Background: Intermittent treatment could improve the convenience, tolerability and cost of ART. We have previously shown a 96% success rate of a maintenance 4 days a week (4/7 days) antiretroviral strategy in the ANRS 162 4D pilot study. The current study was designed to demonstrate the non-inferiority of this strategy versus 7/7 days in patients with controlled viral load (VL) under triple therapy with either PI, NNRTI, or InSTI based regimen.
Methods: We conducted an open-label, randomised, multicentric, non-inferiority phase III trial evaluating efficacy and safety of a maintenance 4-days a week therapy (4/7 days) versus current triple ART regimen (CAR). Adults with plasma VL< 50 copies/mL for >12 months and no resistance mutations to CAR were randomly assigned (1:1) with stratification by third-agent class. The primary endpoint was the Kaplan-Meier estimated proportion of participants with treatment success (VL< 50 copies/mL and no treatment strategy modification) at week 48 among those starting the study strategy. We calculated the Cochran-Mantel-Haenszel treatment difference adjusted for the stratification factor, with a 5% non-inferiority margin. ClinicalTrials.gov: NCT03256422.
Results: Participants were screened from Sep 7, 2017, to Jan 22, 2018. Among 647 randomised participants, 636 were included in the modified intent-to-treat analysis (318 in each arm). At entry, median age was 49 years (IQR 41-55), 85% were male, with VL< 50 copies/ml for 5.8 (3.3-9.6) years, median CD4 689 (533-884) cells/mL; NRTI: 56.3% TDF/FTC, 16.3% TAF/FTC, 27.4% ABC/3TC; 3rd agent: 6% PI, 46% NNRTI, 48% InSTI. At week 48 (last patient visit was April 4, 2019), the treatment success rate was 95.6% in the 4/7 days arm vs 97.2% with CAR (adjusted difference of -1.6%, 95% CI -4.5% to 1.3%), demonstrating the non-inferiority. Six (1.9%) and 4 (1.3%) participants experienced virological failure with selection of resistance mutations in 3 and 1, respectively. No difference in adverse events was observed between the two arms. A moderate improvement of eGFR was observed in the 4/7 days arm, +5.5[-1.2-+13.6] ml/min vs +1.3[-6.1-+7.5] ml/min in CAR, P< 0.001.
Conclusions: The ANRS 170 QUATUOR randomised trial demonstrates the non-inferiority of a 4/7 days maintenance strategy vs a 7/7 days regimen.