Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting
Colin Deschanvres
(1, 2)
,
Jacques Reynes
(3, 4, 2)
,
Isabelle Lamaury
(5, 2)
,
David Rey
(6, 2)
,
Romain Palich
(7, 2)
,
Firouzé Bani-Sadr
(8, 2)
,
Olivier Robineau
(9, 2, 10)
,
Claudine Duvivier
(11, 2)
,
Laurent Hocqueloux
(12, 2)
,
Lise Cuzin
(13, 14, 2)
,
Veronique Joly
(15, 2)
,
Francois Raffi
(1, 2)
,
André Cabie
(14, 2)
,
Clotilde Allavena
(1, 2)
,
C Chirouze
(2)
,
C Drobacheff-Thiébaut
(2)
,
A Foltzer
(2)
,
K Bouiller
(2)
,
L Hustache- Mathieu
(2)
,
Q Lepiller
(2)
,
F Bozon
(2)
,
O Babre
(2)
,
A Brunel
(2)
,
P Muret
(2)
,
E Chevalier
(2)
,
C Jacomet
(2)
,
H Laurichesse
(2)
,
O Lesens
(2)
,
M Vidal
(2)
,
N Mrozek
(2)
,
C Aumeran
(2)
,
O Baud
(2)
,
V Corbin
(2)
,
E Goncalvez
(2)
,
A Mirand
(2, 16, 17)
,
A Brebion
(2)
,
C Henquell
(2)
,
I Fabre
(2)
,
E Curlier
(2)
,
R Ouissa
(2)
,
C Herrmann-Storck
(2)
,
B Tressieres
(2)
,
M Receveur
(2)
,
F Boulard
(2)
,
C Daniel
(2)
,
C Clavel
(2)
,
P Roger
(2)
,
S Markowicz
(2)
,
N Chellum Rungen
(2)
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D Merrien
(2)
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P Perré
(2)
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T Guimard
(2)
,
O Bollangier
(2)
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S Leautez
(2)
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M Morrier
(2)
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L Laine
(2)
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D Boucher
(2)
,
P Point
(2)
,
L Cotte
(2)
,
F Ader
(2)
,
A Becker
(2)
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(2)
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C Brochier
(2)
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F Brunel-Dalmas
(2)
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O Cannesson
(2)
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J Tardy
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A Ménard
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A 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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L Meddeb
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1
Service des maladies infectieuses et tropicales [CHU Nantes]
2 Dat’AIDS Study Group
3 Département Maladies Infectieuses et Tropicales [CHRU Montpellier]
4 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
5 CHU Pointe-à-Pitre / Abymes [Guadeloupe]
6 HUS - Les Hôpitaux Universitaires de Strasbourg
7 CHU Pitié-Salpêtrière [AP-HP]
8 CHU Reims - Hôpital universitaire Robert Debré [Reims]
9 Centre Hospitalier Gustave Dron [Tourcoing]
10 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694
11 IP - Institut Pasteur [Paris]
12 CHRO - Centre Hospitalier Régional d'Orléans
13 Equipe EQUITY (CERPOP)
14 CHU de Martinique - Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
15 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
16 CHU Clermont-Ferrand
17 UCA - Université Clermont Auvergne
2 Dat’AIDS Study Group
3 Département Maladies Infectieuses et Tropicales [CHRU Montpellier]
4 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
5 CHU Pointe-à-Pitre / Abymes [Guadeloupe]
6 HUS - Les Hôpitaux Universitaires de Strasbourg
7 CHU Pitié-Salpêtrière [AP-HP]
8 CHU Reims - Hôpital universitaire Robert Debré [Reims]
9 Centre Hospitalier Gustave Dron [Tourcoing]
10 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694
11 IP - Institut Pasteur [Paris]
12 CHRO - Centre Hospitalier Régional d'Orléans
13 Equipe EQUITY (CERPOP)
14 CHU de Martinique - Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
15 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
16 CHU Clermont-Ferrand
17 UCA - Université Clermont Auvergne
Colin Deschanvres
- Fonction : Auteur
- PersonId : 799508
- ORCID : 0000-0002-1133-5207
Romain Palich
- Fonction : Auteur
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- IdHAL : romain-palich
- ORCID : 0000-0003-0047-0101
Firouzé Bani-Sadr
- Fonction : Auteur
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- IdRef : 120562642
Laurent Hocqueloux
- Fonction : Auteur
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- ORCID : 0000-0002-2264-4822
Lise Cuzin
- Fonction : Auteur
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- IdRef : 058114661
Clotilde Allavena
- Fonction : Auteur
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- ORCID : 0000-0003-1010-1270
C Chirouze
- Fonction : Auteur
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K Bouiller
- Fonction : Auteur
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- IdHAL : kevin-bouiller
- ORCID : 0000-0002-2177-4318
S Seang
- Fonction : Auteur
- PersonId : 1213628
- IdHAL : sophie-seang
- ORCID : 0000-0001-7724-9312
E Botelho-Nevers
- Fonction : Auteur
- PersonId : 1452409
- IdHAL : ebotelhonevers
- ORCID : 0000-0003-2773-7750
- IdRef : 128018674
S Fafi-Kremer
- Fonction : Auteur
- PersonId : 1062952
- ORCID : 0000-0003-3886-7833
- IdRef : 094693501
C Delpierre
- Fonction : Auteur
- PersonId : 943421
- IdHAL : cyrille-delpierre
- ORCID : 0000-0002-0831-080X
- IdRef : 11104491X
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.