Randomized Clinical Trial to Assess the Efficacy and Safety of Concomitant Use of Rifampicin and Efavirenz 600 X 800mg

Study Overview
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Brief Summary
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Rifampicin is a potent inducer of the CYP450 and decrease the plasmatic concentration of NNRTI and Protease Inhibitors. In our study we are going to compare the 600 an 800mg doses of efavirenz concomitant of rifampicin use to treat tuberculosis. The hypothesis is that the 800 mg dose would be more adequate than the 600mg

Detailed Description
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The study consist in a open label randomized clinical trial comparing efavirenz 600mg QID versus efavirenz 800mg QID in patients with tuberculosis (treated with regimens including rifampicin) and AIDS diagnosis. The total duration of the study is 6 months for each patient. All eligible patient will be treated with a fist line regimen for tuberculosis according to Brazilian guidelines: rifampicin (600mg QID); isoniazid (400mg QID) e pyrazinamide (2g QID) during 6 months for a weight of 45 kg or more and adapted doses for persons with less than 45 kg. For patients with previous history of TB therapy etambutol 1.200mg QID will be added to the regimen. Both groups will receive nucleoside reverse transcriptase inhibitors (NRTI)and a non nucleoside transcriptase inhibitor (NNRTI) to treat HIV. The ITRN of first choice will be zidovudine and lamivudine association. Patients presenting contra indication for the use of those drugs will receive others NRTI. The NNRTI is efavirenz (800 or 600mg). Antiretrovirals will be initiated 30 days after stable TB therapy. In case of adverse events during TB therapy that lead to treatment interruption, the study drugs will be delayed until the 30th day after triple therapy for TB. During HIV therapy NRTI can be changed in case of intolerance

Official Title
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Anti-retroviral Efficacy, Tolerance and Other Pharmacologic Interactions of the Non Nucleoside Analog Efavirenz in Association With Rifampicin to Treat Tuberculosis and AIDS

Conditions
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Tuberculosis, HIV Infections

Intervention / Treatment
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* Drug: efavirenz


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with tuberculosis diagnosis, HIV positive. Agreement to avoid not allowed drugs during the trial, agreement to participate in the study (informed consent) Exclusion Criteria: Active liver disease Pregnancy or breast feeding CD4 counts >350

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EFAVIRENZ 800mg<br>Efavirenz 800 mg (tablet) PO QD during 5 months associated with two nucleoside analogs during tuberculosis therapy with rifampicin | Drug: efavirenz<br>* 600mg X 800mg QID during TB therapy with rifampicin associated with other antituberculosis drugs in patients concomitant treated for tuberculosis and AIDS<br>* Other names: Sustiva;|
| Active Comparator: EFAVIRENZ 600mg<br>Efavirenz 600 mg (tablet) PO QD during 5 months associated with two nucleoside analogs during tuberculosis therapy with rifampicin | Drug: efavirenz<br>* 600mg X 800mg QID during TB therapy with rifampicin associated with other antituberculosis drugs in patients concomitant treated for tuberculosis and AIDS<br>* Other names: Sustiva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with viral load < 80 at the end of tuberculosis therapy proportion of adverse events in each group |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic reconstitution Genotyping resistance |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efavirenz, tuberculosis, AIDS, rifampicin, efficacy, safety, Treatment Naive