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

Phase 4

Completed

Interventions: Drug: EFV/FTC/TDF
Drug: EFV/FTC/TDF + Losartan
Drug: FTC/TDF + MK-0518
Drug: FTC/TDF+MK-0518+Losartan

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%.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue.	48 weeks

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients With Changes in the Levels of CRP 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 Changes in the Levels of IL-6 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 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+ (%)	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)