Plasma concentrations of antiretroviral drugs in a successful 4-days-a-week maintenance treatment strategy in HIV-1 patients (ANRS 170-Quatuor trial)

Abstract

Abstract Objectives Charaterization of the plasma concentrations of antiretrovirals in a 4-days-a-week maintenance treatment strategy in the ANRS-170-QUATUOR study. Methods Patients were randomized in two groups receiving triple therapy taken 4-days-ON and 3-days-OFF (4/7) or continuous therapy (7/7). Plasma antiretroviral concentrations were monitored during the ‘ON-treatment period’ (Day 3 or 4 of the 4-day treatment block) and the ‘OFF-treatment period’ (Day 3 of the 3-day drug cessation) for the 4/7 group, or before the daily drug intake for the 7/7 group, until week-48 (W48). After W48, all patients switched to the 4/7 strategy and were followed until W96. Results W0 measured concentrations were comparable in both groups, except for raltegravir, concentrations of which were higher in the 4/7 group, and were all above the values usually recommended to be effective in therapeutic drug monitoring. Comparison of ON-period median concentrations between the two groups showed a statistical difference for rilpivirine [88 ng/mL (interquartile range (IQR) = 64–112) for 4/7 arm versus 130 ng/mL (82–160) for 7/7 arm, P < 0.001] and tenofovir [tenofovir disoproxil fumarate: 93 ng/mL (73–135) for 4/7 arm versus 117 ng/mL (83–160) for 7/7 arm, P < 0.001; tenofovir alafenamide: 11 ng/mL (7–15) for 4/7 arm versus 14 ng/mL (11–18) for 7/7 arm, P = 0.001]. Median OFF concentrations were significantly lower (P < 0.001) at the 48 week analysis for all medications except for raltegravir (P = 0.493) and atazanavir (P = 0.105), for which the numbers of patients were very small. Conclusions The 4/7-day treatment option led to antiretroviral blood levels close to continuous treatment after the four consecutive days of medication, and to low levels at the end of the non-treatment period.