This study will assess and characterize the variability observed in the response to darunavir therapy, an antiretroviral medication used against the Human Immunodeficiency Virus (HIV). More specifically, it aims to quantify variations in the drug's blood concentrations and determine the sources of such variability, both genetic and non-genetic. In light of this information, current dosage guidelines will then be reviewed.
Data will be used to create a population pharmacokinetic model. Inter- and intra-individual pharmacokinetic variability will be quantified and linked to patient-specific covariates, both genetic and non-genetic in nature. Pharmacokinetic-pharmacodynamic relationships will be established, linking drug exposure to efficacy (as measured by CD4 cell count and viral load reduction) and toxicity (as measured by frequency and degree of adverse events). Simulations will be conducted for specific patient profiles and current dosage guidelines reviewed. Pharmacokinetic design : combined sparse/intensive sampling * Sparse sampling : One blood sample collected in each individual at a random post-intake time (during a routine visit to the hospital), up to three times over the course of the study period (months 1-18). * Intensive sampling : Eight blood samples collected over six hours in a subset of twelve individuals (during an additional observation period, months 19-22).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
127
The investigated drugs are Prezista (darunavir 600 mg twice-daily or 800 mg once-daily) and Rezolsta (darunavir 800 mg/cobicistat 150 mg once-daily)
Cliniques universitaires Saint-Luc
Brussels, Belgium
Darunavir clearance
Assessment of darunavir whole-body clearance and inter-compartmental clearance through population pharmacokinetic methods
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir volume of distribution
Assessment of darunavir volume of distribution through population pharmacokinetic methods
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir absorption rate
Assessment of darunavir absorption rate through population pharmacokinetic methods
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir area under the concentration-time curve (AUC)
Assessment of darunavir area under the concentration-time curve through population pharmacokinetic methods
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir maximum plasma concentration (Cmax)
Assessment of darunavir maximum plasma concentration through population pharmacokinetic methods
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Frequency of adverse events/laboratory abnormalities
Assessment of the frequency of adverse events or laboratory abnormalities
Time frame: Up to 18 months
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Change in viral load
Assessment of the change in viral load (HIV copies/ml of blood)
Time frame: Up to 18 months
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
Assessment of the change in blood CD4+ T lymphocyte count
Time frame: Up to 18 months
Ritonavir/cobicistat AUC
Assessment of the pharmacokinetic booster (either ritonavir or cobicistat, depending on the subject) AUC through population pharmacokinetic methods
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)