Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146 CARINEMO) (CARINEMO)
|Tuberculosis Aids Hiv Infections||Drug: Nevirapine based therapy Drug: Efavirenz based therapy Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Randomized Non-inferiority Trial Comparing the Nevirapine-based Antiretroviral Therapy Versus the Standard Efavirenz-based ART for the Treatment of HIV-TB Co-infected Patients on Rifampicin-based Therapy (ANRS 12146 CARINEMO)|
- Viral load measure (Virological failure will be defined after 2 consecutive measures as : More than 1 log10 increase in plasma HIV-1 RNA concentration for patients with detectable viral load (> 50 copies/mL) at the previous dosage.) [ Time Frame: 3, 6 and 12 months ]
- New or recurrent stage 3 or 4 HIV/AIDS related events [ Time Frame: 12 months ]
- Deaths after one year [ Time Frame: 12 months ]
- Severe drugs side effects [ Time Frame: 12 months ]
- Immune Reconstitution Syndrome(IRIS) [ Time Frame: 12 months ]
- Increase of CD4 cell count induced by HAART [ Time Frame: at 6 months and 1 year ]
- Pharmacokinetic profile of nevirapine when combined with rifampicin [ Time Frame: 2 months ]
- Rifampicin plasma concentration dosage [ Time Frame: 2 months ]
|Study Start Date:||December 2007|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Drug: Nevirapine based therapy
Other Name: TriomuneDrug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
Active Comparator: 2
Drug: Efavirenz based therapy
Efavirenz EFV 200 mg (3 tablets/d) Lamivudine 3TC 300mg (2 tablets of 150mg/d) D4T generic 30mg or 40mg (2 tablets/d)
Other Names:Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
Anti Retroviral Therapy (ART) reduces tuberculosis (TB) incidence in HIV-infected patients and reduces mortality among TB patients with deep immune suppression. The Fixed Drug Combination (FDC) nevirapine (NVP)-lamivudine-stavudine is the first line ART available for low-income countries. Rifampicin (RMP), due to its liver induction effect, reduces significantly NVP plasma concentration, raising concerns regarding the risk of resistance and subsequent treatment failure. Therefore, in co-infected patients, WHO recommends delaying ART or using efavirenz (EFV)-based ART. Although EFV is also reduced at lower level, longitudinal studies report good efficacy and safety when given concomitantly with RMP.
In low-income countries, poor access to EFV, contradiction during pregnancy and absence of FDC containing EFV lead to difficulties in HIV-TB treatment.
Despite 2 limited retrospective studies and a non-randomised prospective study, which report good virological response at 6 months in co-infected patients receiving NVP and RMP co-administration, existing data are too limited to change the recommendation.
The aim of the study is to compare, in terms of therapeutic efficacy and clinical safety, the nevirapine-based HAART to the standard efavirenz-based HAART, in HIV/TB co-infected patients receiving a rifampicin-based TB treatment.
The study will evaluate one year after TB treatment initiation, whether the HAART efficacy (virological outcome, death or lost of follow-up) induced by NVP-based HAART is non-inferior to those induced by EFV based HAART, in patients receiving concomitantly HAART and RMP-based TB treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00495326
|Health centre of Alto Mae, Chamanculo district|
|Health centre of Josue Macao|
|Health centre of Malavane|
|Principal Investigator:||Maryline Bonnet, MD||Epicentre|
|Principal Investigator:||Nilesh Bhatt, MD||Ministry of Health, Instituto Nacional de Saude, Mozambique|