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

• Published in: British journal of clinical pharmacology Vol. 87; no. 4; pp. 1930 - 1939
• Main Authors: Abe, Emuri, Assoumou, Lambert, Truchis, Pierre, Amat, Karine, Gibowski, Séverine, Gras, Guillaume, Bellet, Jonathan, Saillard, Juliette, Katlama, Christine, Costagliola, Dominique, Girard, Pierre‐Marie, Landman, Roland, Alvarez, Jean‐Claude
• Format: Journal Article
• Language: English
• Published: England Wiley 01.04.2021
• Subjects: antiretroviral plasma concentration; dose reduction; HIV infection; Life Sciences; short‐cycle therapy; therapeutic drug monitoring; dose reduction; short-cycle therapy; antiretroviral plasma concentration; HIV infection; therapeutic drug monitoring
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.14586

Introduction Few data are available on plasma concentrations of antiretroviral therapy (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 two nucleoside analogues and a third agent belonging to a 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% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF). Results A total of 866 samples was analysed. 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 for 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. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable. Conclusion Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.