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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Intermitent Dosing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20009
      • Whitman-Walker Clinic
    • Washington, D.C., District of Columbia, United States, 20037
      • CARE-ID
  • Florida
    • Miami, Florida, United States, 33133
      • Steinhart Medical Associates
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Vero Beach, Florida, United States, 32960
      • Treasure Chest Infectious Disease
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative of New England - Boston
    • Springfield, Massachusetts, United States, 01107
      • Community Research Initiative of New England - West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control Arm with Week 24 Crossover; 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; 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. .
Experimental: 5/2 Intermitent Treatment Arm; 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; 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. .

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Community Research Initiative of New England
• Collaborators: The Campbell Foundation
• Investigators: Principal Investigator: Calvin J Cohen, MD, MSc, CRI

Publications and helpful links

Helpful Links

• Web page of CRI, the nonprofit research group sponsoring the study

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 20, 2006
• First Submitted That Met QC Criteria: December 20, 2006
• First Posted (Estimate): December 21, 2006

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: August 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: tenofovir; Treatment Experienced; Truvada; HIV/AIDS; efavirenz; emtricitabine; treatment interruption; Atripla; FOTO
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 06-156