Raltegravir Versus Efavirenz in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis (REFLATE TB2)

ANRS, Emerging Infectious Diseases

Status and phase

Completed

Phase 3

Conditions

Tuberculosis

HIV-1 Infection

Treatments

Drug: Tenofovir + lamivudine + raltegravir

Drug: Tenofovir + lamivudine + efavirenz

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02273765

ANRS 12300 REFLATE TB2

Details and patient eligibility

About

Phase III trial evaluating raltegravir as an alternative to efavirenz for antiretroviral treatment of HIV-infected patients with tuberculosis.

Full description

Phase III multicenter, international, open-label, randomized trial evaluating non-inferiority of raltegravir at dose of 400mg BID compared to efavirenz 600mg QD, both in association with tenofovir disoproxil fumarate and lamivudine in ART-naïve HIV-1 infected patients with active TB disease receiving a rifampin-based TB treatment initiated <8 weeks before inclusion. Patients will be randomized between 2 arms: the raltegravir (RAL) 400 mg bid arm or the efavirenz (EFV) 600 mg qd arm, each in combination with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) and will be followed for 48 weeks after entry in the trial (ART initiation).

Enrollment

460 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed informed consent form
Aged 18 years or more
Confirmed HIV-1 infection as documented at any time prior to trial entry per national HIV testing procedures
ART naïve
For women of childbearing potential i.e. women of childbearing age who are not menopausal, or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or not refraining from sexual activity: negative urinary test for pregnancy and acceptance to use contraceptive methods
Confirmed or probable active TB disease of any location, except neurological (meningitis or encephalitis), according to the following criteria based on WHO updated definitions:
- Bacteriologically confirmed pulmonary TB (PTB) or extrapulmonary TB (EPTB), e.g. TB with a biological specimen positive by smear microscopy, culture or nucleic acid amplification test (such as Xpert MTB/RIF).
- Clinically diagnosed PTB or EPTB with typical histological evidence of TB (caseous or granulomatous) on biopsy specimen or positive urinary LAM test OR a significant improvement on TB treatment
Ongoing standard rifampin-containing TB treatment for ≤8 weeks at inclusion
For French patients, affiliation to a Social Security program

Exclusion criteria

HIV-2 co-infection
Impaired hepatic function (icterus or ALT (SGPT) > 5ULN)
Hemoglobin < 6.5 g/dl
Creatinine clearance <60ml/min (assessed by the Cockroft and Gault formula)
Mycobacterium tuberculosis strain resistant to rifampin (current or past history).
Neurological TB (meningitis or encephalitis)
Severe associated diseases requiring specific treatment (including all specific AIDS defining illnesses other than TB, and any severe sepsis)
Any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to trial procedures including very severe TB-related clinical condition
Concomitant treatments including phenytoin or phenobarbital (compounds interacting with UGT1A1)
For HCV co-infected patients, need to start specific treatment for hepatitis during the trial duration
For women of childbearing potential:
- Pregnancy or breastfeeding
- Refusal to use a contraceptive method
- Any history of ARV intake for prevention of mother to child transmission of HIV (pMTCT)
Subjects participating in another clinical trial evaluating therapies and including an exclusion period that is still in force during the screening phase
Person under guardianship, or deprived of freedom by a judicial or administrative decision