The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1
- Registration Number
- NCT01451333
- Lead Sponsor
- Kirby Institute
- Brief Summary
Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Conflicting evidence regarding the CNS exposure of the antiretroviral drug used for the encore1 study, efavirenz (EFV) have been described in related studies. There were recent study of two small series assessment of EFV exposure in the cerebral spinal fluid (CSF); one group reported small detectable EFV concentrations, while another observed undetectable EFV exposure in the CSF. Also, in a larger reported series comprising of 80 subjects on EFV-containing antiretroviral therapy, a CSF to plasma concentration suggested that there is limited movement of EFV out of the CSF. In HIV-1 infected subjects at steady state, EFV plasma level parameters are dose proportional following 200mg, 400mg, and 600mg daily doses. The CNS exposure of EFV at different daily dosing has not been described.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.
- Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
- CNS opportunistic infections in the past 12 weeks of randomisation
- Bacterial or viral meningitis in the past 12 weeks of randomisation
- Head injury requiring medical assessment in the past 12 weeks of randomisation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Reduced dose Efavirenz arm Efavirenz Patient's on main study that was randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd). Normal Efavirenz dose arm Efavirenz Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
- Primary Outcome Measures
Name Time Method comparison of mean CSF concentration of EFV from both doses after week 24. 24 weeks measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.
- Secondary Outcome Measures
Name Time Method CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis 24 weeks The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.
The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments 24 weeks The relationship between CSF EFV exposure and other study parameters such as race and sex. 24 weeks The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL) 24 weeks CSF HIV RNA measurement after 12 - 24 weeks of study therapy 24 weeks Relationship between plasma HIV RNA and CSF HIV RNA 24 weeks CSF biomarker analysis after 12 - 24 weeks of study therapy 24 weeks comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration 24 weeks
Trial Locations
- Locations (5)
Khon Kaen University
🇹ðŸ‡Khon Kaen, Thailand
Medical Group Practice
🇩🇪Berlin, Germany
HIVNAT Research Collaboration
🇹ðŸ‡Patumwan, Bangkok, Thailand
Imperial College, St. Mary's Hospital
🇬🇧Clinical Trials Centre, Winston Churchil Wing, London, United Kingdom
Chelsea and Westminster Hospital
🇬🇧HIV/GUM laboratory 5th floor St. Stephen Centre, London, United Kingdom