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

• Sponsor: Felipe Garcia (Other)
• Overall Status: Completed
• CT.gov ID: NCT01529749
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 4
• Duration (Months): 48
• Patients Per Site Per Month: 1

Study Details

Study Description

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%.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: EFV/FTC/TDF + Losartan; Drug: EFV/FTC/TDF; Drug: FTC/TDF + MK-0518; Drug: FTC/TDF+MK-0518+Losartan	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue. [48 weeks]

Secondary Outcome Measures

1. Proportion of Patients With Changes in the Levels of IL-6 in Different Groups. [48 weeks]

2. Proportion of Patients With Changes in the Levels of CRP in Different Groups. [48 weeks]

3. Proportion of Patients With Changes in the Levels of D-dimer in Different Groups. [48 weeks]

4. Proportion of Patients With Increased CD4 in Peripheral Blood. [48 weeks]

5. Proportion of Patients With Increased CD4 in Lymphatic Tissue. [week 48]

6. Proportion of Patients With Undetectable Plasma Viral Load in Different Groups [48 weeks]

7. Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups [week 48]

8. Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups. [48 weeks]

9. Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups. [48 weeks]

10. Proportion of Patients With Changes in Levels of Metalloproteinases [48 weeks]

11. Proportion of Patients With Changes in Levels of beta2-microglobulin. [48 weeks]

12. Proportion of Patients With Changes in Levels of CSF Cells. [48 weeks]

13. Proportion of Patients With Changes in Levels of Proteins. [48 weeks]

14. Proportion of Patients With Improvement in Neuropsychological Test [48 weeks]

15. Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups. [up to 48 weeks]

16. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clinic	Barcelona		Spain	08036

Sponsors and Collaborators

• Felipe Garcia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Felipe Garcia, Dr, Hospital Clinic of Barcelona
• ClinicalTrials.gov Identifier: NCT01529749
• Other Study ID Numbers: HIV-IMMUNESARTAN; 2011-002071-42
• First Posted: Feb 9, 2012
• Last Update Posted: Aug 2, 2019
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Inflammation; Raltegravir Potassium; Losartan

Study Results

Participant Flow

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Period Title: Overall Study
STARTED	12	12	12	12
COMPLETED	12	10	10	10
NOT COMPLETED	0	2	2	2

Baseline Characteristics

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan	Total
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.	Total of all reporting groups
Overall Participants	12	10	10	10	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	10 100%	10 100%	10 100%	42 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	40	43	43	35	41
Sex: Female, Male (Count of Participants)
Female	1 8.3%	2 20%	0 0%	0 0%	3 7.1%
Male	11 91.7%	8 80%	10 100%	10 100%	39 92.9%
Region of Enrollment (participants) [Number]
Spain	12 100%	10 100%	10 100%	10 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

2. Secondary Outcome

Title	Proportion of Patients With Changes in the Levels of IL-6 in Different Groups.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

3. Secondary Outcome

Title	Proportion of Patients With Changes in the Levels of CRP in Different Groups.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

4. Secondary Outcome

Title	Proportion of Patients With Changes in the Levels of D-dimer in Different Groups.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

5. Secondary Outcome

Title	Proportion of Patients With Increased CD4 in Peripheral Blood.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

6. Secondary Outcome

Title	Proportion of Patients With Increased CD4 in Lymphatic Tissue.
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

7. Secondary Outcome

Title	Proportion of Patients With Undetectable Plasma Viral Load in Different Groups
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	12 100%	10 100%	10 100%	10 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

8. Secondary Outcome

Title	Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	12 100%	10 100%	10 100%	10 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

9. Secondary Outcome

Title	Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Median (Inter-Quartile Range) [ratio]	-0.03	0.04	0.36	0.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Kruskal-Wallis
	Comments

10. Secondary Outcome

Title	Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	9	9	9	9
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

11. Secondary Outcome

Title	Proportion of Patients With Changes in Levels of Metalloproteinases
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

12. Secondary Outcome

Title	Proportion of Patients With Changes in Levels of beta2-microglobulin.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

13. Secondary Outcome

Title	Proportion of Patients With Changes in Levels of CSF Cells.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

14. Secondary Outcome

Title	Proportion of Patients With Changes in Levels of Proteins.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

15. Secondary Outcome

Title	Proportion of Patients With Improvement in Neuropsychological Test
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Chi-squared, Corrected
	Comments

16. Secondary Outcome

Title	Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups.
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Number [participants]	6 50%	6 60%	3 30%	6 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Chi-squared, Corrected
	Comments

17. Secondary Outcome

Title	Changes in CD4 CD38+ HLADR+ (%)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EFV/FTC/TDF	EFV/FTC/TDF + Losartan	FTC/TDF + MK-0518	FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral	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.	FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral	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.
Measure Participants	12	10	10	10
Median (Inter-Quartile Range) [percentage of CD4 T cells]	2.3	4	1.8	2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EFV/FTC/TDF, EFV/FTC/TDF + Losartan, FTC/TDF + MK-0518, FTC/TDF+MK-0518+Losartan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Arm/Group Title	EFV/FTC/TDF		EFV/FTC/TDF + Losartan		FTC/TDF + MK-0518		FTC/TDF+MK-0518+Losartan
Arm/Group Description	EFV/FTC/TDF: 600/200/245 mg, od, oral		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.		FTC/TDF + MK-0518: FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral		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.
All Cause Mortality
	EFV/FTC/TDF		EFV/FTC/TDF + Losartan		FTC/TDF + MK-0518		FTC/TDF+MK-0518+Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	EFV/FTC/TDF		EFV/FTC/TDF + Losartan		FTC/TDF + MK-0518		FTC/TDF+MK-0518+Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	EFV/FTC/TDF		EFV/FTC/TDF + Losartan		FTC/TDF + MK-0518		FTC/TDF+MK-0518+Losartan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50%)		6/10 (60%)		3/10 (30%)		6/10 (60%)
Endocrine disorders
Gynecomastia	1/12 (8.3%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/12 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Abdominal pain	0/12 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Hepatobiliary disorders
Liver tests abonormalities	1/12 (8.3%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Infections and infestations
Hepatitis C	0/12 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	2/10 (20%)	2
Sexual transmitted diseases	1/12 (8.3%)	1	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2
Musculoskeletal and connective tissue disorders
Tendinitis	1/12 (8.3%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Nervous system disorders
Post lumbar puncture headache	1/12 (8.3%)	1	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1
Headache	0/12 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Psychiatric disorders
Asthenia	0/12 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Dysthimia	1/12 (8.3%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Insomnia	0/12 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/12 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Vascular disorders
High Blood Pressure	0/12 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.