by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

February 15, 2022

Featured Literature:
Landman R, de Truchis P, Assoumou L, et. al. ANRS 170 QUATUOR study group.  A 4-days-on and 3-days-off maintenance treatment strategy for adults with HIV-1 (ANRS 170 QUATUOR): a randomised, open-label, multicentre, parallel, non-inferiority trial.  Lancet HIV.  2022 Feb; 9(2): e79-e90.  doi: 10.1016/S2352-3018(21)00300-3.  PMID: 35120640

This randomized, open-label, non-inferiority trial examined 48-week efficacy, safety, and participant experience after switching to a 4-days-on, 3-days-off treatment strategy compared to standard daily continuous treatment using commonly prescribed ART combinations (INSTI, NNRTI, and PI-based regimens which included a 2 NRTI backbone).  636 participants were followed from 2018-2020 at multiple French hospitals: they were mostly male (85%) and had received ART for a median 6+ years, with a median 5.8 years of viral suppression < 50 copies/mL.  At week 48, in the mITT population, 96% in the intermittent treatment group and 97% in the continuous treatment group maintained plasma VL < 50 copies/mL with no treatment strategy modification, demonstrating non-inferiority [with the predefined margin of -5%].  Of 10 participants who experienced virologic failure, 3/6 in the intermittent group and 1/4 in the continuous treatment group developed new drug resistance mutations.  Grade 3-4 adverse events were reported in 9% vs. 12% of the intermittent and continuous treatment groups, respectively.  Daily life satisfaction improved in 59% of participants in the intermittent group vs. 7% of the continuous treatment group.

Author’s Commentary:

Results of this trial suggest that a 4-days-on, 3-days-off maintenance approach using contemporary 3-drug combinations yields a high rate of continued virologic suppression at 48 weeks among PWH without known HIV drug resistance.  Acceptability of, and adherence to, the maintenance regimen was also high, with many participants expressing high satisfaction with this approach.  Investigators note that ART costs were 43% lower with this intermittent, short-cycle strategy compared to continuous daily treatment (this approach may also be less expensive than some currently used dual oral ARV regimens).  As we continue gaining experience with regimen switch/simplification strategies, novel approaches such as this one – which actually seems relatively feasible to implement across a wide spectrum of clinical practice settings, compared to newer strategies i.e. long-acting injectable therapy – should be further tested to confirm long-term efficacy, safety, and generalizability.  

The author has no conflicts of interest to disclose.

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