Slim Fourati1, Charlotte Charpentier2, Corinne Amiel3, Laurence Morand-Joubert4, Sandrine Reigadas5, Mary-Anne Trabaud6, Constance Delaugerre7, Florence Nicot8, Audrey Rodallec9, Anne Maillard10, Audrey Mirand11, Hélène Jeulin12, Brigitte Montès13, Francis Barin14, Dominique Bettinger15, Hélène Le Guillou-Guillemette16, Sophie Vallet17, Anne Signori-Schmuck18, Diane Descamps2, Vincent Calvez1, Philippe Flandre1, Anne-Genevieve Marcelin19. 1. AP-HP, Hôpital Pitié-Salpêtrière, INSERM-Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France. 2. INSERM, IAME, UMR 1137, F-75018 Paris, France Université de Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Hôpital Bichat, Laboratoire de Virologie, F-75018 Paris, France. 3. AP-HP, CHU Tenon, Paris, France. 4. AP-HP, CHU Saint Antoine, INSERM-Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France. 5. CHU de Bordeaux, Laboratoire de Virologie, Université de Bordeaux, CNRS UMR 5234, F-33076 Bordeaux, France. 6. Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France. 7. CHU Saint Louis, Paris, France. 8. CHU de Toulouse, Hôpital Purpan, Laboratoire de virologie, F-31300 Toulouse, France. 9. CHU Nantes, Nantes, France. 10. CHU de Rennes, Rennes, France. 11. CHU de Clermont-Ferrand, Clermont-Ferrand, France. 12. CHU de Nancy, Nancy, France. 13. CHU Saint-Eloi, Montpellier, France. 14. CHU Tours, Tours, France. 15. CHU Saint Jacques, Besançon, France. 16. CHU Angers, Angers, France. 17. CHRU La Cavale Blanche, Brest, France. 18. CHU Grenoble, Grenoble, France. 19. AP-HP, Hôpital Pitié-Salpêtrière, INSERM-Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France anne-genevieve.marcelin@psl.aphp.fr.
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.
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.
Authors: Emmanuel Ndashimye; Mariano Avino; Abayomi S Olabode; Art F Y Poon; Richard M Gibson; Yue Li; Adam Meadows; Christine Tan; Paul S Reyes; Cissy M Kityo; Fred Kyeyune; Immaculate Nankya; Miguel E Quiñones-Mateu; Eric J Arts Journal: J Antimicrob Chemother Date: 2020-12-01 Impact factor: 5.790
Authors: James M Mikula; Maura M Manion; Frank Maldarelli; Lucila M Suarez; Jaha F Norman-Wheeler; Alex G Ober; Robin L Dewar; Jeffrey B Kopp; H Clifford Lane; Alice K Pau Journal: Antivir Ther Date: 2016-03-08
Authors: Tomas Doyle; David T Dunn; Francesca Ceccherini-Silberstein; Carmen De Mendoza; Frederico Garcia; Erasmus Smit; Esther Fearnhill; Anne-Genevieve Marcelin; Javier Martinez-Picado; Rolf Kaiser; Anna Maria Geretti Journal: J Antimicrob Chemother Date: 2015-08-26 Impact factor: 5.790