Efficacy and Safety of 2 Raltegravir Doses in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

Phase II Open-label Randomized Multicenter Trial to Compare the Efficacy and Safety of Two Different Doses of Raltegravir and Efavirenz, All in Combination With Tenofovir and Lamivudine, in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

Raltegravir is a potent antiretroviral agent that could be used as an alternative to efavirenz in HIV-1 infected patients with tuberculosis. However due to pharmacokinetic interactions, the optimal dose of raltegravir to be used in combination with rifampin is currently unknown.

This phase II open-label randomized multicenter trial is designed to estimate the antiviral efficacy of two doses of raltegravir and one dose of efavirenz at week 24, in HIV-1 naive patients co-infected with active tuberculosis (TB) treated with rifampin.

Inclusion Criteria:

• Adult patients (at least 18 years old)
• Plasma HIV RNA > 1000 copies/ml
• HIV-1-infection confirmed by ELISA and Western blot or Immunofluorescence
• ART naïve patients or
• ART for less than 3 months and more than 6 months ago ; an HIV resistance genotype at baseline showing no mutation to NNRTI and TDF or 3TC will be required
• For women of childbearing age, negative urinary test for pregnancy and to accept contraceptive methods: condom use and intra-uterine device when possible or declare no wish of pregnancy in the coming year.
• Confirmed or probable TB
• TB treatment including rifampin started since 2 to 8 weeks before randomisation
• Signed informed consent form
• For French patients, to be affiliated to the National Health Care System

Exclusion Criteria:

• HIV-2 infection (single or with HIV-1)
• Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception
• ALT>2.5N, Hb <7g/dl, neutrophils < 750/mm3, platelet<50 000/mm3, bilirubin >5N, lipase >3N
• Creatinine clearance <60ml/min as assessed by the Cockcroft method
• Ongoing psychiatric pathology or any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol
• Concomitant treatments including phenytoin or phenobarbital (compounds interacting with UGT1A1)
• Prior TB with a Mycobacterium tuberculosis strain resistant to rifampin
• TB treatment started for more than 8 weeks before randomisation