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

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.

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