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Concentration-response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2019 Jul 01; Vol. 74 (7), pp. 1992-2002. - Publication Year :
- 2019
-
Abstract
- Background: Rilpivirine is widely prescribed in people living with HIV. Although trough plasma concentrations have been associated with virological response, the drug pharmacodynamics remain incompletely characterized.<br />Objectives: To develop the first pharmacodynamic model of rilpivirine in order to establish the rilpivirine concentration-response relationship for future treatment optimization.<br />Methods: A retrospective observational study was conducted in patients receiving the once-daily rilpivirine/tenofovir disoproxil fumarate/emtricitabine regimen. Individual rilpivirine trough plasma concentrations over time were predicted using a previous pharmacokinetic model. An established susceptible, infected, recovered model was used to describe HIV dynamics without assuming disease steady-state. Population analysis was performed with MONOLIX 2018 software. Simulations of the viral load evolution as a function of time and rilpivirine trough plasma concentration were performed.<br />Results: Overall, 60 naive and 39 pre-treated patients were included with a follow-up ranging from 2 to 37 months. The final model adequately described the data and the pharmacodynamic parameters were estimated with a good precision. The population typical value of rilpivirine EC50 was estimated at 65 ng/mL. A higher infection rate constant of CD4 cells for HIV-1 was obtained in pre-treated patients. Consequently, the time to obtain virological suppression was longer in pre-treated than in naive patients.<br />Conclusions: The concentration-response relationship of rilpivirine was satisfactorily described for the first time using an original population pharmacodynamic model. Simulations performed using the final model showed that the currently used 50 ng/mL rilpivirine trough plasma concentration efficacy target might need revision upwards, particularly in pre-treated patients.<br /> (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Algorithms
Anti-HIV Agents therapeutic use
CD4 Lymphocyte Count
Computer Simulation
Disease Management
Drug Monitoring
Female
HIV Infections immunology
Humans
Male
Middle Aged
Rilpivirine therapeutic use
Viral Load
Young Adult
Anti-HIV Agents pharmacokinetics
HIV Infections drug therapy
HIV Infections virology
HIV-1 drug effects
Models, Theoretical
Rilpivirine pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 74
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 31225609
- Full Text :
- https://doi.org/10.1093/jac/dkz141