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

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase: Completed; Phase 3; Phase 2

Conditions: Tuberculosis; Hiv Infections; Aids

Treatments: Drug: Nevirapine based therapy; Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z); Drug: Efavirenz based therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00495326

ANRS 12146 CARINEMO

Details and patient eligibility

About

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.

Full 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.

Enrollment: 570 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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570 participants in 2 patient groups

1

Experimental group

Description:

Nevirapine-based ART

Treatment:

Drug: Nevirapine based therapy

Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)

2

Active Comparator group

Description:

Efavirenz-based ART

Treatment:

Drug: Efavirenz based therapy

Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)