HIV
Conditions
Brief summary
The main objective is to determine the feasibility of maintaining virologic suppression on standard plasma viral load by dose reduction of ATRIPLA ®.
Detailed description
The main objective of this study is to determine the feasibility of maintaining virologic suppression on standard plasma viral load (limit of detection 37 copies / mL) of a dose reduction strategy of ATRIPLA ® once a day to three tablets per week in patients infected with HIV-1 with sustained suppression of plasma viral load standard for more than two years.
Interventions
DRUGATRIPLA
Sponsors
Anna Cruceta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (≥ 18 years) * HIV-1 infection, clinical stability, and treatment with ATRIPLA ® for the past two years. * Standard plasma viral load below the limit of detection for at least 2 years. * CD4 count above 350/mm3 at the time of the consideration for the study. * Negative pregnancy test in women of childbearing age, and commitment acceptable contraceptive use for at least 2 weeks before day 1 and until at least 6 months after the last dose of study drug. * Patients should be given written informed consent * In the opinion of the investigator, be able to follow the design of the protocol visits
Exclusion criteria
* Patients who have experienced virologic failure prior to any antiretroviral regimen * Evidence of previous mutations versus efavirenz, tenofovir and emtricitabine * Use of any other chronic treatment plus ATRIPLA has been introduced in the 6 months prior to entry of the patient in the study * Any contraindication to study drug * Any condition not ensure proper adherence to the study at the discretion of the attending physician of the patient * Uncontrolled preexisting psychiatric illness * Any current sign of alcoholism or other drug use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Free of Treatment Failure (Noncompleter = Failure) at 24 Weeks. | 24 weeks | Treatment failure defined as any of the following possibilities occurring within the 24-week study framework: virological failure (confirmed plasma viral load 37 copies/ml), discontinuation of the antiretroviral therapy schedule irrespective of the reason, consent withdrawal, lost to follow-up, pregnancy, inability to comply with the study or any other reason that could make the doctor in charge consider the cessation of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline to 24 Weeks in the Viral Reservoir in Peripheral Blood Mononuclear Cells | baseline and 6 months | — |
| Immunological | baseline and 6 months | Changes from baseline to 24 weeks in the production of TRECs, the immunological profile of activation (CD38 and HLA-DR) and senescence (CD57 and CD28) in CD4 and CD8 lineages in the proportions of naive T cells effector and memory (CCR7 and CD45RA), and changes in the levels of apoptosis in vitro by staining with annexin V. |
| Changes in Plasma Levels of Efavirenz. | baseline and 6 months | — |
| Changes in Sleep Quality (Pittsburgh Sleep Quality Index). | baseline and 6 months | — |
| The Proportion of Patients With Ultrasensitive Viral Load (<1 Copy / mL) After 24 Weeks. | 24 weeks | — |
| Changes in Plasma Levels of Vitamin D. | baseline and 6 months | — |
| Changes in Lipid Profile. | baseline and 6 months | — |
| Changes in Estimated Glomerular Filtration Rate. | baseline and 6 months | — |
| General Safety (Report Adverse Events, Serious Adverse Events and Treatment Discontinuation Due to Adverse Events) | 24 weeks | — |
Countries
Spain
Participant flow
Recruitment details
Participants were recruited between 3 June 2013 and 30 May 2014 at Hospital Clínic of Barcelona.
Pre-assignment details
68 patients were assessed for eligibility, 61 underwent randomization and received at least one dose of study drugs. Seven patients were excluded because of refusal to participate (lack of time, n¼4; lack of interest, n¼1; fear of viral failure, n¼1) or evidence of illicit drug consumption (n¼1).
Participants by arm
| Arm | Count |
|---|---|
| ATRIPLA Three Days a Week (3W) Atripla (600 mg/200 mg/245 mg) three days a week (Mondays, Wednesdays and Fridays). | 30 |
| ATRIPLA One Time a Day (OD) Atripla (600 mg/200 mg/245 mg) one time a day. | 31 |
| Total | 61 |
Baseline characteristics
| Characteristic | ATRIPLA Three Days a Week (3W) | ATRIPLA One Time a Day (OD) | Total |
|---|---|---|---|
| Age, Continuous | 47.8 years | 48.5 years | 48.2 years |
| Race/Ethnicity, Customized Ethnicity Caucasian | 19 Participants | 21 Participants | 40 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 27 Participants | 27 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 13 / 30 | 11 / 31 |
| serious Total, serious adverse events | 0 / 30 | 0 / 31 |
Outcome results
Primary
Proportion of Patients Free of Treatment Failure (Noncompleter = Failure) at 24 Weeks.
Treatment failure defined as any of the following possibilities occurring within the 24-week study framework: virological failure (confirmed plasma viral load 37 copies/ml), discontinuation of the antiretroviral therapy schedule irrespective of the reason, consent withdrawal, lost to follow-up, pregnancy, inability to comply with the study or any other reason that could make the doctor in charge consider the cessation of the study.
Time frame: 24 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATRIPLA Three Days a Week (3W) | Proportion of Patients Free of Treatment Failure (Noncompleter = Failure) at 24 Weeks. | Patients free of treatment failure | 30 Participants |
| ATRIPLA Three Days a Week (3W) | Proportion of Patients Free of Treatment Failure (Noncompleter = Failure) at 24 Weeks. | Patients with treatment failure | 0 Participants |
| ATRIPLA One Time a Day (OD) | Proportion of Patients Free of Treatment Failure (Noncompleter = Failure) at 24 Weeks. | Patients free of treatment failure | 31 Participants |
| ATRIPLA One Time a Day (OD) | Proportion of Patients Free of Treatment Failure (Noncompleter = Failure) at 24 Weeks. | Patients with treatment failure | 0 Participants |
Secondary
Changes in Estimated Glomerular Filtration Rate.
Time frame: baseline and 6 months
Secondary
Changes in Lipid Profile.
Time frame: baseline and 6 months
Secondary
Changes in Plasma Levels of Efavirenz.
Time frame: baseline and 6 months
Secondary
Changes in Plasma Levels of Vitamin D.
Time frame: baseline and 6 months
Secondary
Changes in Sleep Quality (Pittsburgh Sleep Quality Index).
Time frame: baseline and 6 months
Secondary
General Safety (Report Adverse Events, Serious Adverse Events and Treatment Discontinuation Due to Adverse Events)
Time frame: 24 weeks
Secondary
Immunological
Changes from baseline to 24 weeks in the production of TRECs, the immunological profile of activation (CD38 and HLA-DR) and senescence (CD57 and CD28) in CD4 and CD8 lineages in the proportions of naive T cells effector and memory (CCR7 and CD45RA), and changes in the levels of apoptosis in vitro by staining with annexin V.
Time frame: baseline and 6 months
Secondary
The Change From Baseline to 24 Weeks in the Viral Reservoir in Peripheral Blood Mononuclear Cells
Time frame: baseline and 6 months
Secondary
The Proportion of Patients With Ultrasensitive Viral Load (<1 Copy / mL) After 24 Weeks.
Time frame: 24 weeks