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J Antimicrob Chemother. 2015 May;70(5):1507-12. doi: 10.1093/jac/dku535. Epub 2015 Jan 3.

Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients.

Collaborators (139)

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 JC, Trabaud MA, 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 AG, Calvez V, Lambert-Niclot S, Soulié C, Wirden M, Morand-Joubert L, Delaugerre C, Chaix ML, Amiel C, Schneider V, Giraudeau G, Brodard V, Maillard A, Plantier JC, Chaplain C, Bourlet T, Fafi-Kremer S, Stoll-Keller F, Schmitt MP, Barth H, Yerly S, Poggi C, Izopet J, Raymond S, Barin F, Chaillon A, Marque-Juillet S, Roque-Afonso AM, Haïm-Boukobza S, Flandre P, Grudé M, Assoumou L, Costagliola D, Allegre T, Schmit JL, Chennebault JM, Bouchaud O, Magy-Bertrand N, Delfraissy JF, 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 JP, Katlama C, Simon A, Girard PM, Meynard JL, Molina JM, Pialoux G, Hoen B, Goeger-Sow MT, Lamaury I, Beaucaire G, Jaussaud R, Rouger C, Michelet C, Borsa-Lebas F, Caron F, Khuong MA, Lucht F, Rey D, Calmy A, Marchou B, Gras G, Greder-Belan A, Vittecoq D, Teicher E.

Author information

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.

KEYWORDS:

inhibitors; integrase; mutations; patterns

PMID:
25558077
DOI:
10.1093/jac/dku535
[Indexed for MEDLINE]

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