Dolutegravir Monotherapy Versus Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed People Living With Chronic Human Immunodeficiency Virus Infection: The Randomized Noninferiority MONotherapy of TiviCAY Trial
Authors: Hocqueloux Laurent , Raffi François , Prazuck Thierry , Bernard Louis , Sunder Simon , Esnault Jean-Luc , Rey David , Le Moal Gwenaël , Roncato-Saberan Mariam , André Marie , Billaud Eric , Valéry Antoine , Avettand-Fènoël Véronique , Parienti Jean-Jacques , Allavena Clotilde ,   MONCAY study group, Bollengier-Stragier Olivier , Esnault Jean-Luc , Guimard Thomas , Leautez Sophie , Perré Philippe , Lemarie Romain , Pouget-Abadie Xavier , Roncato-Saberan Mariam , André Marie , May Thierry , Schvoerer Evelyne , Allavena Clotilde , Andre-Garnier Elisabeth , Bernaud Camille , Billaud Eric , Bouchez Sabelline , Hall Nolwenn , Raffi François , Reliquet Véronique , Vivrel Florian , Deleplanque Pascale , Dos-Santos Anabele , Sunder Simon , Boulard Cendrine , Despujols Aurélie , Guinard Jérôme , Hocqueloux Laurent , Lefeuvre Sandrine , Mille Catherine , Niang Mohamadou , Ouezzani Montasser , Prazuck Thierry , Thomas Gaëlle , Valéry Antoine , Avettand-Fènoël Véronique , Giraudeau Geneviève , Le Moal Gwenaël , Batard Marie-Laure , Fafi-Kremer Samira , Rey David , Barin Francis , Bastides Frédéric , Bernard Louis , Gras Guillaume , Hallouin-Bernard Marie Charlotte , Lemaignen Adrien , Le Bret Pascal , Stefic Karl 
Published: December 2018

Abstract

Background
We investigated whether dolutegravir (DTG) monotherapy could be used to maintain virological suppression in people living with human immunodeficiency virus (HIV) on a successful dolutegravir-based triple therapy.

Methods
MONCAY (MONotherapy of TiviCAY) was a 48-week, multicentric, randomized, open-label, 12% noninferiority margin trial. Patients with CD4 nadir >100/μL, plasma HIV-1 RNA <50 copies/mL for ≥12 months, and stable regimen with DTG/abacavir (ABC)/lamivudine (3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 24 in intention-to-treat snapshot analysis. Virologic failure (VF) was defined as 2 consecutive HIV RNA >50 copies/mL within 2 weeks apart.

Results
Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By week 24, 2 patients in the DTG group experienced VF without resistance to the integrase strand transfer inhibitor (INSTI) class; 1 patient discontinued DTG/ABC/3TC due to an adverse event. The success rate at week 24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm (difference, 2.7%; 95% confidence interval [CI], –5.0 to 10.8). During subsequent follow-up, 5 additional VFs occurred in the DTG arm (2 of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at week 48 was 9.7% (95% CI, 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (P = .005 by the log-rank test). The Data Safety Monitoring Board recommended to reintensify the DTG arm with standardized triple therapy.

Conclusions
Because the risk of VF with resistance increases over time, we recommend avoiding DTG monotherapy as a maintenance strategy among people living with chronic HIV infection.

Clinical Trials Registration
NCT02596334 and EudraCT 2015-002853-36.