Efficacy of Tenofovir-Emtricitabine and Efavirenz in HIV Infected Patients With Tuberculosis (ANRS129)

Study Overview
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Brief Summary
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Successful therapy of both tuberculosis and HIV disease share similar problems: pill burden, drug interaction, adherence challenge and toxicity. This study will test the efficacy and safety of a once daily antiretroviral regimen in HIV-tuberculosis coinfected patients.

Detailed Description
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The proposed research consists of conducting a pilot trial BKVIR designed to answer the question of whether once daily tenofovir-emtricitabine-efavirenz triple-agent therapy is effective and well tolerated when it must be initiated within three months after initiation of a three-agent or four-agent tuberculostatic therapy in antiretroviral-naive HIV-infected patients. As the proposed pilot trial comprises the initiation of antiretroviral therapy during the three months following the initiation of tuberculostatic therapy, we propose to set up systematic, continuous registration of HIV-infected patients with a diagnosis of tuberculosis in participating centers during the study period in order to evaluate their eligibility for inclusion in the pilot trial. The initial declaration phase in the register, in addition to facilitating inclusions in the pilot trial, should also allow: 1) a better understanding of the reasons for non-inclusion in the trial, allowing the eligibility criteria to be adjusted if necessary during the trial; and 2) to describe the antiretroviral therapies used during co-infection and their time of initiation in relation to tuberculostatic therapy. This research is expected to contribute to an updating of the treatment guidelines in the context of tuberculosis in HIV-infected patients. The data collected will constitute a unique database on this issue not only in France, but also internationally, which will also be useful to optimize management strategies of these two diseases in developing countries.

Official Title
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Pilot Trial Evaluating Once Daily Triple Combination Antiretroviral Therapy With Tenofovir-Emtricitabine and Efavirenz in HIV-1 Infected Patients With Mycobacterium Tuberculosis Infection ANRS129 BKVIR

Conditions
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HIV Infections, Tuberculosis

Intervention / Treatment
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* Drug: efavirenz
* Drug: tenofovir DF
* Drug: emtricitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years Infected by HIV-1 Naive to antiretroviral therapy Presenting an indication to start antiretroviral therapy (according to the recommendations of the Delfraissy 2004 report) Histologically or microbiologically confirmed tuberculosis Receiving tuberculostatic therapy for less than three months Exclusion Criteria: Isolated HIV-2 infection Neoplasm treated by chemotherapy and/or radiotherapy Pregnancy or plans for pregnancy Breastfeeding Contraindication to one of the antiretroviral drugs Atypical mycobacterial infection Hemoglobin below 8 g/dL Neutrophils below 750/mm3 Platelets below 50,000/mm3 Creatinine clearance below 60 ml/min Alkaline phosphatase, ASAT, ALAT or bilirubin over 3 times the upper limit of normal

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: efavirenz|800mg for patients treated by rifampicine 600mg for other patients|
|Drug: tenofovir DF|300mg once a day|
|Drug: emtricitabine|one pill of 200mg once a day|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment success rate at week 48 (W48) |  | W48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| course of plasma HIV-1 RNA between W0 and W48 |  | W48 | 
| tuberculosis cure rate |  | W48 | 
| safety of trial treatments (number of events, description, time to onset, metabolic disorders, immune restoration syndrome) |  | W48 | 
| frequency of treatment changes or discontinuations |  | W48 | 
| clinical progression of HIV infection |  | W48 | 
| course of CD4 and CD8 T lymphocytes |  | W48 | 
| study of resistance in the case of virological failure |  | W48 | 
| study of compliance and quality of life |  | W48 | 
| pharmacokinetic study of tuberculostatic agents |  | W02,W08,W12, W24 | 
| effect of treatment on hepatitis B viral replication |  | W48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti HIV agents, HIV infections, tuberculosis, tuberculosis agents, Treatment Naive