HIV Infections
Conditions
Keywords
HIV/AIDS, efavirenz, tenofovir, emtricitabine, FOTO, treatment interruption, Atripla, Truvada, Treatment Experienced
Brief summary
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
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.
Interventions
DRUGIntermitent 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. .
Sponsors
The Campbell Foundation
Community Research Initiative of New England
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml) | 24 weeks | Percentage of Participants maintaining full Virologic Suppression (less than 50 RNA cps/ml) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | 4 weeks | 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. |
| Absolute Number of Virological Blip Events Occurring Over 24 Weeks | Baseline to week 24 | Total number of blip events in each arm. Blips are defined as HIV RNA \> 50 and \< 200 cps/ml |
| Mean CD4+ T-cell Count Increases From Baseline to Week 24. | Baseline to Week 24 | — |
| Self-reported Adherence Summary in Both Arms | 4, 12 and 24 weeks | Percentage of participants who missed one or more doses in weekly regimen. |
| Deviation From FOTO Schedule by One Extra Dose | 4, 12, 24 weeks | Percentage of FOTO participants who took a dose during weekend planned interuption period |
| Trough Blood Levels of Efavirenz in Both Arms | 12 or 60 hours | blood levels of efavirenz measured at 60 hours post last dose in FOTO arm and 12 hours post last dose in daily arm (control) |
Countries
United States
Participant flow
Recruitment details
Recruitment took place between August 21, 2006 and November 9, 2007. Recruitment occured at multiple site locations (research clinics and private practice).
Participants by arm
| Arm | Count |
|---|---|
| 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). | 30 |
| 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. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Control | FOTO | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 30 Participants | 58 Participants |
| Age, Continuous | 47 years STANDARD_DEVIATION 9.9 | 42 years STANDARD_DEVIATION 8.1 | 44 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 30 | 9 / 30 |
| serious Total, serious adverse events | 0 / 30 | 2 / 30 |
Outcome results
Primary
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)
Time frame: 24 weeks
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOTO | Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml) | 100 Percentage of Participants |
| Control | Percentage of Participants Who Maintained Virologic Suppression (Less Than 50 RNA Cps/ml) | 86 Percentage of Participants |
Secondary
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
Time frame: Baseline to week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOTO | Absolute Number of Virological Blip Events Occurring Over 24 Weeks | 8 blip events |
| Control | Absolute Number of Virological Blip Events Occurring Over 24 Weeks | 10 blip events |
Secondary
Deviation From FOTO Schedule by One Extra Dose
Percentage of FOTO participants who took a dose during weekend planned interuption period
Time frame: 4, 12, 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOTO | Deviation From FOTO Schedule by One Extra Dose | Week 24 | 8 Percentage of Participants |
| FOTO | Deviation From FOTO Schedule by One Extra Dose | Week 4 | 10 Percentage of Participants |
| FOTO | Deviation From FOTO Schedule by One Extra Dose | Week 12 | 4 Percentage of Participants |
Secondary
Mean CD4+ T-cell Count Increases From Baseline to Week 24.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FOTO | Mean CD4+ T-cell Count Increases From Baseline to Week 24. | -1.9 cells/ml |
| Control | Mean CD4+ T-cell Count Increases From Baseline to Week 24. | -9.3 cells/ml |
Secondary
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.
Time frame: 4 weeks
Population: The questionnaire was only applicable to FOTO arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOTO | Quality of Life | 9.5 Units on a Scale |
Secondary
Self-reported Adherence Summary in Both Arms
Percentage of participants who missed one or more doses in weekly regimen.
Time frame: 4, 12 and 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOTO | Self-reported Adherence Summary in Both Arms | Week 4 | 10 percentage of participants |
| FOTO | Self-reported Adherence Summary in Both Arms | Week 24 | 8 percentage of participants |
| FOTO | Self-reported Adherence Summary in Both Arms | Week 12 | 15 percentage of participants |
| Control | Self-reported Adherence Summary in Both Arms | Week 24 | 11 percentage of participants |
| Control | Self-reported Adherence Summary in Both Arms | Week 4 | 17 percentage of participants |
| Control | Self-reported Adherence Summary in Both Arms | Week 12 | 7 percentage of participants |
Secondary
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)
Time frame: 12 or 60 hours
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOTO | Trough Blood Levels of Efavirenz in Both Arms | >1000 nanograms/milliliter (ng/ml) | 48 Percentage of Participants |
| FOTO | Trough Blood Levels of Efavirenz in Both Arms | 500-999 nanograms/milliliter (ng/ml) | 37 Percentage of Participants |
| FOTO | Trough Blood Levels of Efavirenz in Both Arms | <500 nanograms/milliliter (ng/ml) | 15 Percentage of Participants |
| Control | Trough Blood Levels of Efavirenz in Both Arms | >1000 nanograms/milliliter (ng/ml) | 90 Percentage of Participants |
| Control | Trough Blood Levels of Efavirenz in Both Arms | 500-999 nanograms/milliliter (ng/ml) | 1 Percentage of Participants |
| Control | Trough Blood Levels of Efavirenz in Both Arms | <500 nanograms/milliliter (ng/ml) | 9 Percentage of Participants |