Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients
Author:
Fourati Slim1, Charpentier Charlotte234, Amiel Corinne5, Morand-Joubert Laurence6, Reigadas Sandrine7, Trabaud Mary-Anne8, Delaugerre Constance9, Nicot Florence10, Rodallec Audrey11, Maillard Anne12, Mirand Audrey13, Jeulin Hélène14, Montès Brigitte15, Barin Francis16, Bettinger Dominique17, Le Guillou-Guillemette Hélène18, Vallet Sophie19, Signori-Schmuck Anne20, Descamps Diane234, Calvez Vincent1, Flandre Philippe1, Marcelin Anne-Genevieve1, Lagier E., Roussel C., Le Guillou H., Alloui C., Bettinger D., Pallier C., Fleury H., Reigadas S., Bellecave P., Recordon-Pinson P., Payan C., Vallet S., Vabret A., Henquell C., Mirand A., Bouvier-Alias M., de Rougemont A., Dos Santos G., Morand P., Signori-Schmuck A., Bocket L., Rogez S., Andre P., Tardy J. C., Trabaud M. A., Tamalet C., Delamare C., Montes B., Schvoerer E., Ferre V., André-Garnier E., Cottalorda J., Guinard J., Guiguon A., Descamps D., Brun-Vézinet F., Charpentier C., Visseaux B., Peytavin G., Krivine A., Si-Mohamed A., Avettand-Fenoel V., Marcelin A. G., Calvez V., Lambert-Niclot S., Soulié C., Wirden M., Morand-Joubert L., Delaugerre C., Chaix M. L., Amiel C., Schneider V., Giraudeau G., Brodard V., Maillard A., Plantier J. C., Chaplain C., Bourlet T., Fafi-Kremer S., Stoll-Keller F., Schmitt M. P., Barth H., Yerly S., Poggi C., Izopet J., Raymond S., Barin F., Chaillon A., Marque-Juillet S., Roque-Afonso A. M., Haïm-Boukobza S., Flandre P., Grudé M., Assoumou L., Costagliola D., Allegre T., Schmit J. L., Chennebault J. M., Bouchaud O., Magy-Bertrand N., Delfraissy J. F., Dupon M., Morlat P., Neau D., Ansart S., Jaffuel S., Verdon R., Jacomet C., Lévy Y., Dominguez S., Chavanet P., Piroth L., Cabié A., Leclercq P., Ajana F., Cheret A., Weinbreck P., Cotte L., Poizot-Martin I., Ravaud I., Christian B., Truchetet F., Grandidier M., Reynes J., May T., Goehringer F., Raffi F., Dellamonica P., Prazuck T., Hocqueloux L., Yéni P., Landman R., Launay O., Weiss L., Viard J. P., Katlama C., Simon A., Girard P.M., Meynard J. L., Molina J. M., Pialoux G., Hoen B., Goeger-Sow M. T., Lamaury I., Beaucaire G., Jaussaud R., Rouger C., Michelet C., Borsa-Lebas F., Caron F., Khuong M. A., Lucht F., Rey D., Calmy A., Marchou B., Gras G., Greder-Belan A., Vittecoq D., Teicher E.,
Affiliation:
1. 1 AP-HP, Hôpital Pitié-Salpêtrière, INSERM-Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France 2. 2 INSERM, IAME, UMR 1137, F-75018 Paris, France 3. 3 Université de Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France 4. 4 AP-HP, Hôpital Bichat, Laboratoire de Virologie, F-75018 Paris, France 5. 5 AP-HP, CHU Tenon, Paris, France 6. 6 AP-HP, CHU Saint Antoine, INSERM-Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France 7. 7 CHU de Bordeaux, Laboratoire de Virologie, Université de Bordeaux, CNRS UMR 5234, F-33076 Bordeaux, France 8. 8 Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France 9. 9 CHU Saint Louis, Paris, France 10. 10 CHU de Toulouse, Hôpital Purpan, Laboratoire de virologie, F-31300 Toulouse, France 11. 11 CHU Nantes, Nantes, France 12. 12 CHU de Rennes, Rennes, France 13. 13 CHU de Clermont-Ferrand, Clermont-Ferrand, France 14. 14 CHU de Nancy, Nancy, France 15. 15 CHU Saint-Eloi, Montpellier, France 16. 16 CHU Tours, Tours, France 17. 17 CHU Saint Jacques, Besançon, France 18. 18 CHU Angers, Angers, France 19. 19 CHRU La Cavale Blanche, Brest, France 20. 20 CHU Grenoble, Grenoble, France
Abstract
Abstract
Objectives
The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).
Patients and methods
Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).
Results
Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004).
Conclusions
This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)
Cited by
51 articles.
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