Efficacy and Safety of 2 Raltegravir Doses in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis
- Registration Number
- NCT00822315
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 155
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 efavirenz efavirenz 2 raltegravir raltegravir 400 mg 3 raltegravir raltegravir 800 mg
- Primary Outcome Measures
Name Time Method Virologic success, using Time to Loss of Virologic Response (TLOVR) algorithm: -Plasma HIV RNA below 50 copies/ml at week 20, confirmed at week 24 -Absence of permanent treatment discontinuation -Absence of death -Still follow-up at week 24 24 weeks
- Secondary Outcome Measures
Name Time Method Proportion of patients with virologic response with the following definitions: - Plasma HIV RNA <50 copies/ml at week 24 - Rate of strategy discontinuation and treatment changes - Proportion of death - Proportion of patients loss to follow-up 24 weeks Rate of viral resistance mutations in the plasma at the time of virologic failure and in comparison with HIV-RNA mutations at W0 At the time of virologic failure Proportion of patients with virologic response with the following definitions: o Plasma HIV RNA <50 copies/ml o Plasma HIV RNA <400 copies/ml 24 and 48 weeks Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48 48 weeks Evolution of CD4 cell counts from baseline to week 48 48 weeks Frequency, type and time to a new AIDS-defining event or death Through out the trial Anti-TB resistance rate 48 weeks Evolution of raltegravir and efavirenz trough concentration Through out the trial Frequency, type, time to grade 3 or 4 adverse event Through out the trial Rate of success of TB treatment 48 weeks
Trial Locations
- Locations (9)
Ipec/Fiocruz
🇧🇷Rio de Janeiro, Brazil
Hospitral Universitario Pr Edgar Santos
🇧🇷Salvador da Bahia, Brazil
Hôpital Saint-Louis
🇫🇷Paris, France
CHI Villeneuve Saint Georges
🇫🇷Villeneuve Saint Georges, France
Hospital Genral de Nova Iguaçu
🇧🇷Nova Iguaçu, Brazil
Hospital Nossa Senhora da Coceiçao
🇧🇷Porto alegre, Brazil
Hospital Sanatorio Pertenon
🇧🇷Porto Alegre, Brazil
STD/AIDS department
🇧🇷Sao Paulo, Brazil
Hôpital Lariboisière
🇫🇷Paris, France