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Title
Dolutegravir monotherapy versus dolutegravir/abacavir/lamivudine for HIV-1-infected virologically suppressed patients: Results from the randomized non-inferiority MONCAY trial
Presenter
Laurent Hocqueloux
Authors
L. Hocqueloux1, C. Allavena2, T. Prazuck1, L. Bernard3, S. Sunder4, J.-L. Esnault5, D. Rey6, G. Le Moal7, M. Roncato-Saberan8, M. André9, E. Billaud2, V. Avettand-Fènoël10, A. Valéry11, F. Raffi2, J.-J. Parienti12, MONCAY Study Group
Institutions
1CHR d'Orléans - La Source, Infectious and Tropical Diseases, Orléans, France, 2CHU de Nantes, Infectious Diseases, Nantes, France, 3CHU de Tours, Infectious Diseases, Tours, France, 4CHG, Infectious Diseases, Niort, France, 5CHD, Infectious Diseases, La Roche sur Yon, France, 6CHU de Strasbourg, Infectious Diseases, Strasbourg, France, 7CHU de Poitiers, Infectious Diseases, Poitiers, France, 8CHG, Infectious Diseases, La Rochelle, France, 9CHU de Nancy, Infectious Diseases, Nancy, France, 10CHU Necker - Enfants Malades, APHP, Virology, Paris, France, 11CHR d'Orléans - La Source, Biostatistics, Orléans, France, 12CHU de Caen, Clinical Research and Biostatistics, Caen, France

Background: We investigated whether dolutegravir alone was able to maintain virological suppression in HIV-1-infected patients on a successful dolutegravir-based standardized triple-therapy.
Methods: MONCAY was a 48-week multicentric, randomized, open-label, 12% non-inferiority margin study. Inclusion criteria were: age ≥18 years, CD4 nadir >100/µl, no previous AIDS event, plasma HIV-RNA (pVL) < 50 copies/ml for ≥12 months, stable regimen with once daily dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and no failure or resistance to any integrase inhibitor (INI). Patients were 1:1 randomized to continue DTG/ABC/3TC or to simplify to DTG monotherapy. The primary endpoint was the proportion of patients with pVL < 50 copies/ml at week (W) 24 in intention-to-treat (ITT), missing or switch equals failure (M=F); modified ITT (mITT) excluding patients who had non-inclusion criteria; Per-protocol (PP) excluding from mITT patients with major protocol deviation. Virologic failure (VF) was defined as two consecutive pVL >50 copies/ml within 2 weeks apart.
Results: Seventy-eight patients were assigned to DTG and 80 to continue DTG/ABC/3TC. Of these 158 patients, 3 had non-inclusion criteria and 6 had major protocol deviation in the DTG arm; 2 had non-inclusion criteria and 1 had major protocol deviation in the DTG/ABC/3TC arm. By W24, 2 patients in DTG group experienced VF (both at W24) without resistance to the INI class; 1 patient stopped DTG/ABC/3TC due to adverse event (at W4). In ITT (n=158), the success rate was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm; difference 3.9%, 95%CI: -5.0 to 10.8. This figure was 1.4%; 95%CI: -4.5 to 8.1 in mITT (n=153) and 1.6%; 95%CI: -4.5 to 8.8 in PP (n=146). During subsequent follow-up, 3 additional patients in the DTG arm experienced VF (2 at W36 and 1 at W48) with emerging resistance mutations to INI in 2 cases, whereas none occurred in the DTG/ABC/3TC group (difference 6.5%, 95%CI: -1.8 to 15.6). The DSMB recommended to re-intensify the DTG arm with standardized triple-therapy.
Conclusions: Although non-inferior to DTG/ABC/3TC at W24, DTG monotherapy was not a valid option to maintain virological suppression overtime in HIV-1-infected patients on a successful DTG/ABC/3TC triple-therapy and favoured emergence of INI resistance.