Clinical trial NCT00495326: Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146 CARINEMO)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Tuberculosis
Aids
Hiv Infections
Keywords: drug interactions
Treatment Naive
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
Collaborators: name: Medecins Sans Frontieres, Netherlands
First posted: 2007-07-03
Enrollment: 570
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.)
timeFrame: 3, 6 and 12 months
Secondary outcomes:
measure: New or recurrent stage 3 or 4 HIV/AIDS related events
timeFrame: 12 months
measure: Deaths after one year
timeFrame: 12 months
measure: Severe drugs side effects
timeFrame: 12 months
measure: Immune Reconstitution Syndrome(IRIS)
timeFrame: 12 months
measure: Increase of CD4 cell count induced by HAART
timeFrame: at 6 months and 1 year
measure: Pharmacokinetic profile of nevirapine when combined with rifampicin
timeFrame: 2 months
measure: Rifampicin plasma concentration dosage
timeFrame: 2 months
Other outcomes:
Locations:
city: Maputo
country: Mozambique
facility: Health centre of Alto Mae, Chamanculo district
city: Maputo
country: Mozambique
facility: Health centre of Josue Macao
city: Maputo
country: Mozambique
facility: Health centre of Malavane
Study officials:
affiliation: Epicentre
name: Maryline Bonnet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ministry of Health, Instituto Nacional de Saude, Mozambique
name: Nilesh Bhatt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bhatt NB, Barau C, Amin A, Baudin E, Meggi B, Silva C, Furlan V, Grinsztejn B, Barrail-Tran A, Bonnet M, Taburet AM; ANRS 12146-CARINEMO Study Group. Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment. Antimicrob Agents Chemother. 2014 Jun;58(6):3182-90. doi: 10.1128/AAC.02379-13. Epub 2014 Mar 24.
citation: Bonnet M, Bhatt N, Baudin E, Silva C, Michon C, Taburet AM, Ciaffi L, Sobry A, Bastos R, Nunes E, Rouzioux C, Jani I, Calmy A; CARINEMO study group. Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial. Lancet Infect Dis. 2013 Apr;13(4):303-12. doi: 10.1016/S1473-3099(13)70007-0. Epub 2013 Feb 20.