HIV Infection, HIV Infections
Conditions
Keywords
Infection, HIV 1, HIV, Losartan, Fibrosis, Immune Activation, Immune Reconstitution
Brief summary
This study was designed to test the hypothesis that treatment of HIV infected subjects with losartan, an agent with specific anti-inflammatory and anti-fibrotic actions, will: 1. reverse existing lymphoid tissue fibrosis, 2. restore lymphoid tissue architecture, 3. increase the number and improve the function of peripheral and lymphatic CD4 T cells, 4. decrease levels of systemic immune activation (IA), 5. decrease size of the HIV reservoir, and 6. be safe and well tolerated.
Detailed description
This is a randomized, double-blind, placebo-controlled trial of 50 HIV-1 infected individuals on stable ART randomized in a 1:1 ratio to losartan (50 mg orally daily titrated to 100 mg daily) vs placebo for 30 months. We plan to enroll a total of 63 HIV infected subjects to ensure that 50 complete the protocol. All HIV infected subjects will undergo biopsies of inguinal lymph node (LN) and gut associated lymphatic tissue (GALT) for primary endpoint analysis at baseline, 12 and 30 months after study enrollment. Blood will be collected at least quarterly throughout the study and an intensive blood pharmacokinetic (PK) study will be conducted at month 1. All HIV infected subjects will be vaccinated with the quadrivalent human papillomavirus (HPV) vaccine at months 23, 25 and 29.5 to measure immune function. 5 HIV uninfected control subjects will also be enrolled. The primary endpoint is to determine the impact of losartan on lymphoid tissue fibrosis in HIV infected, ART treated adults. This will be determined by measuring the amount of collagen deposition in lymphoid tissues and the integrity of the FRCn using immunohistochemistry (IHC) and quantitative image analysis (QIA).
Interventions
DRUGLosartan
Participants will start with 50 mg of losartan by mouth daily. The dose will be increased to 100 mg by mouth daily after 14 days. The maximal tolerable dosage (up to 100mg by mouth daily) will be continued for a total of 30 months.
DRUGPlacebo
one tablet by mouth daily
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Merck Sharp & Dohme LLC
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
HIV infected participants: 1. Inclusion Criteria: Participants must meet all of the following inclusion criteria to participate in this study: * HIV-1 infected. -≥ 18 years of age. * Baseline peripheral CD4+ T cell count 200-600 cells/mm3 for at least two measures over the 6 months prior to study enrollment. -≥ 12 months of stable ART, defined as use of a given drug regimen without disruption lasting ≥ 1 week in the period leading up to study enrollment. * HIV viral load (VL) \< 50 copies/mL for at least two consecutive measures over the 6 months prior to study enrollment. * No contraindication to proposed study procedures. * Women of child-bearing potential must be willing to use a form of effective contraception for the duration of the study. Effective contraception includes hormonal injection, implant or oral medication, IUD, diaphragm, or cervical cap with spermicide. Condoms cannot be used as the sole form of contraception. 2.
Exclusion criteria
Participants meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Integrity of the Fibroblastic Reticular Cell Network (FRCn) | 30 months | The Impact of Losartan Treatment on Lymphoid Tissue (LT) Fibrosis will be determined by measuring the Integrity of the fibroblastic reticular cell network (FRCn) using immunohistochemistry (IHC) and quantitative image analysis (QIA). LT will be obtained at baseline, month 12 and month 30. |
| Collagen Deposition in LT | 30 months | The Impact of Losartan Treatment on Lymphoid Tissue (LT) Fibrosis will be determined by measuring the amount of collagen deposition in LT using immunohistochemistry (IHC) and quantitative image analysis (QIA). LT will be obtained at baseline, month 12 and month 30. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency TUNEL+CD3+CD8+ T Cells | 30 months | Impact of losartan on immune reconstitution and function will be determined by frequency of TUNEL+CD3+CD8+ T cells in LT using IHC. |
| Frequency of Cells Expressing TGF-beta and Lymphotoxin-beta | 30 months | Impact of losartan on immune reconstitution and function will be determined by frequency of cells expressing TGF-beta and lymphotoxin-beta in LT using IHC. |
| Serum Concentration of IL-7 | 30 months | Impact of losartan on immune reconstitution and function will be determine by serum concentrations of IL-7 measured with ELISA. |
| Serum Concentration of TGF-beta | 30 months | Impact of losartan on immune reconstitution and function will be determine by serum concentrations of TGF-beta measured with ELISA. |
| Immune Response to HPV Vaccination | 30 months | Impact of losartan on immune reconstitution and function will be determine by measuring the immune response to HPV vaccination using flow cytometry to identify cells stimulated by specific HPV peptides. |
| Frequency of Activated T-cell Populations - Immunofluorescent Staining | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the frequency of activated T-cell populations (specifically CD3+CD4+CD38+, CD3+,CD8+CD38+,CD4+Ki67+ and CD8+Ki67+ T cells) in LT using immunofluorescence staining |
| Percent of Activated T Cells in PBMCs - Flow Cytometry | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated T cells in peripheral blood mononuclear cells (PBMCs) using flow cytometry. |
| Percent of Activated Macrophages in PBMCs - Flow Cytometry | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated macrophages in peripheral blood mononuclear cells (PBMCs) using flow cytometry. |
| Percent of Activated Dendritic Cells in PBMCs - Flow Cytometry | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated dendritic cells in peripheral blood mononuclear cells (PBMCs) using flow cytometry. |
| Percent of Activated T Cells in LT - Flow Cytometry | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated T cells in lymphoid tissues (LT) using flow cytometry. |
| Percent of Activated Macrophages in LT - Flow Cytometry | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated macrophages in lymphoid tissues (LT) using flow cytometry. |
| Percent of Activated Dendritic Cells in LT - Flow Cytometry | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated dendritic cells in lymphoid tissues (LT) using flow cytometry. |
| Intracellular Concentration of IL-17 in PBMCs | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-17 in PBMCs using cytokine staining. |
| Intracellular Concentration of IFNg in PBMCs | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IFNg in PBMCs using cytokine staining. |
| Intracellular Concentration of IL-2 in PBMCs | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-2 in PBMCs using cytokine staining. |
| Intracellular Concentration of TNF in PBMCs | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine TNF in PBMCs using cytokine staining. |
| Intracellular Concentration of IL-10 in PBMCs | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-10 in PBMCs using cytokine staining. |
| Intracellular Concentration of GM-CSF in PBMCs | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine GM-CSF in PBMCs using cytokine staining. |
| Intracellular Concentration of IL-17 in LT | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-17 in lymphoid tissue (LT) using cytokine staining. |
| Intracellular Concentration of IFNg in LT | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IFNg in lymphoid tissue (LT) using cytokine staining. |
| Intracellular Concentration of IL-2 in LT | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-2 in lymphoid tissue (LT) using cytokine staining. |
| Intracellular Concentration of TNF in LT | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine TNF in lymphoid tissue (LT) using cytokine staining. |
| Intracellular Concentration of IL-10 in LT | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-10 in lymphoid tissue (LT) using cytokine staining. |
| Intracellular Concentration of GM-CSF in LT | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine GM-CSF in lymphoid tissue (LT) using cytokine staining. |
| Plasma Concentration of LPS | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of LPS by ELISA. |
| Plasma Concentration of sCD14 | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of sCD14 by limulus assay. |
| Plasma Concentration of I-FABP | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of I-FABP using ELISA. |
| Plasma Concentration of IL-1b | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of IL-1b using ELISA. |
| Plasma Concentration of IL-1RA | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of IL-1RA using ELISA. |
| Plasma Concentration of IL-6 | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of IL-6 using ELISA. |
| Plasma Concentration of TNF | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of TNF using ELISA. |
| Plasma Concentration of Amyloid A | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of amyloid A using ELISA. |
| Plasma Concentration of CRP | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of CRP using ELISA. |
| Plasma Concentration of D-dimer | 30 months | The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of D-dimer using ELISA. |
| Frequency of HIV RNA+ and DNA+ Cells in LN - Radiolabeled ISH | 30 months | The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in LN using radiolabeled in situ hybridization (ISH). |
| Frequency of HIV RNA+ and DNA+ Cells in LN - RNAscopeTM in Situ Technology | 30 months | The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in LN using RNAscopeTM in situ technology. |
| Frequency of HIV RNA+ and DNA+ Cells in GALT - RNAscopeTM in Situ Technology | 30 months | The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in GALT using RNAscopeTM in situ technology. |
| Concentration of Losartan and Antiretrovirals (ARVs) | 30 months | Potential Drug-drug Interactions Between Losartan and Antiretrovirals (ARVs) will be assessed by measuring levels of ARVs and losartan in plasma and peripheral blood mononuclear cells (PBMCs). |
| Intracellular Concentration of Losartan and Antiretrovirals (ARVs) | 30 months | Potential Drug-drug Interactions Between Losartan and Antiretrovirals (ARVs) will be assessed by measuring intracellular concentration of losartan and ARVs in lympoidtissue. |
| Frequency of HIV RNA+ and DNA+ Cells in GALT - Radiolabeled in Situ Hybridization (ISH) | 30 months | The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in GALT radiolabeled in situ hybridization (ISH). |
| Frequency of CD4+ T Cells | 30 months | Impact of losartan on immune reconstitution and function will be determined by frequency of CD4+ T cells in LT using IHC. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Dendritic Cell and CD4 T Cell Interactions With the FRCn | 30 months | As an exploratory endpoint, we will determine the impact of losartan on frequency of dendritic cell and CD4 T cell interactions with the FRCn. This will be determined using two-photon microscopy in sections on LN obtained from study subjects. Given that this is an exploratory endpoint, these assays will be performed in a subset of subjects (5 losartan treated, 2 placebo treated and 5 HIV uninfected controls). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan Losartan: We will start with 50 mg of losartan by mouth daily. We will increase the dosage to 100 mg by mouth daily after 14 days. The maximal tolerable dosage (up to 100mg by mouth daily) will be continued for a total of 30 months. | 25 |
| Sugar Pill Placebo: one tablet by mouth daily | 27 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Sugar Pill | Total | Losartan |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 49 Participants | 23 Participants |
| Age, Continuous | 50 years STANDARD_DEVIATION 11 | 50 years STANDARD_DEVIATION 11 | 51 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 12 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 33 Participants | 19 Participants |
| Region of Enrollment United States | 27 participants | 52 participants | 25 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 26 Participants | 51 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 25 | 1 / 27 |
| other Total, other adverse events | 25 / 25 | 27 / 27 |
| serious Total, serious adverse events | 2 / 25 | 6 / 27 |
Outcome results
Primary
Collagen Deposition in LT
The Impact of Losartan Treatment on Lymphoid Tissue (LT) Fibrosis will be determined by measuring the amount of collagen deposition in LT using immunohistochemistry (IHC) and quantitative image analysis (QIA). LT will be obtained at baseline, month 12 and month 30.
Time frame: 30 months
Population: Some participant data was left out of this analysis due to sample quality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losartan | Collagen Deposition in LT | 12 months | 34.866 percent area | Standard Deviation 9.3914 |
| Losartan | Collagen Deposition in LT | 30 months | 30.8925 percent area | Standard Deviation 9.4894 |
| Sugar Pill | Collagen Deposition in LT | 12 months | 31.02 percent area | Standard Deviation 5.6795 |
| Sugar Pill | Collagen Deposition in LT | 30 months | 29.4492 percent area | Standard Deviation 6.2988 |
Primary
Integrity of the Fibroblastic Reticular Cell Network (FRCn)
The Impact of Losartan Treatment on Lymphoid Tissue (LT) Fibrosis will be determined by measuring the Integrity of the fibroblastic reticular cell network (FRCn) using immunohistochemistry (IHC) and quantitative image analysis (QIA). LT will be obtained at baseline, month 12 and month 30.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Concentration of Losartan and Antiretrovirals (ARVs)
Potential Drug-drug Interactions Between Losartan and Antiretrovirals (ARVs) will be assessed by measuring levels of ARVs and losartan in plasma and peripheral blood mononuclear cells (PBMCs).
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of Activated T-cell Populations - Immunofluorescent Staining
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the frequency of activated T-cell populations (specifically CD3+CD4+CD38+, CD3+,CD8+CD38+,CD4+Ki67+ and CD8+Ki67+ T cells) in LT using immunofluorescence staining
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of CD4+ T Cells
Impact of losartan on immune reconstitution and function will be determined by frequency of CD4+ T cells in LT using IHC.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of Cells Expressing TGF-beta and Lymphotoxin-beta
Impact of losartan on immune reconstitution and function will be determined by frequency of cells expressing TGF-beta and lymphotoxin-beta in LT using IHC.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of HIV RNA+ and DNA+ Cells in GALT - Radiolabeled in Situ Hybridization (ISH)
The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in GALT radiolabeled in situ hybridization (ISH).
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of HIV RNA+ and DNA+ Cells in GALT - RNAscopeTM in Situ Technology
The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in GALT using RNAscopeTM in situ technology.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of HIV RNA+ and DNA+ Cells in LN - Radiolabeled ISH
The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in LN using radiolabeled in situ hybridization (ISH).
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency of HIV RNA+ and DNA+ Cells in LN - RNAscopeTM in Situ Technology
The Potential for Losartan to Reduce the Size of the Viral Reservoir will be assessed by determining the frequency of HIV RNA+ and DNA+ cells in LN using RNAscopeTM in situ technology.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Frequency TUNEL+CD3+CD8+ T Cells
Impact of losartan on immune reconstitution and function will be determined by frequency of TUNEL+CD3+CD8+ T cells in LT using IHC.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Immune Response to HPV Vaccination
Impact of losartan on immune reconstitution and function will be determine by measuring the immune response to HPV vaccination using flow cytometry to identify cells stimulated by specific HPV peptides.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of GM-CSF in LT
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine GM-CSF in lymphoid tissue (LT) using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of GM-CSF in PBMCs
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine GM-CSF in PBMCs using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IFNg in LT
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IFNg in lymphoid tissue (LT) using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IFNg in PBMCs
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IFNg in PBMCs using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IL-10 in LT
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-10 in lymphoid tissue (LT) using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IL-10 in PBMCs
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-10 in PBMCs using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IL-17 in LT
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-17 in lymphoid tissue (LT) using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IL-17 in PBMCs
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-17 in PBMCs using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IL-2 in LT
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-2 in lymphoid tissue (LT) using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of IL-2 in PBMCs
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine IL-2 in PBMCs using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of Losartan and Antiretrovirals (ARVs)
Potential Drug-drug Interactions Between Losartan and Antiretrovirals (ARVs) will be assessed by measuring intracellular concentration of losartan and ARVs in lympoidtissue.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of TNF in LT
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine TNF in lymphoid tissue (LT) using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Intracellular Concentration of TNF in PBMCs
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the intracellular levels of the inflammatory cytokine TNF in PBMCs using cytokine staining.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Percent of Activated Dendritic Cells in LT - Flow Cytometry
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated dendritic cells in lymphoid tissues (LT) using flow cytometry.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Percent of Activated Dendritic Cells in PBMCs - Flow Cytometry
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated dendritic cells in peripheral blood mononuclear cells (PBMCs) using flow cytometry.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Percent of Activated Macrophages in LT - Flow Cytometry
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated macrophages in lymphoid tissues (LT) using flow cytometry.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Percent of Activated Macrophages in PBMCs - Flow Cytometry
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated macrophages in peripheral blood mononuclear cells (PBMCs) using flow cytometry.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Percent of Activated T Cells in LT - Flow Cytometry
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated T cells in lymphoid tissues (LT) using flow cytometry.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Percent of Activated T Cells in PBMCs - Flow Cytometry
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the percentage of activated T cells in peripheral blood mononuclear cells (PBMCs) using flow cytometry.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of Amyloid A
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of amyloid A using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of CRP
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of CRP using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of D-dimer
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of D-dimer using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of I-FABP
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of I-FABP using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of IL-1b
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of IL-1b using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of IL-1RA
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of IL-1RA using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of IL-6
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of IL-6 using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of LPS
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of LPS by ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of sCD14
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of sCD14 by limulus assay.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Plasma Concentration of TNF
The Impact of Losartan on Immune Activation in HIV Infected, Treated Individuals will be determined by measuring the plasma concentration of TNF using ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Serum Concentration of IL-7
Impact of losartan on immune reconstitution and function will be determine by serum concentrations of IL-7 measured with ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Secondary
Serum Concentration of TGF-beta
Impact of losartan on immune reconstitution and function will be determine by serum concentrations of TGF-beta measured with ELISA.
Time frame: 30 months
Population: This measure was planned at the time of registration, however it was not collected during the course of the trial. This data is not able to be reported.
Other Pre-specified
Frequency of Dendritic Cell and CD4 T Cell Interactions With the FRCn
As an exploratory endpoint, we will determine the impact of losartan on frequency of dendritic cell and CD4 T cell interactions with the FRCn. This will be determined using two-photon microscopy in sections on LN obtained from study subjects. Given that this is an exploratory endpoint, these assays will be performed in a subset of subjects (5 losartan treated, 2 placebo treated and 5 HIV uninfected controls).
Time frame: 30 months
Population: This exploratory endpoint was not analyzed and data are not available to be reported.