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.

Inclusion Criteria:

• All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.

Exclusion Criteria:

• 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