Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2009-04-30

Brief Summary

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Background

Low concentrations of protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) are associated with an increased risk of virological failure. Likewise, excessive antiretroviral drug concentrations increase the risk of toxicity. Therapeutic drug monitoring (TDM) may identify and correct excessively high or low PI and/or NNRTI concentrations, and thus minimize toxicity and risk of treatment failure. Treatment guidelines only recommend using TDM to help optimize ARV therapy in selected patients, and there are no clear recommendations to guide the clinician who decides to adjust drug doses. Prospective studies have demonstrated the relationship between EFV plasma concentration and neuropsychiatric symptoms. Moreover, EFV is metabolized mainly by cytochrome P450 2B6 and its concentration was reported to be associated with the CYP2B6 516GrT genetic polymorphism.

For drugs such as EFV or LPV/r, lower doses than the ones validated for standard clinical use have demonstrated efficacy in dose-ranging studies.

The investigators will use a standardised algorithm to reduce doses in patients with plasma EFV or LPV/r concentration above percentile 75. This algorithm is based on a Bayesian approach from the pharmacology unit in Lausanne. The investigators hypothesize that a dosage individualisation is feasible and safe.

2.2 Study Aims

The investigators aim at testing a simplified algorithm for dose reduction in patients with documented virological efficacy, treated by a stable LPV/r or EFV based regimen with elevated plasma concentration of these drugs.

Study Design

Prospective open label study in which all eligible patients screened with a plasma drug concentration of either EFV or LPV/r above percentile 75 will be included. After confirmation of the results at baseline, patients will be offered to decrease drug dosage by a third or a half according to a standardised algorithm. All patients will undergo HIVRNA, biochemistry and validated questionnaires after 3 and 6 months to assess the safety and the benefit of this strategy.

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Detailed Description

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Conditions

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Human Immunodeficiency Virus HIV Infections

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LPV

Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (\>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.

Group Type EXPERIMENTAL

Reducing dose of Lopinavir

Intervention Type DRUG

Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (\>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.

EFV

Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (\>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.

Group Type EXPERIMENTAL

Reducing dose of efavirenz

Intervention Type DRUG

Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (\>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.

Interventions

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Reducing dose of Lopinavir

Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (\>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.

Intervention Type DRUG

Reducing dose of efavirenz

Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (\>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Stable regimen including either EFV or LPV/r
* HIVRNA below 40 copies since at least 3 months
* Antiretroviral drug concentration (EFV, LPV/r) plasma concentration at screening above P75
* Signed consent for the SHCS genetics core project

Exclusion Criteria

* Concomitant medication:Amiodarone, bepidril, flecainide, propafenone, quinidine,Astemizole, terfenadine,Dihydroergotamine, ergotamine,Midazolam, triazolam,Cisapride,Pimozide,Rifabutin
* Renal or hepatic impairment
* Pregnancy or wish to become pregnant within the next 6 months
* Both EFV and LPV/r as part of the antiretroviral drug regimen

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No