Clinical trial NCT00115609: Efficacy of Tenofovir-Emtricitabine and Efavirenz in HIV Infected Patients With Tuberculosis (ANRS129)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Tuberculosis
Keywords: HIV infections
tuberculosis
tuberculosis agents
Anti HIV agents
Treatment Naive
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-06-24
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: treatment success rate at week 48 (W48)
timeFrame: W48
Secondary outcomes:
measure: course of plasma HIV-1 RNA between W0 and W48
timeFrame: W48
measure: tuberculosis cure rate
timeFrame: W48
measure: safety of trial treatments (number of events, description, time to onset, metabolic disorders, immune restoration syndrome)
timeFrame: W48
measure: frequency of treatment changes or discontinuations
timeFrame: W48
measure: clinical progression of HIV infection
timeFrame: W48
measure: course of CD4 and CD8 T lymphocytes
timeFrame: W48
measure: study of resistance in the case of virological failure
timeFrame: W48
measure: study of compliance and quality of life
timeFrame: W48
measure: pharmacokinetic study of tuberculostatic agents
timeFrame: W02,W08,W12, W24
measure: effect of treatment on hepatitis B viral replication
timeFrame: W48
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des maladies Infectieuses et tropicales Hopital Necker-Enfants Malades
Study officials:
affiliation: Hopital Necker-Enfants malades
name: Olivier Lortholary, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM U593
name: Geneviève Chêne, MD
role: STUDY_DIRECTOR
References: