Anne-Genevieve Marcelin1, Charlotte Charpentier2, Pantxika Bellecave3, Basma Abdi1, Marie-Laure Chaix4, Virginie Ferre5, Stephanie Raymond6, Djeneba Fofana7, Laurence Bocket8, Audrey Mirand9, Helene Le Guillou-Guillemette10, Brigitte Montes11, Corinne Amiel12, Coralie Pallier13, Samira Fafi-Kremer14, Anne De Monte15, Elodie Alessandri-Gradt16, Caroline Scholtes17, Anne Maillard18, Helene Jeulin19, Magali Bouvier-Alias20, Catherine Roussel21, Georges Dos Santos22, Anne Signori-Schmuck23, Julia Dina24, Sophie Vallet25, Karl Stefic26, Cathia Soulié1, Vincent Calvez1, Diane Descamps3, Philippe Flandre27. 1. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, laboratoire de virologie, F-75013 Paris, France. 2. Service de Virologie, Université de Paris INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude-Bernard, F-75018 Paris, France. 3. CHU de Bordeaux, Laboratoire de Virologie, Univ. Bordeaux, CNRS UMR 5234, F-33076 Bordeaux, France. 4. INSERM U941, Université de Paris, Laboratoire de Virologie, AP-HP, Hôpital Saint-Louis, Paris, France. 5. CHU Nantes, Laboratoire de Virologie, CIC INSERM 143, F-44093 Nantes, France. 6. INSERM UMR 1291 Toulouse, F-31300 France and Laboratoire de Virologie, CHU Toulouse Purpan, F-31300 Toulouse, France. 7. AP-HP, CHU Saint Antoine, INSERM-Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75012 Paris, France. 8. Univ. Lille, CHU Lille, Laboratoire de Virologie, Lille, France. 9. CHU de Clermont-Ferrand, France. 10. Laboratoire de Virologie, CHU Angers and HIFIH Laboratory EA 3859, LUNAM, Angers, France. 11. Laboratoire de Virologie, CHU Montpellier, Univ Montpellier, France. 12. AP-HP, CHU Tenon, Paris, France. 13. CHU Paul Brousse, Villejuif, France. 14. CHU de Strasbourg, Strasbourg, France. 15. CHU de Nice, Nice, France. 16. CHU de Rouen, Université de Rouen Normandie, Rouen, France. 17. INSERM U1052, CRCL, Université de Lyon, Laboratoire de Virologie, Lyon, France. 18. Laboratoire de Virologie, CHU de Rennes, Rennes, France. 19. Laboratoire de Virologie, CHRU de Nancy Brabois, Vandoeuvre-lès-Nancy, France. 20. CHU Henri Mondor, Laboratoire de Virologie, Créteil, France. 21. CHU d'Amiens, Amiens, France. 22. Service de virologie, CHU de Martinique, Fort de France, Martinique. 23. CHU Grenoble-Alpes, Grenoble, France. 24. Normandie Univ, UNICAEN, UNIROUEN, GRAM 2.0, Caen University Hospital Department of Virology, F-14000, Caen, France. 25. Laboratoire de Virologie, CHRU de Brest, Brest, France. 26. INSERM U1259, Université de Tours et Laboratoire de Virologie, CHRU de Tours, Tours, France. 27. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Abstract
BACKGROUND: Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. MATERIALS AND METHODS: A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. RESULTS: Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0-0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. CONCLUSIONS: This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.
BACKGROUND: Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. MATERIALS AND METHODS: A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. RESULTS: Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0-0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. CONCLUSIONS: This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.