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