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Concentration–response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients
- Source :
- Journal of Antimicrobial Chemotherapy, Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2019, 74 (7), pp.1992-2002. ⟨10.1093/jac/dkz141⟩, Journal of Antimicrobial Chemotherapy, 2019, 74 (7), pp.1992-2002. ⟨10.1093/jac/dkz141⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 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. Objectives To develop the first pharmacodynamic model of rilpivirine in order to establish the rilpivirine concentration–response relationship for future treatment optimization. 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. 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. 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.
- Subjects :
- Microbiology (medical)
Oncology
Adult
Male
medicine.medical_specialty
Anti-HIV Agents
[SDV]Life Sciences [q-bio]
Population
HIV Infections
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Emtricitabine
030226 pharmacology & pharmacy
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Pharmacokinetics
Internal medicine
medicine
Humans
Pharmacology (medical)
Trough Concentration
Computer Simulation
030212 general & internal medicine
education
Aged
Pharmacology
education.field_of_study
business.industry
Rilpivirine
Disease Management
Middle Aged
Models, Theoretical
Viral Load
3. Good health
CD4 Lymphocyte Count
Regimen
Infectious Diseases
chemistry
Pharmacodynamics
HIV-1
Female
Drug Monitoring
business
Viral load
Algorithms
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 03057453 and 14602091
- Database :
- OpenAIRE
- Journal :
- Journal of Antimicrobial Chemotherapy, Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2019, 74 (7), pp.1992-2002. ⟨10.1093/jac/dkz141⟩, Journal of Antimicrobial Chemotherapy, 2019, 74 (7), pp.1992-2002. ⟨10.1093/jac/dkz141⟩
- Accession number :
- edsair.doi.dedup.....a065712ddc9cdfe2d027b27f76c411ea