Optimization of Darunavir Therapy and Dosage Recommendations

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Optimization of Darunavir Therapy Through Population Pharmacokinetic Modeling, Simulations and Dosage Guidelines

Conditions
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Human Immunodeficiency Virus I Infection

Intervention / Treatment
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* Drug: Darunavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving informed consent HIV-positive Routinely followed at the Cliniques universitaires Saint-Luc Treated with darunavir Inclusion Criteria (intensive sampling): - Perfect adherence to treatment (as assessed by anamnesis and based on available PK data for each patient) Exclusion Criteria: - N/A

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Darunavir<br>All patients treated with darunavir | Drug: Darunavir<br>* 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)<br>* Other names: Rezolsta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Darunavir clearance | Assessment of darunavir whole-body clearance and inter-compartmental clearance through population pharmacokinetic methods | 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 | 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 | 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 | 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 | Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events/laboratory abnormalities | Assessment of the frequency of adverse events or laboratory abnormalities | Up to 18 months | 
| Change in viral load | Assessment of the change in viral load (HIV copies/ml of blood) | 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 | 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 | Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period) |