Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients
Authors: Fourati Slim , Charpentier Charlotte , Amiel Corinne , Morand-Joubert Laurence , Reigadas Sandrine , Trabaud Mary-Anne , Delaugerre Constance , Nicot Florence , Rodallec Audrey , Maillard Anne , Mirand Audrey , Jeulin Hélène , Montès Brigitte , Barin Francis , Bettinger Dominique , Le Guillou-Guillemette Hélène , Vallet Sophie , Signori-Schmuck Anne , Descamps Diane , Calvez Vincent , Flandre Philippe , Marcelin Anne-Genevieve ,   on behalf of the ANRS AC11 Resistance Study Group, 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. 
Published: January 2015

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 &lt; 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P &lt; 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.