Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation Mediators, Cardiovascular Risk and Neurocognitive Disorders in HIV Infected Patients Previously Effectively Treated

Study Overview
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Brief Summary
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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%.

Official Title
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Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: EFV/FTC/TDF + Losartan
* Drug: EFV/FTC/TDF
* Drug: FTC/TDF + MK-0518
* Drug: FTC/TDF+MK-0518+Losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years. Patients with HIV infection in antiretroviral treatment with EFV / FTC / TDF with undetectable viral load (VL <37 copies) for at least 48 weeks. Nadir CD4 +> 250 cells/mm3. Patients, properly informed, give their written consent to participate in the study. Exclusion Criteria: Criteria for patients with AIDS. Patients with active opportunistic diseases. Patients coinfected with HCV. Patients without tonsillar tissue. Treatment with other drugs receptor antagonists or angiotensin II converting enzyme inhibitors, angiotensin II. Kidney failure.(Glomerular Filtration Rate (GFR < 60 mL/mn) Severe liver failure (PT> 60% ). Pregnant women Known hypersensitivity or contraindication to any study drug. determination of blood pressure (BP) <100/60 mmHg Hyponatremia with serum Na numbers <132 Meq / l History of chronic vomiting the last 6 months History of chronic diarrhea the last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EFV/FTC/TDF<br> | Drug: EFV/FTC/TDF<br>* 600/200/245 mg, od, oral<br>|
| Experimental: EFV/FTC/TDF + Losartan<br> | Drug: EFV/FTC/TDF + Losartan<br>* 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.<br>|
| Experimental: FTC/TDF + MK-0518<br> | Drug: FTC/TDF + MK-0518<br>* FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral<br>|
| Experimental: FTC/TDF+MK-0518+Losartan<br> | Drug: FTC/TDF+MK-0518+Losartan<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. |  | 48 weeks | 
| 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 Reduced Intima-media Complex in Carotid Ultrasound 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+ (%) | 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) | 0, 48 weeks |