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1. 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
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2. No increased risk of Kaposi sarcoma relapse in patients with controlled HIV‐1 infection after switching protease inhibitor‐based antiretroviral therapy

Author

Lajaunie, Rébecca, Cuzin, Lise, Palich, Romain, Makinson, Alain, Bani-Sadr, Firouzé, Duvivier, Claudine, Arvieux, Cedric, Rey, David, Poizot-Martin, Isabelle, Delpierre, Cyril, Delobel, Pierre, Martin-Blondel, Guillaume, Chirouze, C., Drobacheff-Thiébaut, C., Foltzer, A., Bouiller, K., Hustache- Mathieu, L., Lepiller, Q., Bozon, F., Babre, O, Brunel, As., Muret, P., Chevalier, E., Jacomet, C., Laurichesse, H., Lesens, O., Vidal, M., Mrozek, N., Aumeran, C., Baud, O., Corbin, V., Goncalvez, E., Mirand, A, Brebion, A, Henquell, C, Lamaury, I., Fabre, I., Curlier, E., Ouissa, R., Herrmann-Storck, C., Tressieres, B., Receveur, Mc., Boulard, F., Daniel, C., Clavel, C., Roger, Pm., Markowicz, S., Chellum Rungen, N., Merrien, D., Perré, P., Guimard, T., Bollangier, O., Leautez, S., Morrier, M., Laine, L., Boucher, D., Point, P., Cotte, L., Ader, F., Becker, A., Boibieux, A., Brochier, C., Brunel-Dalmas, F., Cannesson, O., Chiarello, P., Chidiac, C., Degroodt, S., Ferry, T., Godinot, M., Livrozet, J.M., Makhloufi, D., Miailhes, P., Perpoint, T., Perry, M., Pouderoux, C., Roux, S., Triffault-Fillit, C., Valour, F., Charre, C., Icard, V., Tardy, J.C., Trabaud, M.A., Ravaux, I., Ménard, A., Belkhir, Ay., Colson, P., Dhiver, C., Madrid, A., Martin-Degioanni, M., Meddeb, L., Mokhtari, M., Motte, A., Raoux, A., Toméi, C., Tissot-Dupont, H., Poizot-Martin, I., Brégigeon, S., Zaegel-Faucher, O., Obry-Roguet, V., Laroche, H, Orticoni, M., Soavi, M.J., Ressiot, E., Ducassou, M.J., Jaquet, I., Galie, S., Colson, H., Ritleng, A.S., Ivanova, A., Debreux, C., Lions, C., Rojas-Rojas, T, Cabié, A., Abel, S., Bavay, J., Bigeard, B., Cabras, O., Cuzin, L., Dupin de Majoubert, R., Fagour, L., Guitteaud, K., Marquise, A., Najioullah, F., Pierre-François, S., Pasquier, J., Richard, P., Rome, K., Turmel, Jm, Varache, C., Atoui, N., Bistoquet, M., Delaporte, E, Le Moing, V., Makinson, A., Meftah, N., Merle de Boever, C., Montes, B., Montoya Ferrer, A., Tuaillon, E., Reynes, J., Lefèvre, B., Jeanmaire, E., Hénard, S., Frentiu, E., Charmillon, A., Legoff, A., Tissot, N., André, M., Boyer, L., Bouillon, Mp., Delestan, M., Goehringer, F., Bevilacqua, S., Rabaud, C., May, T., Raffi, F., Allavena, C., Aubry, O., Billaud, E., Biron, C., Bonnet, B., Bouchez, S., Boutoille, D., Brunet-Cartier, C., Deschanvres, C., Gaborit, B.J., Grégoire, A., Grégoire, M., Grossi, O., Guéry, R., Jovelin, T., Lefebvre, M., Le Turnier, P., Lecomte, R., Morineau, P., Reliquet, V., Sécher, S., Cavellec, M., Paredes, E., Soria, A., Ferré, V., André-Garnier, E., Rodallec, A., Pugliese, P., Breaud, S., Ceppi, C., Chirio, D., Cua, E., Dellamonica, P., Demonchy, E., de Monte, A., Durant, J., Etienne, C., Ferrando, S., Garraffo, R., Michelangeli, C., Mondain, V., Naqvi, A., Oran, N., Perbost, I., Carles, M., Klotz, C., Maka, A., Pradier, C., Prouvost-Keller, B., Risso, K., Rio, V., Rosenthal, E., Touitou, I., Wehrlen-Pugliese, S., Zouzou, G., Hocqueloux, L., Prazuck, T., Gubavu, C., Sève, A., Giaché, S., Rzepecki, V., Colin, M., Boulard, C., Thomas, G., Cheret, A., Goujard, C., Quertainmont, Y., Teicher, E., Lerolle, N., Jaureguiberry, S., Colarino, R., Deradji, O., Castro, A., Barrail-Tran, A., Yazdanpanah, Y., Landman, R., Joly, V., Ghosn, J., Rioux, C., Lariven, S., Gervais, A., Lescure, Fx., Matheron, S., Louni, F., Julia, Z., Le Gac, S., Charpentier, C., Descamps, D., Peytavin, G., Duvivier, C., Aguilar, C., Alby-Laurent, F., Amazzough, K., Benabdelmoumen, G., Bossi, P., Cessot, G., Charlier, C., Consigny, P.H., Jidar, K., Lafont, E., Lanternier, F., Leporrier, J., Lortholary, O., Louisin, C., Lourenco, J., Parize, P., Pilmis, B., Rouzaud, C., Touam, F., Valantin, Ma., Tubiana, R., Agher, R., Seang, Sophie, Schneider, L., Palich, R., Blanc, C., Katlama, C., Bani-Sadr, F., Berger, Jl., N’guyen, Y., Lambert, D., Kmiec, I., Hentzien, M., Brunet, A., Romaru, J., Marty, H., Brodard, V., Arvieux, C., Tattevin, P., Revest, M., Souala, F., Baldeyrou, M., Patrat-Delon, S., Chapplain, J.M., Benezit, F., Dupont, M., Poinot, M., Maillard, A., Pronier, C., Lemaitre, F., Morlat, C., Poisson-Vannier, M., Sinteff, Jp., Gagneux-Brunon, A., Botelho-Nevers, E., Frésard, A., Ronat, V., Lucht, F., Rey, D., Fischer, P., Partisani, M., Cheneau, C., Priester, M., Batard, Ml., Mélounou, C, Bernard-Henry, C., de Mautort, E., Fafi-Kremer, S., Delobel, P., Alvarez, M., Biezunski, N., Debard, A., Delpierre, C., Gaube, G., Lansalot, P., Lelièvre, L., Marcel, M., Martin-Blondel, G., Piffaut, M., Porte, L., Saune, K., Robineau, O., Ajana, F., Aïssi, E., Alcaraz, I., Alidjinou, E., Baclet, V., Bocket, L., Boucher, A., Digumber, M., Huleux, T., Lafon-Desmurs, B., Meybeck, A., Pradier, M., Tetart, M., Thill, P., Viget, N., Valette, M., 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), CHU de la Martinique [Fort de France], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], CHU Strasbourg, 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), Université Toulouse III Paul Sabatier - Faculté de médecine Purpan (UTPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), And The Dat’AIDS study group: C Chirouze, C Drobacheff-Thiébaut, A Foltzer, K Bouiller, L Hustache-Mathieu, Q Lepiller, F Bozon, O Babre, A S Brunel, P Muret, E Chevalier, C Jacomet, H Laurichesse, O Lesens, M Vidal, N Mrozek, C Aumeran, O Baud, V Corbin, E Goncalvez, A Mirand, A Brebion, C Henquell, I Lamaury, I Fabre, E Curlier, R Ouissa, C Herrmann-Storck, B Tressieres, M C Receveur, F Boulard, C Daniel, C Clavel, P M Roger, S Markowicz, N Chellum Rungen, D Merrien, P Perré, T Guimard, O Bollangier, S Leautez, M Morrier, L Laine, D Boucher, P Point, L Cotte, F Ader, A Becker, A Boibieux, C Brochier, F Brunel-Dalmas, O Cannesson, P Chiarello, C Chidiac, S Degroodt, T Ferry, M Godinot, J M Livrozet, D Makhloufi, P Miailhes, T Perpoint, M Perry, C Pouderoux, S Roux, C Triffault-Fillit, F Valour, C Charre, V Icard, J C Tardy, M A Trabaud, I Ravaux, A Ménard, A Y Belkhir, P Colson, C Dhiver, A Madrid, M Martin-Degioanni, L Meddeb, M Mokhtari, A Motte, A Raoux, C Toméi, H Tissot-Dupont, I Poizot-Martin, S Brégigeon, O Zaegel-Faucher, V Obry-Roguet, H Laroche, M Orticoni, M J Soavi, E Ressiot, M J Ducassou, I Jaquet, S Galie, H Colson, A S Ritleng, A Ivanova, C Debreux, C Lions, T Rojas-Rojas, A Cabié, S Abel, J Bavay, B Bigeard, O Cabras, L Cuzin, R Dupin de Majoubert, L Fagour, K Guitteaud, A Marquise, F Najioullah, S Pierre-François, J Pasquier, P Richard, K Rome, J M Turmel, C Varache, N Atoui, M Bistoquet, E Delaporte, V Le Moing, A Makinson, N Meftah, C Merle de Boever, B Montes, A Montoya Ferrer, E Tuaillon, J Reynes, B Lefèvre, E Jeanmaire, S Hénard, E Frentiu, A Charmillon, A Legoff, N Tissot, M André, L Boyer, M P Bouillon, M Delestan, F Goehringer, S Bevilacqua, C Rabaud, T May, F Raffi, C Allavena, O Aubry, E Billaud, C Biron, B Bonnet, S Bouchez, D Boutoille, C Brunet-Cartier, C Deschanvres, B J Gaborit, A Grégoire, M Grégoire, O Grossi, R Guéry, T Jovelin, M Lefebvre, P Le Turnier, R Lecomte, P Morineau, V Reliquet, S Sécher, M Cavellec, E Paredes, A Soria, V Ferré, E André-Garnier, A Rodallec, P Pugliese, S Breaud, C Ceppi, D Chirio, E Cua, P Dellamonica, E Demonchy, A De Monte, J Durant, C Etienne, S Ferrando, R Garraffo, C Michelangeli, V Mondain, A Naqvi, N Oran, I Perbost, M Carles, C Klotz, A Maka, C Pradier, B Prouvost-Keller, K Risso, V Rio, E Rosenthal, I Touitou, S Wehrlen-Pugliese, G Zouzou, L Hocqueloux, T Prazuck, C Gubavu, A Sève, S Giaché, V Rzepecki, M Colin, C Boulard, G Thomas, A Cheret, C Goujard, Y Quertainmont, E Teicher, N Lerolle, S Jaureguiberry, R Colarino, O Deradji, A Castro, A Barrail-Tran, Y Yazdanpanah, R Landman, V Joly, J Ghosn, C Rioux, S Lariven, A Gervais, F X Lescure, S Matheron, F Louni, Z Julia, S Le Gac, C Charpentier, D Descamps, G Peytavin, C Duvivier, C Aguilar, F Alby-Laurent, K Amazzough, G Benabdelmoumen, P Bossi, G Cessot, C Charlier, P H Consigny, K Jidar, E Lafont, F Lanternier, J Leporrier, O Lortholary, C Louisin, J Lourenco, P Parize, B Pilmis, C Rouzaud, F Touam, M A Valantin, R Tubiana, R Agher, S Seang, L Schneider, R Palich, C Blanc, C Katlama, F Bani-Sadr, J L Berger, Y N'Guyen, D Lambert, I Kmiec, M Hentzien, A Brunet, J Romaru, H Marty, V Brodard, C Arvieux, P Tattevin, M Revest, F Souala, M Baldeyrou, S Patrat-Delon, J M Chapplain, F Benezit, M Dupont, M Poinot, A Maillard, C Pronier, F Lemaitre, C Morlat, M Poisson-Vannier, T Jovelin, J P Sinteff, A Gagneux-Brunon, E Botelho-Nevers, A Frésard, V Ronat, F Lucht, D Rey, P Fischer, M Partisani, C Cheneau, M Priester, M L Batard, C Mélounou, C Bernard-Henry, E de Mautort, S Fafi-Kremer, P Delobel, M Alvarez, N Biezunski, A Debard, C Delpierre, G Gaube, P Lansalot, L Lelièvre, M Marcel, G Martin-Blondel, M Piffaut, L Porte, K Saune, O Robineau, F Ajana, E Aïssi, I Alcaraz, E Alidjinou, V Baclet, L Bocket, A Boucher, M Digumber, T Huleux, B Lafon-Desmurs, A Meybeck, M Pradier, M Tetart, P Thill, N Viget, M Valette, Malbec, Odile, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Rennes (CHU Rennes), Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut des sciences de la santé publique [Marseille] (ISSPAM), European Infective Endocarditis Registry (Euro-Endo), EMERGEN consortium, Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp] (THERAVIR), 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), Laboratoire Microorganismes : Génome et Environnement (LMGE), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)

Subjects
medicine.medical_specialty, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], antiretroviral therapy, Human immunodeficiency virus (HIV), protease inhibitors, HIV Infections, medicine.disease_cause, MESH: HIV-1, Acquired immunodeficiency syndrome (AIDS), MESH: Neoplasm Recurrence, Local / complications, Internal medicine, medicine, Humans, HHV8, MESH: HIV Infections* / complications, MESH: Protease Inhibitors / adverse effects, Pharmacology (medical), Protease inhibitor (pharmacology), Sarcoma, Kaposi, Retrospective Studies, MESH: Humans, business.industry, Health Policy, Kaposi sarcoma, MESH: Retrospective Studies, Viral Load, MESH: HIV Infections* / drug therapy, medicine.disease, Antiretroviral therapy, switch, CD4 Lymphocyte Count, AIDS, [SDV] Life Sciences [q-bio], Regimen, Infectious Diseases, Increased risk, MESH: Sarcoma, Kaposi* / drug therapy, HIV-1, Sarcoma, Neoplasm Recurrence, Local, business, MESH: Viral Load, Viral load
Abstract

International audience; Objectives: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication.Methods: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen.Results: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225-560) for switching patients, compared with 362 and 136 cells/μL for the other two patients.Conclusions: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

Published
2022
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3. Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination.

Author

Durier C, Ninove L, van der Werf S, Lefebvre M, Desaint C, Bauer R, Attia M, Lecompte AS, Lachatre M, Maakaroun-Vermesse Z, Nicolas JF, Verdon R, Kiladjian JJ, Loubet P, Schmidt-Mutter C, Corbin V, Ansart S, Melica G, Resch M, Netzer E, Kherabi Y, Tardieu R, Lelièvre JD, Tartour E, Meyer L, de Lamballerie X, and Launay O

Subjects
Humans, Middle Aged, Adult, Aged, Male, Female, Incidence, Young Adult, Antibodies, Viral blood, Adolescent, Case-Control Studies, Breakthrough Infections, COVID-19 prevention & control, COVID-19 immunology, COVID-19 epidemiology, SARS-CoV-2 immunology, BNT162 Vaccine immunology, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Immunization, Secondary, Vaccination methods, Antibodies, Neutralizing blood
Abstract

Objectives: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination., Methods: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves., Results: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection., Conclusion: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Published
2024
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4. Comparing ethanol lock therapy versus vancomycin lock in a salvation strategy for totally implantable vascular access device infections due to coagulase-negative staphylococci (the ETHALOCK study): a prospective double-blind randomized clinical trial.

Author

Lesens O, Forestier E, Botelho-Nevers E, Pavese P, David G, Nougarede B, Corbin V, Pereira B, Aumeran C, and Sauvat L

Subjects
Humans, Vancomycin therapeutic use, Ethanol adverse effects, Coagulase, Prospective Studies, Staphylococcus, Catheterization, Central Venous, Superinfection complications, Catheter-Related Infections microbiology, Central Venous Catheters adverse effects, Bacteremia microbiology
Abstract

Objectives: Little is known about efficacy and safety of ethanol lock therapy (ELT) to treat totally implantable venous access device (TIVAD) infections. The objective of this trial was to evaluate the effectiveness and safety profile of a local treatment with ELT without removal for TIVAD infection due to coagulase-negative staphylococci., Methods: We performed a prospective, multicenter, double-blind, randomized clinical trial comparing the efficacy of 40% ELT versus vancomycin lock therapy (VLT) in TIVAD infections due to coagulase-negative staphylococci, complicated or not by bloodstream infection., Results: Thirty-one patients were assigned to the ELT group and 30 to the VLT arm. Concomitant bacteremia was present in 41 patients (67.2%). Treatment success was 58.1 % (18 of 31) for the ELT arm and 46.7% (14 of 30) for the VLT arm (p = 0.37). The overall treatment success was 52.5% (32). The risk of treatment failure due to uncontrolled infections, superinfections, and mechanical complications did not differ significantly between participants receiving ELT (13 out of 31 [42%]) and those receiving VLT (16 out of 30 [53%]) with a hazard ratio of 0.70 (p = 0.343; 95% CI [0.34-1.46], Cox model). Catheter malfunctions were significantly more frequent in the ELT arm (11 patients versus 2 in the VLT group, p = 0.01)., Conclusions: We found an overall high rate of treatment failure that did not differ between the ELT arm and the VLT arm. TIVAD removal must be prioritized to prevent complications (uncontrolled infections, superinfections, and catheter malfunctions) except in exceptional situations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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5. Vaccination coverage reinforced by an infectious disease consultation during pretransplant check-up in patients awaiting kidney transplantation: A randomized study.

Author

Calmels A, Heng AE, Corbin V, Garrouste C, Greze C, Pereira B, and Lesens O

Abstract

Background: Vaccine coverage (VC) in patients awaiting kidney transplantation is insufficient., Methods: We performed a prospective, single-center, interventional, randomized, open-label study comparing a reinforced group (infectious disease consultation proposed) and a standard group (letter stating vaccine recommendations sent to the nephrologist) of patients in our institution awaiting renal transplantation., Findings: Out of the 58 eligible patients, 19 declined to participate. Twenty patients were randomized to the standard group and 19 to the reinforced group. Essential VC increased from. 10% to 20% in the standard group and from 15.8% to 52.6% in the reinforced group (p < 0.034). The main obstacles identified were lack of vaccination traceability, refusal of an additional consultation and the journey time between home and hospital., Conclusion: While introduction of an infectious disease consultation during the pre-transplant check-up significantly improved VC in patients, it is time-consuming and failed to achieve a satisfactory rate of VC., Competing Interests: Declaration of Competing Interest There are no competing interests related to this work., (Copyright © 2023. Published by Elsevier Masson SAS.)

Published
2023
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6. SARS-CoV-2 mouse adaptation selects virulence mutations that cause TNF-driven age-dependent severe disease with human correlates.

Author

Bader SM, Cooney JP, Sheerin D, Taiaroa G, Harty L, Davidson KC, Mackiewicz L, Dayton M, Wilcox S, Whitehead L, Rogers KL, Georgy SR, Coussens AK, Grimley SL, Corbin V, Pitt M, Coin L, Pickering R, Thomas M, Allison CC, McAuley J, Purcell DFJ, Doerflinger M, and Pellegrini M

Subjects
Young Adult, Humans, Mice, Animals, Aged, Virulence genetics, Mutation, Disease Models, Animal, SARS-CoV-2 genetics, COVID-19 genetics
Abstract

The diversity of COVID-19 disease in otherwise healthy people, from seemingly asymptomatic infection to severe life-threatening disease, is not clearly understood. We passaged a naturally occurring near-ancestral SARS-CoV-2 variant, capable of infecting wild-type mice, and identified viral genomic mutations coinciding with the acquisition of severe disease in young adult mice and lethality in aged animals. Transcriptomic analysis of lung tissues from mice with severe disease elucidated a host antiviral response dominated mainly by interferon and IL-6 pathway activation in young mice, while in aged animals, a fatal outcome was dominated by TNF and TGF-β signaling. Congruent with our pathway analysis, we showed that young TNF-deficient mice had mild disease compared to controls and aged TNF-deficient animals were more likely to survive infection. Emerging clinical correlates of disease are consistent with our preclinical studies, and our model may provide value in defining aberrant host responses that are causative of severe COVID-19.

Published
2023
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7. Exploring convolutional neural networks with transfer learning for diagnosing Lyme disease from skin lesion images.

Author

Hossain SI, de Goër de Herve J, Hassan MS, Martineau D, Petrosyan E, Corbin V, Beytout J, Lebert I, Durand J, Carravieri I, Brun-Jacob A, Frey-Klett P, Baux E, Cazorla C, Eldin C, Hansmann Y, Patrat-Delon S, Prazuck T, Raffetin A, Tattevin P, Vourc'h G, Lesens O, and Nguifo EM

Subjects
France, Humans, Machine Learning, Neural Networks, Computer, Lyme Disease diagnosis, Skin Diseases
Abstract

Background and Objective: Lyme disease which is one of the most common infectious vector-borne diseases manifests itself in most cases with erythema migrans (EM) skin lesions. Recent studies show that convolutional neural networks (CNNs) perform well to identify skin lesions from images. Lightweight CNN based pre-scanner applications for resource-constrained mobile devices can help users with early diagnosis of Lyme disease and prevent the transition to a severe late form thanks to appropriate antibiotic therapy. Also, resource-intensive CNN based robust computer applications can assist non-expert practitioners with an accurate diagnosis. The main objective of this study is to extensively analyze the effectiveness of CNNs for diagnosing Lyme disease from images and to find out the best CNN architectures considering resource constraints., Methods: First, we created an EM dataset with the help of expert dermatologists from Clermont-Ferrand University Hospital Center of France. Second, we benchmarked this dataset for twenty-three CNN architectures customized from VGG, ResNet, DenseNet, MobileNet, Xception, NASNet, and EfficientNet architectures in terms of predictive performance, computational complexity, and statistical significance. Third, to improve the performance of the CNNs, we used custom transfer learning from ImageNet pre-trained models as well as pre-trained the CNNs with the skin lesion dataset HAM10000. Fourth, for model explainability, we utilized Gradient-weighted Class Activation Mapping to visualize the regions of input that are significant to the CNNs for making predictions. Fifth, we provided guidelines for model selection based on predictive performance and computational complexity., Results: Customized ResNet50 architecture gave the best classification accuracy of 84.42% ±1.36, AUC of 0.9189±0.0115, precision of 83.1%±2.49, sensitivity of 87.93%±1.47, and specificity of 80.65%±3.59. A lightweight model customized from EfficientNetB0 also performed well with an accuracy of 83.13%±1.2, AUC of 0.9094±0.0129, precision of 82.83%±1.75, sensitivity of 85.21% ±3.91, and specificity of 80.89%±2.95. All the trained models are publicly available at https://dappem.limos.fr/download.html, which can be used by others for transfer learning and building pre-scanners for Lyme disease., Conclusion: Our study confirmed the effectiveness of even some lightweight CNNs for building Lyme disease pre-scanner mobile applications to assist people with an initial self-assessment and referring them to expert dermatologist for further diagnosis., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2022
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