Pharmacological data of a successful 4-days-a-week regimen in HIV antiretroviral therapy (ANRS 162-4D trial).
HIV infection
antiretroviral plasma concentration
dose reduction
short-cycle therapy
therapeutic drug monitoring
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
16
09
2020
received:
06
07
2020
accepted:
21
09
2020
pubmed:
4
10
2020
medline:
27
7
2021
entrez:
3
10
2020
Statut:
ppublish
Résumé
Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment. To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment. 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). 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. Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.
Substances chimiques
Anti-HIV Agents
0
Reverse Transcriptase Inhibitors
0
Rilpivirine
FI96A8X663
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1930-1939Informations de copyright
© 2020 British Pharmacological Society.
Références
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