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

Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation

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%.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: EFV/FTC/TDF; Drug: EFV/FTC/TDF + Losartan; Drug: FTC/TDF + MK-0518; Drug: FTC/TDF+MK-0518+Losartan

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Felipe Garcia

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: February 8, 2012
• First Submitted That Met QC Criteria: February 8, 2012
• First Posted (Estimate): February 9, 2012

Study Record Updates

• Last Update Posted (Actual): August 2, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Raltegravir Potassium; Losartan
• Other Study ID Numbers: HIV-IMMUNESARTAN; 2011-002071-42 (EudraCT Number)