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.