Clinical trial NCT00836212: Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring
Official title: Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Human Immunodeficiency Virus
HIV Infections
Keywords: HIV
Adjusting Antiretroviral Therapy
Dosage using Therapeutic Drug Monitoring
Swiss HIV Cohort Study
HIV Geneva
lopinavir
efavirenz
Treatment Experienced
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Swiss HIV Cohort Study
First posted: 2009-02-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients who reach a plasma concentration within targets (P25-P75) after at least one cycle (and maximum two cycles) of dose reduction according to the provided algorithm at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Number of patients who reach a plasma concentration within targets (P25-P75) after at least one cycle of dose reduction -percentage of spared drugs through TDM-guided dosage adaptation over a 6 months period. Compliance: electronic pills count
timeFrame: 6 months
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: University Hopistal of Geneva
Study officials:
affiliation: University Hospital, Geneva
name: Alexandra AC Calmy
role: PRINCIPAL_INVESTIGATOR
References: