2021•Journal of Antimicrobial ChemotherapyRequires access

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

Colin Deschanvres, Jacques Reynes, Isabelle Lamaury, David Rey, Romain Palich, Firouzé Bani‐Sadr, Olivier Robineau, Claudine Duvivier, Laurent Hocqueloux, Lise Cuzin, Véronique Joly, François Raffi, André Cabie, Clotilde Allavena, the Dat’AIDS Study Group, C Chirouze, C. Drobacheff-Thiébaut, Adeline Foltzer, Kévin Bouiller, Laurence Mathieu, Quentin Lepiller, Fabienne Bozon, O Babre, A-S Brunel, Patrice Muret, É. Chevalier, Christine Jacomet, Henri Laurichesse, O. Lesens, M. Vidal, Natacha Mrozek, C. Auméran, Olivier Baud, V. Corbin, E Goncalvez, Audrey Mirand, Alain Brebion, Cécile Henquell, Isabelle Lamaury, Isabelle Fabre, Elodie Curlier, Rachida Ouissa, Cécile Herrmann‐Storck, B. Tressières, M. C. Receveur, F Boulard, Corinne Daniel, C Clavel, Pierre Marie Roger, Samuel Markowicz, N Chellum Rungen, Dominique Merrien, P Perré, Thomas Guimard, O Bollangier, Sophie Leautez, Marine Morrier, Laetitia Laine, Daniel Boucher, P Point, Laurent Cotte, Florence Ader, Agathe Becker, A. Boibieux, Corinne Brochier, Florence Brunel-Dalmas, Olivier Cannesson, Pierre Chiarello, Christian Chidiac, S Degroodt, Tristan Ferry, Matthieu Godinot, J. M. Livrozet, Djamila Makhloufi, Patrick Miailhes, Thomas Perpoint, Melissa Perry, Cécile Pouderoux, Stanzi M. le Roux, Claire Triffault-Fillit, Florent Valour, Caroline Charre, Vinca Icard, Jean Claude Tardy, Mary‐Anne Trabaud, Isabelle Ravaux, A. Ménard, A Y Belkhir, Philippe Colson, C Dhiver, A Madrid, M Martin-Degioanni, Line Meddeb, Malika Mokhtarı, Anne Motte, Adrien G. Raoux, Christelle Tomei, Hervé Tissot‐Dupont, Isabelle Poizot‐Martin, Sylvie Brégigeon, Olivia Zaegel‐Faucher, Veronique Obry‐Roguet, Hélène Laroche, M Orticoni, M J Soavi, Emmanuelle Ressiot, M J Ducassou, Isabelle Jaquet, S Galie, H Colson, A S Ritleng, Alena Ivanova, Caroline Debreux, Caroline Lions, T Rojas-Rojas, André Cabie, Sylvie Abel, J Bavay, Bastien Bigeard, Ornella Cabras, Lise Cuzin, R Dupin de Majoubert, Laurence Fagour, Karine Guitteaud, Athena Marquise, Fatiha Najioullah, S. Pierre-François, Jérémie Pasquier, Pierre-Yves Richard, Katherine De Rome, J M Turmel, Catherine Varache, Nadine Atoui, Marie Bistoquet, Éric Delaporte, Vincent Le Moing, Alain Makinson, N Meftah, Corinne Merle De Boever, Brigitte Montès, Ana Ferrer, Édouard Tuaillon, Jacques Reynes, Benjamin Lefèvre, Eliette Jeanmaire, Sandrine Hénard, Emilia Frentiu, Alexandre Charmillon, Antoine Legoff, Nadine Tissot, Marie André, L. Boyer, M P Bouillon, M Delestan, François Goehringer, S Bevilacqua, Christian Rabaud, T. May, François Raffi, Clotilde Allavena, Olivier Aubry, Éric Billaud, Charlotte Biron, B. Bonnet, Sabelline Bouchez, David Boutoille, Cécile Brunet-Cartier, Colin Deschanvres, Benjamin Jean Gaborit, Antoine Grégoire, Matthieu Grégoire, Olivier Grossi, Romain Guéry, Thomas Jovelin, Anne‐Marie Lefebvre, Paul Le Turnier, Raphael Lecomte, P Morineau, Véronique Reliquet, Solène Sécher, M Cavellec, E. Paredes, Alessandro Soria, Virginie Ferré, Elisabeth André‐Garnier, Audrey Rodallec, Pascal Pugliese, Sophie Breaud, Carole Ceppi, David Chirio, Éric Cua, P. Dellamonica, Élisa Demonchy, Anne De Monte, Jacques Durant, C Etienne, Stephen J. Ferrando, R. Garraffo, C Michelangeli, V. Mondain, A. Naqvi, Nazan Tuna Oran, Isabelle Perbost, M Carles, Christian Klotz, A Maka, Christian Pradier, B Prouvost-Keller, Karine Risso, V Rio, Eric S. Rosenthal, Isabelle Touitou, S Wehrlen-Pugliese, G Zouzou, Laurent Hocqueloux, Thiérry Prazuck, Camelia Gubavu, Aymeric Sève, Susanna Giachè, Vincent Rzepecki, Michael Colin, Cendrine Boulard, Gaëlle Thomas, Antoine Chéret, Cécile Goujard, Yann Quertainmont, Elina Teicher, Nathalie Lerolle, Stéphane Jauréguiberry, R Colarino, O Deradji, Antonio Arjona Castro, Aurélie Barrail‐Tran, Yazdan Yazdanpanah, Roland Landman, Véronique Joly, Joumana Ghosn, C. Rioux, Sylvie Lariven, Anais Gervais, F.-X. Lescure, Sophie Matheron, Françoise Louni, Zélie Julia, Sylvie Le Gac, Charlotte Charpentier, Diane Descamps, Gilles Peytavin, Claudine Duvivier, Claire Aguilar, Fanny Alby‐Laurent, Karima Amazzough, Ghania Benabdelmoumen, Philippe Bossi, G Cessot, Caroline M. Charlier, Paul‐Henri Consigny, Kaoutar Jidar, Emmanuel Lafont, Fanny Lanternier, J. Leporrier, Olivier Lortholary, C Louisin, J. Lourenco, Perrine Parize, B. Pilmis, C. Rouzaud, F. Touam, M.A. Valantin, Roland Tubiana, Rachid Agher, Sophie Seang, L Schneider, Romain Palich, Catherine Blanc, Christine Katlama, Firouzé Bani‐Sadr, J L Berger, Yohan N’Guyen, D Lambert, Isabelle Kmiec, Maxime Hentzien, A. Brunet, Juliette Romaru, Hans Marty, Véronique Brodard, Cédric Arvieux, Pierre Tattevin, Mathieu Revest, Faouzi Souala, Marion Baldeyrou, S. Patrat-Delon, J.-M. Chapplain, François Bénézit, Magali Dupont, Mélanie Poinot, Anne Manuela Maillard, Charlotte Pronier, Florian Lemaitre, Clément Morlat, M Poisson-Vannier, J P Sinteff, Amandine Gagneux‐Brunon, Élisabeth Botelho-Nevers, Anne Fresard, V Ronat, F. Lucht, D. Rey, Patricia A. Fischer, Maria Partisani, Geneviève Chêne, M. Priester, Céline Melounou, Claudine Bernard-Henry, E de Mautort, Samira Fafi‐Kremer, Pierre Delobel, M Álvarez, N Biezunski, Alexa Debard, Cyrille Delpierre, Géraldine Gaube, P Lansalot, L Lelièvre, Mekeme Yon Marcel, Guillaume Martin‐Blondel, M Piffaut, Lorena Porte T, Karine Sauné, Olivier Robineau, F. Ajana, Emmanuelle Aïssi, Isabelle Alcaraz, Enagnon Kazali Alidjinou, Veronique Baclet, Laurence Bocket, Anne Boucher, Marc Digumber, T. Huleux, B. Lafon-Desmurs, Agnès Meybeck, M Pradier, Macha Tétart, P. Thill, Nathalie B. Viget, Michel Valette

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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.

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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.

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Available 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.

Key concepts: Dolutegravir, Rilpivirine, Emtricitabine, Medicine, Regimen, Lamivudine, Virology, Internal medicine

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Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting — Research Paper | ScholarLens