Modification of Doses of Efavirenz According to Its Blood Concentration in HIV Patients

Open, Parallel and Randomised Pilot Clinical Trial to Evaluate the Utility of the Therapeutic Monitoring of Plasma Levels of Efavirenz in Hiv-Infected Patients Initiating an Antiretroviral Treatment Regimen With Sustiva

This is a study on the utility of the modification of doses of efavirenz guided by its plasma concentration (therapeutic drug monitoring) in HIV-infected patients initiating treatment with Sustiva.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Efavirenz capsules 200 mg and 600 mg

Detailed Description

Currently, efavirenz is dosed systematically, without taking into account the individual characteristics of each individual patient. However, plasma concentration of efavirenz may widely vary between different subjects that receive the same dose of the drug (interindividual variability).

Therapeutic drug monitoring (TDM) signifies individualised pharmacological dosing, based on the plasma levels that each patient presents. This strategy has been broadly used in the field of the treatment of other medical conditions and is acquiring growing interest in the field of antiretroviral treatment. Thus, the use of TDM for the treatment of naïve patients with nelfinavir or with indinavir has translated into an increase in the proportion of individuals with suppressed viral load and also into a reduction in HAART-induced adverse events . However, data on the utility of the therapeutic monitoring of the levels of efavirenz in HIV-infected patients are very scant.

On the basis of the above, it might be thought that the modification of the doses of efavirenz, guided by its plasma concentration, in patients receiving this drug and whose plasma levels of efavirenz are outside the therapeutic range, might improve the tolerability of the treatment without compromising virological efficacy.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias I Pujol Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 patients.
• According to the criteria of the treating physician, the need to initiate a regimen of antiretroviral treatment that includes efavirenz (both antiretroviral-naive patients and others on treatment with protease inhibitors switching to efavirenz for salvage reasons or for simplification of the anti-retroviral therapy are included).
• Absence of opportunistic infections and/or tumours in the three months prior to inclusion.

Exclusion Criteria:

• History of allergic hypersensitivity to the investigational drug.
• History of previous failure with antiretroviral treatment with non-nucleoside reverse transcriptase inhibitors or previously documented resistance to efavirenz
• History of psychiatric comorbidity which, in the investigator's opinion, renders the use of efavirenz inadvisable.
• Active consumption of alcohol (>50 g/day) or other illegal drugs (except cannabis)
• Suspicion of unsuitable compliance with the antiretroviral treatment.
• Pregnant women or breast-feeding mothers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Efavirenz capsules 600 mg
Experimental: Experimental; Modification of doses of efavirenz guided by its plasma concentration (therapeutic drug monitoring)	Drug: Efavirenz capsules 200 mg and 600 mg; Modification of doses of efavirenz guided by its plasma concentration (therapeutic drug monitoring); Other Names: Sustiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients who need to interrupt treatment with efavirenz due to virological failure	after 96 weeks of follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients who need to interrupt treatment with efavirenz due to adverse side effects	after 96 weeks of follow-up
To determine the incidence of adverse events and the toxicity profile (haemogram, AST/ALT/FA/GGT, creatinine, urea)	during the 96 weeks of follow-up
To evaluate the proportion of patients with plasma levels of efavirenz between 1.0 and 4.0 mg/L	during the 96 weeks of follow-up
To evaluate the relationship between the appearance of secondary events during treatment with efavirenz and the patients' demographic and clinical characteristics, as well the plasma concentration of efavirenz	during the 96 weeks of follow-up
To evaluate the variations in CD4 and CD8 lymphocyte count	during the 96 weeks of follow-up

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Investigators: Principal Investigator: Bonaventura Clotet, MD, PhD, Lluita Sida Foundation-HIV Unit

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 3, 2006
• First Submitted That Met QC Criteria: March 3, 2006
• First Posted (Estimate): March 6, 2006

Study Record Updates

• Last Update Posted (Actual): February 14, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: HIV; Therapeutic drug monitoring; Treatment Experienced; Treatment Naive
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz
• Other Study ID Numbers: startTDM-EFV; 2005-002493-30

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No