HIV Infections, Tuberculosis
Conditions
Keywords
HIV, Tuberculosis, Pharmacokinetics, Raltegravir, France, Brazil, treatment naive
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.
Interventions
DRUGraltegravir
tenofovir 245 mg / lamivudine 300 mg / raltegravir 400 mg
DRUGefavirenz
tenofovir 245 mg / lamivudine 300 mg / efavirenz 600 mg
Sponsors
Gilead Sciences
Merck Sharp & Dohme LLC
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Evolution of CD4 cell counts from baseline to week 48 | 48 weeks |
| 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 |
| Frequency, type, time to grade 3 or 4 adverse event | Through out the trial |
| Rate of success of TB treatment | 48 weeks |
| Anti-TB resistance rate | 48 weeks |
| Evolution of raltegravir and efavirenz trough concentration | Through out the trial |
| Frequency, type and time to a new AIDS-defining event or death | Through out the trial |
Countries
Brazil, France
Outcome results
None listed