Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)

INTRODUCTION Few data are available on plasma concentrations of ARV during intermittent treatment. OBJECTIVE to compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment. METHODS During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by 2 nucleosides analogs and a third agent belonging to boosted protease-inhibitor (PI, Darunavir-DRV, Atazanavir-ATV, Lopinavir-LPV) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, Efavirenz-EFV, Etravirine-ETR, Rilpivirine-RPV) conducted in 100 patients (96% of success), we determined plasma concentrations of ARV. Blood samples were collected for analysis at W0 (7/7 strategy at inclusion), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF). RESULTS A total of 866 samples were analyzed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (-30 ng/mL at 4/7, P=0.003). Significant lower plasma concentrations were observed on OFF vs ON except for ETR (n=5, p=0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100%, and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6%, and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. On OFF period, 85.8% of PIs concentrations were under the limit of quantification, while 98.0% of NNRTIs concentrations were quantifiable. CONCLUSION Despite low/undetectable PI/NNRTI plasma concentrations on OFF period, patients maintained undetectable viral load. Mechanistic explanation should be investigated.