HIV-1 Infection
Conditions
Brief summary
This is a open controlled trial in which 48 HIV-1 patients successfully treated with EFV/FTC/TDF will be randomized to one of 4 groups in equal proportion between arms (1:1). The four arms are as follows: Arm I: EFV / FTC / TDF (n = 12) Arm II: EFV / FTC / TDF + LST (n = 12) Arm III: FTC / TDF + MK-0518 (n = 12) Arm IV: FTC / TDF + LST + MK-0518 (n = 12) The allocation will take place in two phases: Phase I: 24 patients 1:1 receiving EFV/FTC/TDF vs. EFV/FTC/TDF + Losartan If losartan arm shows benefits we will proceed to the second phase: Phase II: 24 patients 1:1 to receive FTC/TDF+ MK-0518 versus FTC/TDF + MK-0518 + losartan. Patients will be followed up during 12 months to determinate the proportion of patients with decreased collagen deposition in TL equal to or greater than 50%.
Interventions
DRUGEFV/FTC/TDF + Losartan
EFV/FTC/TDF --\> oral, 600/200/245 mg, od Losartan --\> initial dose 50 mg/24h, in patients with good tolerance, dose will be increased to 100 mg/24H in week 12.
DRUGEFV/FTC/TDF
600/200/245 mg, od, oral
DRUGFTC/TDF + MK-0518
FTC/TDF --\> 200/245 mg, oral MK-0518 --\> 400 mg, oral
DRUGFTC/TDF+MK-0518+Losartan
FTC/TDF --\> 200/245 mg, oral MK-0518 --\> 400 mg, oral Losartan --\> -\> initial dose 50 mg/24h, in patients with good tolerance, dose will be increased to 100 mg/24n in week 12.
Sponsors
Felipe Garcia
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
1. Patients older than 18 years. 2. Patients with HIV infection in antiretroviral treatment with EFV / FTC / TDF with undetectable viral load (VL \<37 copies) for at least 48 weeks. 3. Nadir CD4 +\> 250 cells/mm3. 4. Patients, properly informed, give their written consent to participate in the study.
Exclusion criteria
1. Criteria for patients with AIDS. 2. Patients with active opportunistic diseases. 3. Patients coinfected with HCV. 4. Patients without tonsillar tissue. 5. Treatment with other drugs receptor antagonists or angiotensin II converting enzyme inhibitors, angiotensin II. 6. Kidney failure.(Glomerular Filtration Rate (GFR \< 60 mL/mn) 7. Severe liver failure (PT\> 60% ). 8. Pregnant women 9. Known hypersensitivity or contraindication to any study drug. 10. determination of blood pressure (BP) \<100/60 mmHg 11. Hyponatremia with serum Na numbers \<132 Meq / l 12. History of chronic vomiting the last 6 months 13. History of chronic diarrhea the last 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. | 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Changes in the Levels of CRP in Different Groups. | 48 weeks | — |
| Proportion of Patients With Changes in the Levels of D-dimer in Different Groups. | 48 weeks | — |
| Proportion of Patients With Increased CD4 in Peripheral Blood. | 48 weeks | — |
| Proportion of Patients With Increased CD4 in Lymphatic Tissue. | week 48 | — |
| Proportion of Patients With Undetectable Plasma Viral Load in Different Groups | 48 weeks | — |
| Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups | week 48 | — |
| Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups. | 48 weeks | — |
| Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. | 48 weeks | — |
| Proportion of Patients With Changes in Levels of Metalloproteinases | 48 weeks | — |
| Proportion of Patients With Changes in Levels of beta2-microglobulin. | 48 weeks | — |
| Proportion of Patients With Changes in Levels of CSF Cells. | 48 weeks | — |
| Proportion of Patients With Changes in Levels of Proteins. | 48 weeks | — |
| Proportion of Patients With Improvement in Neuropsychological Test | 48 weeks | — |
| Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups. | up to 48 weeks | — |
| Changes in CD4 CD38+ HLADR+ (%) | 0, 48 weeks | Marker of activation in CD4 T cells. This Outcome Measure is reporting a change in the percentage of CD4 CD38+ HLADR+ T cells at 48 months minus the percentage at 0 weeks (baseline) |
| Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups. | 48 weeks | — |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EFV/FTC/TDF EFV/FTC/TDF: 600/200/245 mg, od, oral | 12 |
| EFV/FTC/TDF + Losartan EFV/FTC/TDF + Losartan: EFV/FTC/TDF --\> oral, 600/200/245 mg, od Losartan --\> initial dose 50 mg/24h, in patients with good tolerance, dose will be increased to 100 mg/24H in week 12. | 10 |
| FTC/TDF + MK-0518 FTC/TDF + MK-0518: FTC/TDF --\> 200/245 mg, oral MK-0518 --\> 400 mg, oral | 10 |
| FTC/TDF+MK-0518+Losartan FTC/TDF+MK-0518+Losartan: FTC/TDF --\> 200/245 mg, oral MK-0518 --\> 400 mg, oral Losartan --\> -\> initial dose 50 mg/24h, in patients with good tolerance, dose will be increased to 100 mg/24n in week 12. | 10 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | EFV/FTC/TDF + Losartan | FTC/TDF + MK-0518 | EFV/FTC/TDF | FTC/TDF+MK-0518+Losartan | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 12 Participants | 10 Participants | 42 Participants |
| Age, Continuous | 43 years | 43 years | 40 years | 35 years | 41 years |
| Region of Enrollment Spain | 10 participants | 10 participants | 12 participants | 10 participants | 42 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 11 Participants | 10 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 6 / 12 | 6 / 10 | 3 / 10 | 6 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue.
Time frame: 48 weeks
Population: Eligibility criteria were being older than 18 years, being on ART with a combined triple therapy regimen and having viral load under the limit of detection for at least the previous 48 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Changes in CD4 CD38+ HLADR+ (%)
Marker of activation in CD4 T cells. This Outcome Measure is reporting a change in the percentage of CD4 CD38+ HLADR+ T cells at 48 months minus the percentage at 0 weeks (baseline)
Time frame: 0, 48 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EFV/FTC/TDF | Changes in CD4 CD38+ HLADR+ (%) | 2.3 percentage of CD4 T cells |
| EFV/FTC/TDF + Losartan | Changes in CD4 CD38+ HLADR+ (%) | 4 percentage of CD4 T cells |
| FTC/TDF + MK-0518 | Changes in CD4 CD38+ HLADR+ (%) | 1.8 percentage of CD4 T cells |
| FTC/TDF+MK-0518+Losartan | Changes in CD4 CD38+ HLADR+ (%) | 2.2 percentage of CD4 T cells |
p-value: 0.02Kruskal-Wallis
Secondary
Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups.
Time frame: 48 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EFV/FTC/TDF | Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups. | -0.03 ratio |
| EFV/FTC/TDF + Losartan | Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups. | 0.04 ratio |
| FTC/TDF + MK-0518 | Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups. | 0.36 ratio |
| FTC/TDF+MK-0518+Losartan | Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups. | 0.37 ratio |
p-value: 0.01Kruskal-Wallis
Secondary
Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups.
Time frame: up to 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups. | 6 participants |
| EFV/FTC/TDF + Losartan | Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups. | 6 participants |
| FTC/TDF + MK-0518 | Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups. | 3 participants |
| FTC/TDF+MK-0518+Losartan | Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups. | 6 participants |
p-value: 0.49Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in Levels of beta2-microglobulin.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in Levels of beta2-microglobulin. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in Levels of beta2-microglobulin. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in Levels of beta2-microglobulin. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in Levels of beta2-microglobulin. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in Levels of CSF Cells.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in Levels of CSF Cells. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in Levels of CSF Cells. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in Levels of CSF Cells. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in Levels of CSF Cells. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in Levels of Metalloproteinases
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in Levels of Metalloproteinases | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in Levels of Metalloproteinases | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in Levels of Metalloproteinases | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in Levels of Metalloproteinases | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in Levels of Proteins.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in Levels of Proteins. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in Levels of Proteins. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in Levels of Proteins. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in Levels of Proteins. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in the Levels of CRP in Different Groups.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in the Levels of CRP in Different Groups. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in the Levels of CRP in Different Groups. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in the Levels of CRP in Different Groups. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in the Levels of CRP in Different Groups. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in the Levels of D-dimer in Different Groups.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in the Levels of D-dimer in Different Groups. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in the Levels of D-dimer in Different Groups. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in the Levels of D-dimer in Different Groups. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in the Levels of D-dimer in Different Groups. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Changes in the Levels of IL-6 in Different Groups.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Improvement in Neuropsychological Test
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Improvement in Neuropsychological Test | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Improvement in Neuropsychological Test | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Improvement in Neuropsychological Test | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Improvement in Neuropsychological Test | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Increased CD4 in Lymphatic Tissue.
Time frame: week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Increased CD4 in Lymphatic Tissue. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Increased CD4 in Lymphatic Tissue. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Increased CD4 in Lymphatic Tissue. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Increased CD4 in Lymphatic Tissue. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Increased CD4 in Peripheral Blood.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Increased CD4 in Peripheral Blood. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Increased CD4 in Peripheral Blood. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Increased CD4 in Peripheral Blood. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Increased CD4 in Peripheral Blood. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups.
Time frame: 48 weeks
Population: Carotid ultrasound was performed at baseline in 41 out the 42 patients. However, only 36 patients repeated the ultrasound at week 48, and were included in the analysis (9 in each randomised group).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups. | 0 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups. | 0 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups. | 0 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups. | 0 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Undetectable Plasma Viral Load in Different Groups
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Undetectable Plasma Viral Load in Different Groups | 12 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Undetectable Plasma Viral Load in Different Groups | 10 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Undetectable Plasma Viral Load in Different Groups | 10 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Undetectable Plasma Viral Load in Different Groups | 10 participants |
p-value: 1Chi-squared, Corrected
Secondary
Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups
Time frame: week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV/FTC/TDF | Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups | 12 participants |
| EFV/FTC/TDF + Losartan | Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups | 10 participants |
| FTC/TDF + MK-0518 | Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups | 10 participants |
| FTC/TDF+MK-0518+Losartan | Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups | 10 participants |
p-value: 1Chi-squared, Corrected