The Neurocognitive Sub-study of Encore1

Study Overview
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Brief Summary
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The purpose is to investigate whether HIV and HIV medication can affect certain areas of brain function. This study will look at possible changes in brain function including memory, concentration and thought processes to see if there are any differences between the two doses of efavirenz used in the Encore1 study and also the level of efavirenz in the blood

Official Title
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The Neurocognitive Sub Study of Encore1:A Randomised, Double-Blind, Placebo-Controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus 2N(t)RTI in Antiretroviral-naïve HIV-Infected Individuals Over 96 Weeks A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks

Conditions
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HIV

Intervention / Treatment
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* Drug: Efavirenz
* Drug: Efavirenz


Participation Criteria
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Eligibility Criteria
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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 brain disease Recent (<6months ) head injury Current major depression or psychosis Current alcohol abuse Intended use of recreational drugs during study period Uncontrolled medical conditions deemed to potentially interfere with cognitive function (e.g. uncontrolled diabetes, pyrexial illness, uraemia etc)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced dose Efavirenz arm<br>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). | Drug: Efavirenz<br>* 400mg qd; 2 x 200mg<br>|
| Active Comparator: Normal Efavirenz dose arm<br>Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd) | Drug: Efavirenz<br>* 600mg qd; 3 x 200mg qd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the comparison between of neurocognitive function in patients initiating sdEFV and 400EFV |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The association between week 4 plasma EFV levels and change from baseline neurocognitive function to week 4 and 24. |  | Week 24 | 
| To assess dynamic changes in neurocognitive function over the total duration of follow-up. |  | 96 weeks |