Anne-Genevieve Marcelin1, Maxime Grude1, Charlotte Charpentier2, Pantxika Bellecave3, Laura Le Guen4, Coralie Pallier5, Stéphanie Raymond6, Audrey Mirand7, Laurence Bocket8, Djeneba Bocar Fofana9, Constance Delaugerre10, Thuy Nguyen1, Brigitte Montès11, Hélène Jeulin12, Thomas Mourez13, Samira Fafi-Kremer14, Corinne Amiel15, Catherine Roussel16, Julia Dina17, Mary-Anne Trabaud18, Hélène Le Guillou-Guillemette19, Sophie Vallet20, Anne Signori-Schmuck21, Anne Maillard22, Virginie Ferre23, Diane Descamps2, Vincent Calvez1, Philippe Flandre1. 1. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, France. 2. INSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France. 3. CHU de Bordeaux, Laboratoire de Virologie, Université Bordeaux, CNRS UMR 5234, Bordeaux, France. 4. CHU de Nantes, Laboratoire de Virologie, Nantes, France. 5. CHU Paul Brousse, Villejuif, France. 6. INSERM U1043 Toulouse, F-31300 France and Laboratoire de Virologie, CHU Toulouse Purpan, Toulouse, France. 7. CHU de Clermont-Ferrand, Clermont-Ferrand, France. 8. CHU de Lille, Lille, France. 9. Sorbonne Université, INSERM, Institut Pierre Louis, d'Epidémiologie et de Santé Publique (IPLESP), AP-HP, Hôpital Saint Antoine, Service de Virologie, Paris, France. 10. CHU Saint Louis, Paris, France. 11. CHU Saint-Eloi, Montpellier, France. 12. Laboratoire de Virologie, CHRU de Nancy Brabois, Vandoeuvre-lès-Nancy, France. 13. CHU de Rouen, Rouen, France. 14. CHU de Strasbourg, Strasbourg, France. 15. AP-HP, CHU Tenon, Paris, France. 16. CHU d'Amiens, Amiens, France. 17. CHU de Caen, Caen, France. 18. Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France. 19. Laboratoire de Virologie, CHU Angers, Angers, France. 20. CHRU La Cavale Blanche, Brest, France. 21. CHU Grenoble-Alpes, Grenoble, France. 22. CHU de Rennes, Rennes, France. 23. CHU Nantes, Laboratoire de Virologie, CIC INSERM 143, Nantes, France.
Abstract
OBJECTIVES: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice. METHODS: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated. RESULTS: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure. CONCLUSIONS: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
OBJECTIVES: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice. METHODS: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated. RESULTS: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure. CONCLUSIONS: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
Authors: Philip L Tzou; Soo-Yon Rhee; Diane Descamps; Dana S Clutter; Bradley Hare; Orna Mor; Maxime Grude; Neil Parkin; Michael R Jordan; Silvia Bertagnolio; Jonathan M Schapiro; P Richard Harrigan; Anna Maria Geretti; Anne-Geneviève Marcelin; Robert W Shafer Journal: J Antimicrob Chemother Date: 2020-01-01 Impact factor: 5.790