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

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

doi:10.1093/jac/dkab367

Abstract

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. 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. 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. 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. 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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