FOTO: Five Consecutive Days on Treatment With Efavirenz, Tenofovir, and Emtricitabine Followed by Two Days Off Treatment Versus Continuous Treatment

Study Overview
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Brief Summary
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For people with HIV who are currently taking specific medications (including Sustiva (efavirenz)) and have no detectable viral load, this study tracks how patients do if they take their medications for five days of the week compared with seven days of the week.

Detailed Description
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The purpose of this study is to evaluate virologic control of a weekly schedule of 5 days of treatment followed by two days off treatment versus continuous treatment with the same regimen. This is a larger study based on the results of our successful pilot study using the same protocol. The 48 week, phase IV trial addresses the issues of the high cost of HIV treatment, adherence problems associated with daily treatment, and cumulative toxicities. Virologic and immunologic parameters, drug levels of efavirenz, adherence, and toxicity will be measured. Subjects will have to be seen at CRI for 6 visits after randomization. Subjects randomized to daily therapy will cross over to 5/2 therapy at 24 weeks if their viral load remains undetectable.

Official Title
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A Randomized Controlled Trial of a Weekly Schedule of Five Consecutive Days on Treatment With Efavirenz, Tenofovir, and Emtricitabine Followed by Two Days Off Treatment (5/2 Intermittent Treatment Schedule) Versus Continuous Treatment in Individuals With Virologic Suppression on This Combination

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Intermitent Dosing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older CD4 count > or = 200 Viral load < 50 Treatment with a regimen containing efavirenz and tenofovir and lamivudine or emtricitabine for at least 90 days prior to screening Exclusion Criteria: Detectable HIV RNA on an ultrasensitive assay within the 90 days preceding screening Prior evidence of intermediate or high level resistance to efavirenz, tenofovir or cytidine analogues Hepatitis B infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study is designed to compare the control and the experimental arm groups for 24 weeks of treatment. After 24 weeks, subjects on the control arm then cross over to the experimental intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control Arm with Week 24 Crossover<br>Subjects randomized to the control arm will remain on daily dosing of the pre-study regimen of 600mg efavirenz and 1 coformulated tablet of 300mg tenofovir df + 200 mg emtricitabine by mouth daily, or the equivalent coformulated single tablet of 600mg efavirenz + 300mg tenofovir df + 200 mg emtricitabine by mouth daily for 24 weeks. After 24 weeks of daily therapy subjects on this arm may be eligible to cross over to the experimental arm regimen of the coformulated single tablet of 600 mg efavirenz +300 mg tenofovir df +200 mg of emtricitabine on the 5/2 intermittent dosing treatment schedule for the remainder of the study. | Drug: Intermitent Dosing<br>* Intermittent dosing treatment is the maintenance of the 5/2 schedule, where the regimen, 300 mg tenofovir td, 600 mg efavirenz, 200 mg emtricitabine is dosed for 5 consecutive days - typically Monday through Friday - followed by two days off of medication, 300 mg tenofovir td, 600 mg efavirenz, 200 mg emtricitabine. .<br>|
| Experimental: 5/2 Intermitent Treatment Arm<br>Subjects randomized to the 5/2 intermittent dosing treatment schedule regimen will be prescribed the pre-study regimen of 600mg efavirenz and 1 coformulated tablet of 300mg tenofovir df + 200 mg emtricitabine by mouth daily, or the equivalent coformulated single tablet of 600mg efavirenz + 300mg tenofovir df + 200 mg emtricitabine by mouth daily, for 5 consecutive days per week followed by 2 days off of these medications, 600 mg efavirenz, 300 mg tenoforvir dt and 200 mg emtricitabine, for 48 weeks. | Drug: Intermitent Dosing<br>* Intermittent dosing treatment is the maintenance of the 5/2 schedule, where the regimen, 300 mg tenofovir td, 600 mg efavirenz, 200 mg emtricitabine is dosed for 5 consecutive days - typically Monday through Friday - followed by two days off of medication, 300 mg tenofovir td, 600 mg efavirenz, 200 mg emtricitabine. .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml) | Percentage of Participants maintaining full Virologic Suppression (less than 50 RNA cps/ml) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean CD4+ T-cell Count Increases From Baseline to Week 24. |  | Baseline to Week 24 | 
| Quality of Life | Participant preference of antiretroviral (ART) regimen determined on a scale ranging from 0 to 10. O was defined as I Perfer taking HIV medications 7 days/week and 10 was defined as I perfer 5 days on and 2 days off. We present results of a single question on quality of life experienced while on their study ART regimen. | 4 weeks | 
| Absolute Number of Virological Blip Events Occurring Over 24 Weeks | Total number of blip events in each arm. Blips are defined as HIV RNA > 50 and < 200 cps/ml | Baseline to week 24 | 
| Trough Blood Levels of Efavirenz in Both Arms | blood levels of efavirenz measured at 60 hours post last dose in FOTO arm and 12 hours post last dose in daily arm (control) | 12 or 60 hours | 
| Self-reported Adherence Summary in Both Arms | Percentage of participants who missed one or more doses in weekly regimen. | 4, 12 and 24 weeks | 
| Deviation From FOTO Schedule by One Extra Dose | Percentage of FOTO participants who took a dose during weekend planned interuption period | 4, 12, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FOTO, HIV/AIDS, efavirenz, tenofovir, emtricitabine, treatment interruption, Atripla, Truvada, Treatment Experienced