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

This study has been completed.
Sponsor:
Collaborator:
The Campbell Foundation
Information provided by (Responsible Party):
Cal Cohen, Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT00414635
First received: December 20, 2006
Last updated: February 9, 2012
Last verified: February 2012
Results First Received: July 22, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: efavirenz
Drug: tenofovir
Drug: emtricitabine

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment took place between August 21, 2006 and November 9, 2007. Recruitment occured at multiple site locations (research clinics and private practice).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Participant Flow:   Overall Study
    FOTO     Control  
STARTED     30     30  
COMPLETED     25     28  
NOT COMPLETED     5     2  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.
Total Total of all reporting groups

Baseline Measures
    FOTO     Control     Total  
Number of Participants  
[units: participants]
  30     30     60  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     30     28     58  
>=65 years     0     2     2  
Age  
[units: years]
Mean ± Standard Deviation
  42  ± 8.1     47  ± 9.9     44  ± 9.4  
Gender  
[units: participants]
     
Female     5     5     10  
Male     25     25     50  
Region of Enrollment  
[units: participants]
     
United States     30     30     60  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml)   [ Time Frame: 24 weeks ]

Measure Type Primary
Measure Title Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml)
Measure Description Percentage of Participants maintaining full Virologic Suppression (less than 50 RNA cps/ml)
Time Frame 24 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     28  
Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml)  
[units: Percentage of Participants]
  100     86  

No statistical analysis provided for Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml)



2.  Secondary:   Mean CD4+ T-cell Count Increases From Baseline to Week 24.   [ Time Frame: Baseline to Week 24 ]

Measure Type Secondary
Measure Title Mean CD4+ T-cell Count Increases From Baseline to Week 24.
Measure Description No text entered.
Time Frame Baseline to Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     28  
Mean CD4+ T-cell Count Increases From Baseline to Week 24.  
[units: cells/ml]
Mean ( 95% Confidence Interval )
  -1.9  
  ( -50.6 to 46.9 )  
  -9.3  
  ( -57.9 to 39.3 )  

No statistical analysis provided for Mean CD4+ T-cell Count Increases From Baseline to Week 24.



3.  Secondary:   Quality of Life   [ Time Frame: 4 weeks ]

Measure Type Secondary
Measure Title Quality of Life
Measure Description 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.
Time Frame 4 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The questionnaire was only applicable to FOTO arm

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     0  
Quality of Life  
[units: Units on a Scale]
Median ( Inter-Quartile Range )
  9.5  
  ( 8 to 10 )  
   
   

No statistical analysis provided for Quality of Life



4.  Secondary:   Absolute Number of Virological "Blip" Events Occurring Over 24 Weeks   [ Time Frame: Baseline to week 24 ]

Measure Type Secondary
Measure Title Absolute Number of Virological "Blip" Events Occurring Over 24 Weeks
Measure Description Total number of "blip" events in each arm. Blips are defined as HIV RNA > 50 and < 200 cps/ml
Time Frame Baseline to week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     28  
Absolute Number of Virological "Blip" Events Occurring Over 24 Weeks  
[units: blip events]
  8     10  

No statistical analysis provided for Absolute Number of Virological "Blip" Events Occurring Over 24 Weeks



5.  Secondary:   Trough Blood Levels of Efavirenz in Both Arms   [ Time Frame: 12 or 60 hours ]

Measure Type Secondary
Measure Title Trough Blood Levels of Efavirenz in Both Arms
Measure Description blood levels of efavirenz measured at 60 hours post last dose in FOTO arm and 12 hours post last dose in daily arm (control)
Time Frame 12 or 60 hours  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     28  
Trough Blood Levels of Efavirenz in Both Arms  
[units: Percentage of Participants]
   
>1000 nanograms/milliliter (ng/ml)     48     90  
500-999 nanograms/milliliter (ng/ml)     37     1  
<500 nanograms/milliliter (ng/ml)     15     9  

No statistical analysis provided for Trough Blood Levels of Efavirenz in Both Arms



6.  Secondary:   Self-reported Adherence Summary in Both Arms   [ Time Frame: 4, 12 and 24 weeks ]

Measure Type Secondary
Measure Title Self-reported Adherence Summary in Both Arms
Measure Description Percentage of participants who missed one or more doses in weekly regimen.
Time Frame 4, 12 and 24 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     28  
Self-reported Adherence Summary in Both Arms  
[units: percentage of participants]
   
Week 4     10     17  
Week 12     15     7  
Week 24     8     11  

No statistical analysis provided for Self-reported Adherence Summary in Both Arms



7.  Secondary:   Deviation From FOTO Schedule by One Extra Dose   [ Time Frame: 4, 12, 24 weeks ]

Measure Type Secondary
Measure Title Deviation From FOTO Schedule by One Extra Dose
Measure Description Percentage of FOTO participants who took a dose during weekend planned interuption period
Time Frame 4, 12, 24 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FOTO Participants changing to 5 days on, 2 days off (FOTO). The 5/2 intermittent treatment arm will take their antiretrovirals for 5 consecutive days followed by 2 days off for 48 weeks (provided their HIV RNA remains undetectable on an ultrasensitive assay).
Control Daily regimen (7 days)• The control arm will take their antiretrovirals for 7 days a week for the first 24 weeks and then cross over to the 5/2 intermittent treatment schedule (if their HIV RNA remains undetectable on an ultrasensitive assay) for the remainder of the study.

Measured Values
    FOTO     Control  
Number of Participants Analyzed  
[units: participants]
  25     0  
Deviation From FOTO Schedule by One Extra Dose  
[units: Percentage of Participants]
   
Week 4     10      
Week 12     4      
Week 24     8      

No statistical analysis provided for Deviation From FOTO Schedule by One Extra Dose




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Conclusions are limited by the small "n" studied. The results are only applicable to the specific drug regimen studied and thus can not be generalized to all ART. We only studied individuals already virologically undetectable.


  More Information