Raltegravir Versus Efavirenz in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

Phase III Open-label Randomized Multicenter Trial to Assess the Non-inferiority of Raltegravir Compared With EFavirenz, Both in Combination With LAmivudine and TEnofovir, in ART-naïve HIV-1-infected Patients Receiving Rifampin for Active TuBerculosis

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

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).

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