Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
24 12 2021
24 12 2021
Historique:
received:
12
04
2021
accepted:
02
09
2021
pubmed:
16
10
2021
medline:
4
3
2022
entrez:
15
10
2021
Statut:
ppublish
Résumé
Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Between 2014 and 2018, all HIV-1-infected adults included in the Dat'AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11-31) and 19 months (IQR = 11-31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28-6.93). No factor was associated with VF on dolutegravir/xTC. In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.
Sections du résumé
BACKGROUND
Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up.
OBJECTIVES
We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF.
METHODS
Between 2014 and 2018, all HIV-1-infected adults included in the Dat'AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF.
RESULTS
We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11-31) and 19 months (IQR = 11-31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28-6.93). No factor was associated with VF on dolutegravir/xTC.
CONCLUSIONS
In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.
Identifiants
pubmed: 34651192
pii: 6397219
doi: 10.1093/jac/dkab367
doi:
Substances chimiques
Anti-HIV Agents
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
Lamivudine
2T8Q726O95
dolutegravir
DKO1W9H7M1
Rilpivirine
FI96A8X663
Emtricitabine
G70B4ETF4S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
196-204Investigateurs
C Chirouze
(C)
C Drobacheff-Thiébaut
(C)
A Foltzer
(A)
K Bouiller
(K)
L Hustache-Mathieu
(L)
Q Lepiller
(Q)
F Bozon
(F)
O Babre
(O)
A S Brunel
(AS)
P Muret
(P)
E Chevalier
(E)
C Jacomet
(C)
H Laurichesse
(H)
O Lesens
(O)
M Vidal
(M)
N Mrozek
(N)
C Aumeran
(C)
O Baud
(O)
V Corbin
(V)
E Goncalvez
(E)
A Mirand
(A)
A Brebion
(A)
C Henquell
(C)
I Lamaury
(I)
I Fabre
(I)
E Curlier
(E)
R Ouissa
(R)
C Herrmann-Storck
(C)
B Tressieres
(B)
M C Receveur
(MC)
F Boulard
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C Daniel
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C Clavel
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P M Roger
(PM)
S Markowicz
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N Chellum Rungen
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D Merrien
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P Perré
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T Guimard
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O Bollangier
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S Leautez
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M Morrier
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L Laine
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D Boucher
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P Point
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L Cotte
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F Ader
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A Becker
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A Boibieux
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C Brochier
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F Brunel-Dalmas
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O Cannesson
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P Chiarello
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C Chidiac
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S Degroodt
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T Ferry
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M Godinot
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J M Livrozet
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D Makhloufi
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P Miailhes
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T Perpoint
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M Perry
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C Pouderoux
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C Triffault-Fillit
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F Valour
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J C Tardy
(JC)
M A Trabaud
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I Ravaux
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A Ménard
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A Y Belkhir
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P Colson
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C Dhiver
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A Madrid
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M Martin-Degioanni
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A Motte
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O Zaegel-Faucher
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M Orticoni
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M J Soavi
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E Ressiot
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M J Ducassou
(MJ)
I Jaquet
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S Galie
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H Colson
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A S Ritleng
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L Cuzin
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J M Turmel
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C Varache
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E Delaporte
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A Makinson
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C Merle de Boever
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B Montes
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A Montoya Ferrer
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E Tuaillon
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B J Gaborit
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A Grégoire
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O Grossi
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P Le Turnier
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P Morineau
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V Reliquet
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M Cavellec
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E Paredes
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A Soria
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V Ferré
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E André-Garnier
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A Rodallec
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J Durant
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A Naqvi
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I Perbost
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M Carles
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C Pradier
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A Brunet
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Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.