certain, G. Pichancourt, V. Beaujolais, O. Faucher, C Brochier, Diane Ponscarme, P. Fischer, Aurélie Beuscart, Hugues Melliez, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Maladies infectieuses et tropicales, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANRS 130 APOLLO Trial Study Group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Enfuvirtide, enfuvirtide, MESH: HIV Envelope Protein gp41, viruses, HIV Infections, Drug resistance, MESH: Antiretroviral Therapy, Highly Active, law.invention, MESH: HIV-1, Randomized controlled trial, law, Antiretroviral Therapy, Highly Active, Genotype, Pharmacology (medical), MESH: Anti-HIV Agents, MESH: Peptide Fragments, MESH: Evolution, Molecular, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Drug Resistance, Viral, tropism, MESH: HIV Infections, Middle Aged, HIV Envelope Protein gp41, switch, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, medicine.drug, Adult, Microbiology (medical), Adolescent, Anti-HIV Agents, Mutation, Missense, Biology, Evolution, Molecular, resistance, Young Adult, 03 medical and health sciences, HIV DNA, Drug Resistance, Viral, medicine, Humans, In patient, Tropism, Aged, 030304 developmental biology, Pharmacology, MESH: Adolescent, MESH: Mutation, Missense, MESH: Humans, 030306 microbiology, MESH: Adult, Virology, Peptide Fragments, Viral Tropism, Regimen, HIV-1, Tissue tropism, MESH: Viral Tropism
Abstract: International audience; OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.
Published: 2013

47. Dynamical models of biomarkers and clinical progression for personalized medicine: The HIV context

Author: Rodolphe Thiébaut, Daniel Commenges, Mélanie Prague, CHU Bordeaux [Bordeaux], Statistics In System biology and Translational Medicine (SISTM), 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)-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)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Prague, Mélanie, 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) - 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) - Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria) - Institut National de Recherche en Informatique et en Automatique (Inria), Thiébaut, Rodolphe, and 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)
Subjects: Human immunodeficiency virus (HIV), Pharmaceutical Science, HIV Infections, Bioinformatics, medicine.disease_cause, 01 natural sciences, 010104 statistics & probability, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Precision Medicine, MESH: Anti-HIV Agents, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Treatment Outcome, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Mechanistic models, MESH: HIV Infections, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Treatment Outcome, Risk analysis (engineering), [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Host (network), Anti-HIV Agents, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], [MATH.MATH-DS] Mathematics [math]/Dynamical Systems [math.DS], Context (language use), Models, Biological, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, medicine, Humans, 0101 mathematics, Adaptation (computer science), MESH: Individualized Medicine, 030304 developmental biology, MESH: Humans, business.industry, MESH: Biological Markers, MESH: Models, Biological, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, HIV infection, Personalized medicine, Clinical trial, Dynamic models, Action (philosophy), [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, Clinical progression, Biomarkers
Abstract: International audience; Mechanistic models, based on ordinary differential equation systems, can exhibit very good predictive abilities that will be useful to build treatment monitoring strategies. In this review, we present the potential and the limitations of such models for guiding treatment (monitoring and optimizing) in HIV-infected patients. In the context of antiretroviral therapy, several biological processes should be considered in addition to the interaction between viruses and the host immune system: the mechanisms of action of the drugs, their phar-macokinetics and pharmacodynamics, as well as the viral and host characteristics. Another important aspect to take into account is clinical progression, although its implementation in such modelling approaches is not easy. Finally, the control theory and the use of intrinsic properties of mechanistic models make them very relevant for dynamic treatment adaptation. Their implementation would nevertheless require their evaluation through clinical trials.
Published: 2013

48. Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia

Author: Laurent Ferradini, Yoann Madec, Janin Nouhin, Nicole Ngo-Giang-Huong, Eric Nerrienet, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University [Cambridge]-Chiang Mai University (CMU), Institut de Recherche pour le Développement (IRD), Auteur indépendant, Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Harvard University-Chiang Mai University (CMU), Chiang Mai University (CMU), Harvard School of Public Health, Régulation des Infections Rétrovirales, and Institut Pasteur [Paris] (IP)
Subjects: Male, Drug resistance, MESH: Base Sequence, medicine.disease_cause, MESH: HIV-1, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, MESH: Drug Resistance, Multiple, Viral, 030212 general & internal medicine, MESH: Anti-HIV Agents, Child, 0303 health sciences, Mutation, Multidisciplinary, Reverse-transcriptase inhibitor, Stavudine, MESH: Zidovudine, MESH: Follow-Up Studies, MESH: Amino Acid Substitution, HIV Reverse Transcriptase, 3. Good health, Child, Preschool, Medicine, Female, Cambodia, Zidovudine, Viral load, Research Article, medicine.drug, Adult, Adolescent, MESH: HIV Reverse Transcriptase, Anti-HIV Agents, Science, Molecular Sequence Data, Mutation, Missense, MESH: Stavudine, Biology, 03 medical and health sciences, Drug Resistance, Multiple, Viral, medicine, Humans, Genotyping, Retrospective Studies, MESH: Acquired Immunodeficiency Syndrome, MESH: Adolescent, MESH: Mutation, Missense, Acquired Immunodeficiency Syndrome, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, 030306 microbiology, MESH: Cambodia, MESH: Child, Preschool, MESH: Retrospective Studies, MESH: Adult, Virology, MESH: Male, Reverse transcriptase, Amino Acid Substitution, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, Follow-Up Studies
Abstract: International audience; Background: Multi-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(t)ide reverse transcriptase inhibitors (NRTI). The presence of these mutations is an emerging problem compromising non-nucleoside reverse transcriptase inhibitors and protease inhibitors-based therapies. Furthermore, factors associated with selection of these mutations are still not well defined. The current study aimed to evaluate the frequency and to characterize factors associated with the occurrence of multi-nucleos(t)ide resistance mutations among HIV-1 infected patients failing recommended first-line antiretroviral regimens in Cambodia.Methodology/Principal Finding: This is a retrospective analysis of HIV-1 drug resistance genotyping of 520 HIV-1 infected patients in virological failure (viral load > 250 copies/mL) while on first-line antiretroviral therapy in Cambodia with at least one reverse transcriptase inhibitor resistance associated mutation. Among these 520 patients, a total of 66 subjects (66/520, 12.7%) presented ≥1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients, respectively. In multivariate analysis, both Q151M (p = 0.039) and K65R (p = 0.029) mutations were independently associated with current stavudine- compared to zidovudine-use.Conclusion: Such selection of mutations by stavudine drastically limits the choice of antiretroviral molecules available for second-line therapy in resource-limited settings. This finding supports the World Health Organization’s recommendation for stavudine phase-out.
Published: 2013

49. Continuous versus intermittent treatment strategies during primary HIV-1 infection: the randomized ANRS INTERPRIM Trial

Author: Goujard, Cécile, Emilie, Dominique, Roussillon, Caroline, Godot, Véronique, Rouzioux, Chrisitine, Venet, Alain, Colin, Céline, Pialoux, Gilles, Girard, Pierre-Marie, Boilet, Valérie, Chaix, Marie-Laure, Galanaud, Pierre, Chene, Geneviève, Michelet, Christian, Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), 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), Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-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), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Régulation de la réponse immune, infection VIH-1 et autoimmunité, 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), 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), Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), French National Agency forResearch on AIDS and ViralHepatitis (ANRS), ANRS-112 INTERPRIM Study Group, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -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 ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service des maladies infectieuses et tropicales, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA )
Subjects: CD4-Positive T-Lymphocytes, Male, antiretroviral treatment, MESH : Viral Load, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Polyethylene Glycols, MESH: HIV-1, MESH: Recombinant Proteins, 0302 clinical medicine, Pegylated interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Medicine, MESH : Female, MESH : DNA, Viral, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH: Treatment Outcome, Response rate (survey), 0303 health sciences, MESH: Middle Aged, MESH : Acquired Immunodeficiency Syndrome, treatment interruption, MESH : Polyethylene Glycols, virus diseases, MESH: CD4-Positive T-Lymphocytes, interferon, MESH: Follow-Up Studies, Middle Aged, Viral Load, MESH : Adult, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, Recombinant Proteins, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Infectious Diseases, MESH : CD4-Positive T-Lymphocytes, primary infection, MESH : Interferon-alpha, Female, MESH: Interferon-alpha, MESH: Viral Load, Viral load, MESH : HIV-1, medicine.drug, Adult, Cart, medicine.medical_specialty, Anti-HIV Agents, MESH : Recombinant Proteins, MESH : Male, MESH : Drug Administration Schedule, Immunology, CD4-CD8 Ratio, Alpha interferon, MESH : Treatment Outcome, Interferon alpha-2, MESH: Drug Administration Schedule, Drug Administration Schedule, 03 medical and health sciences, Immune system, Internal medicine, Antiretroviral treatment, Humans, MESH : Middle Aged, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH: Acquired Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome, MESH: Humans, business.industry, MESH : Anti-HIV Agents, MESH : Humans, Interferon-alpha, MESH : Follow-Up Studies, MESH: Adult, MESH: Male, Surgery, MESH: DNA, Viral, MESH: Polyethylene Glycols, MESH : CD4-CD8 Ratio, DNA, Viral, HIV-1, MESH: CD4-CD8 Ratio, business, MESH: Female, CD8, Follow-Up Studies
Abstract: International audience; OBJECTIVES: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI). DESIGN AND METHODS: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption. RESULTS: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups. CONCLUSION: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.
Published: 2012

50. [Kidney and HIV infection]

Author: Plaisier, Emmanuelle, Lescure, François-Xavier, Ronco, Pierre, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), RONCO, Pierre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: MESH: Kidney Diseases, MESH: Adenine, MESH: Humans, urogenital system, MESH: Virus Replication, MESH: Genetic Predisposition to Disease, virus diseases, MESH: Kidney, MESH: Receptor, Epidermal Growth Factor, urologic and male genital diseases, female genital diseases and pregnancy complications, MESH: Male, MESH: HIV-1, MESH: Biopsy, MESH: Glomerular Filtration Rate, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: African Continental Ancestry Group, MESH: Anti-HIV Agents, MESH: Phosphorus, MESH: AIDS-Associated Nephropathy, MESH: Organophosphonates, MESH: Female
Abstract: International audience; Screening of chronic kidney disease (CKD) that includes estimation of the glomerular filtration rate (GFR) and evaluation proteinuria should be performed in all HIV-infected patients and these parameters have to be monitored annually in patients at higher risk for CKD. Black patients have a genetic predisposition to develop HIV-associated nephropathy. Suppression of HIV viral replication with antiretroviral therapy prevents the development of HIV-associated nephropathy or halts its progression. Kidney biopsy remains the most informative diagnosis test to differentiate various forms of kidney diseases in HIV-infected patients. Dosing antiretroviral agents with kidney metabolism should be adjusted when eGFR is bellow 50 mL/min/1.73 m(2). eGFR and serum phosphorus at baseline and during treatment should be carefully assessed in patients receiving tenofovir. Proximal renal tubular toxicity must be further evaluated in the presence of eGFR decrease and/or hypophosphatemia under tenofovir therapy.
Published: 2012

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