Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial). Issue 4 (5th November 2020)

• Record Type: Journal Article
• Authors: Abe, Emuri; Assoumou, Lambert; de Truchis, Pierre; Amat, Karine; Gibowski, Séverine; Gras, Guillaume; Bellet, Jonathan; Saillard, Juliette; Katlama, Christine; Costagliola, Dominique; Girard, Pierre‐Marie; Landman, Roland; Alvarez, Jean‐Claude
• Is Part Of: British journal of clinical pharmacology. Volume 87:Issue 4(2021)
• Page Start: 1930
• Page End: 1939
• Publication Date: 2020-11-05
• Subjects: antiretroviral plasma concentration -- dose reduction -- HIV infection -- short‐cycle therapy -- therapeutic drug monitoring; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.14586
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : 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.