Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146 CARINEMO)

Phase 2

Completed

• Conditions: Tuberculosis; Aids; Hiv Infections
• Interventions: Drug: Nevirapine based therapy; Drug: Efavirenz based therapy; Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)

• Registration Number: NCT00495326
• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

Brief Summary

The purpose of this study is to determine whether the use of Nevirapine in HIV patients already treated against tuberculosis by Rifampicin is as efficient and as well tolerated as Efavirenz.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2007-07-02
• Study First Submitted QC: 2007-07-02
• Study First Posted: 2007-07-03
• Study Start: 2007-12
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-14
• Last Update Posted: 2012-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 570

Inclusion Criteria

• Person HIV infected
• Aged of 18 years or more
• Signed informed consent
• New case of tuberculosis: patient who never received TB treatment or for less than 1 month
• Patients receiving rifampicin based TB regimen since 4 to 6 weeks
• CD4 cell count < 250 cell/mm3 in the 4 weeks following the TB diagnosis
• Naïve of HAART
• For women of childbearing age, to have a negative plasmatic test for pregnancy and to accept to take a contraception or declare no wish of pregnancy in the coming year.

Exclusion Criteria

• To have a positive plasmatic test for pregnancy
• Karnofsky score <60%
• ALAT > 4N (Hepatitis grade 3 or 4)
• Ongoing psychiatric pathology
• Refuse to participate in the study

Amendment :

• bilirubin > grade 3
• any grade 4 clinical sign or biological result at time of inclusion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Nevirapine based therapy	Nevirapine-based ART
2	Efavirenz based therapy	Efavirenz-based ART
2	Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)	Efavirenz-based ART
1	Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)	Nevirapine-based ART

Primary Outcome Measures

Name	Time	Method
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.)	3, 6 and 12 months

Secondary Outcome Measures

Name	Time	Method
New or recurrent stage 3 or 4 HIV/AIDS related events	12 months
Deaths after one year	12 months
Severe drugs side effects	12 months
Immune Reconstitution Syndrome(IRIS)	12 months
Increase of CD4 cell count induced by HAART	at 6 months and 1 year
Pharmacokinetic profile of nevirapine when combined with rifampicin	2 months
Rifampicin plasma concentration dosage	2 months

Trial Locations

Locations (3)

Health centre of Josue Macao; 🇲🇿 Maputo, Mozambique

Health centre of Malavane; 🇲🇿 Maputo, Mozambique

Health centre of Alto Mae, Chamanculo district; 🇲🇿 Maputo, Mozambique