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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: efavirenz; Drug: tenofovir DF; Drug: emtricitabine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Service des maladies Infectieuses et tropicales Hopital Necker-Enfants Malades

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Principal Investigator: Olivier Lortholary, MD, Hopital Necker-Enfants Malades; Study Director: Geneviève Chêne, MD, INSERM U593

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: June 23, 2005
• First Submitted That Met QC Criteria: June 23, 2005
• First Posted (Estimate): June 24, 2005

Study Record Updates

• Last Update Posted (Estimate): December 22, 2011
• Last Update Submitted That Met QC Criteria: December 21, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: HIV infections; Treatment Naive; tuberculosis; tuberculosis agents; Anti HIV agents
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; HIV Infections; Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; 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; Tenofovir; Emtricitabine; Efavirenz
• Other Study ID Numbers: 2005-002470-30; ANRS129 BKVIR