Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting
Authors: Deschanvres Colin , Reynes Jacques , Lamaury Isabelle , Rey David , Palich Romain , Bani-Sadr Firouzé , Robineau Olivier , Duvivier Claudine , Hocqueloux Laurent , Cuzin Lise , Joly Veronique , Raffi Francois , Cabie André , Allavena Clotilde ,   the Dat’AIDS Study Group, Chirouze C , Drobacheff-Thiébaut C , Foltzer A , Bouiller K , Hustache- Mathieu L , Lepiller Q , Bozon F , Babre O , Brunel A S , Muret P , Chevalier E , Jacomet C , Laurichesse H , Lesens O , Vidal M , Mrozek N , Aumeran C , Baud O , Corbin V , Goncalvez E , Mirand A , Brebion A , Henquell C , Lamaury I , Fabre I , Curlier E , Ouissa R , Herrmann-Storck C , Tressieres B , Receveur M C , Boulard F , Daniel C , Clavel C , Roger P M , Markowicz S , Chellum Rungen N , Merrien D , Perré P , Guimard T , Bollangier O , Leautez S , Morrier M , Laine L , Boucher D , Point P , Cotte L , Ader F , Becker A , Boibieux A , Brochier C , Brunel-Dalmas F , Cannesson O , Chiarello P , Chidiac C , Degroodt S , Ferry T , Godinot M , Livrozet J M , Makhloufi D , Miailhes P , Perpoint T , Perry M , Pouderoux C , Roux S , Triffault-Fillit C , Valour F , Charre C , Icard V , Tardy J C , Trabaud M A , Ravaux I , Ménard A , Belkhir A Y , Colson P , Dhiver C , Madrid A , Martin-Degioanni M , Meddeb L , Mokhtari M , Motte A , Raoux A , Toméi C , Tissot-Dupont H , Poizot-Martin I , Brégigeon S , Zaegel-Faucher O , Obry-Roguet V , Laroche H , Orticoni M , Soavi M J , Ressiot E , Ducassou M J , Jaquet I , Galie S , Colson H , Ritleng A S , Ivanova A , Debreux C , Lions C , Rojas-Rojas T , Cabié A , Abel S , Bavay J , Bigeard B , Cabras O , Cuzin L , Dupin de Majoubert R , Fagour L , Guitteaud K , Marquise A , Najioullah F , Pierre-François S , Pasquier J , Richard P , Rome K , Turmel J M , Varache C , Atoui N , Bistoquet M , Delaporte E , Le Moing V , Makinson A , Meftah N , Merle de Boever C , Montes B , Montoya Ferrer A , Tuaillon E , Reynes J , Lefèvre B , Jeanmaire E , Hénard S , Frentiu E , Charmillon A , Legoff A , Tissot N , André M , Boyer L , Bouillon M P , Delestan M , Goehringer F , Bevilacqua S , Rabaud C , May T , Raffi F , Allavena C , Aubry O , Billaud E , Biron C , Bonnet B , Bouchez S , Boutoille D , Brunet-Cartier C , Deschanvres C , Gaborit B J , Grégoire A , Grégoire M , Grossi O , Guéry R , Jovelin T , Lefebvre M , Le Turnier P , Lecomte R , Morineau P , Reliquet V , Sécher S , Cavellec M , Paredes E , Soria A , Ferré V , André-Garnier E , Rodallec A , Pugliese P , Breaud S , Ceppi C , Chirio D , Cua E , Dellamonica P , Demonchy E , De Monte A , Durant J , Etienne C , Ferrando S , Garraffo R , Michelangeli C , Mondain V , Naqvi A , Oran N , Perbost I , Carles M , Klotz C , Maka A , Pradier C , Prouvost-Keller B , Risso K , Rio V , Rosenthal E , Touitou I , Wehrlen-Pugliese S , Zouzou G , Hocqueloux L , Prazuck T , Gubavu C , Sève A , Giaché S , Rzepecki V , Colin M , Boulard C , Thomas G , Cheret A , Goujard C , Quertainmont Y , Teicher E , Lerolle N , Jaureguiberry S , Colarino R , Deradji O , Castro A , Barrail-Tran A , Yazdanpanah Y , Landman R , Joly V , Ghosn J , Rioux C , Lariven S , Gervais A , Lescure F X , Matheron S , Louni F , Julia Z , Le Gac S , Charpentier C , Descamps D , Peytavin G , Duvivier C , Aguilar C , Alby-Laurent F , Amazzough K , Benabdelmoumen G , Bossi P , Cessot G , Charlier C , Consigny P H , Jidar K , Lafont E , Lanternier F , Leporrier J , Lortholary O , Louisin C , Lourenco J , Parize P , Pilmis B , Rouzaud C , Touam F , Valantin M A , Tubiana R , Agher R , Seang S , Schneider L , Palich R , Blanc C , Katlama C , Bani-Sadr F , Berger J L , N’Guyen Y , Lambert D , Kmiec I , Hentzien M , Brunet A , Romaru J , Marty H , Brodard V , Arvieux C , Tattevin P , Revest M , Souala F , Baldeyrou M , Patrat-Delon S , Chapplain J M , Benezit F , Dupont M , Poinot M , Maillard A , Pronier C , Lemaitre F , Morlat C , Poisson-Vannier M , Sinteff J P , Gagneux-Brunon A , Botelho-Nevers E , Frésard A , Ronat V , Lucht F , Rey D , Fischer P , Partisani M , Cheneau C , Priester M , Mélounou C , Bernard-Henry C , de Mautort E , Fafi-Kremer S , Delobel P , Alvarez M , Biezunski N , Debard A , Delpierre C , Gaube G , Lansalot P , Lelièvre L , Marcel M , Martin-Blondel G , Piffaut M , Porte L , Saune K , Robineau O , Ajana F , Aïssi E , Alcaraz I , Alidjinou E , Baclet V , Bocket L , Boucher A , Digumber M , Huleux T , Lafon-Desmurs B , Meybeck A , Pradier M , Tetart M , Thill P , Viget N , Valette M 
Published: September 2021

Abstract

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 &gt;50 copies/mL or a single value &gt;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.