Elevated Cardiovascular Risk, HIV-1-infection
Conditions
Keywords
HIV, Vascular Inflammation
Brief summary
The study was conducted to determine if cenicriviroc mesylate (CVC) would decrease vascular inflammation as measured by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging of the aorta and carotid arteries.
Detailed description
This was a double-blind, placebo-controlled phase II clinical trial comparing the intervention of CVC versus placebo for a duration of 24 weeks on arterial inflammation evaluated by FDG-PET/CT imaging. A total of 110 participants were randomized 2:1 to the CVC arm (Arm A) or placebo for CVC arm (Arm B). Stratification by statin use at randomization ensured even distribution of statin use between the treatment groups. Analyses were based on the efficacy population: all enrolled participants who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications. Analysis of the primary outcome utilized multiple imputation by regression to impute missing data.
Interventions
DRUGCVC 150 mg
Administered as one 150-mg tablet by mouth once a day with food.
DRUGCVC 300 mg
Administered as two 150-mg tablets by mouth once a day with food.
OTHERPlacebo for CVC 150 mg
Administered as one 150-mg matching placebo tablets by mouth once a day with food.
OTHERPlacebo for CVC 300 mg
Administered as two 150-mg matching placebo tablets by mouth once a day with food.
Sponsors
AbbVie
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
At study entry, participants were randomized 2:1 to oral CVC (Arm A) or oral placebo for CVC (Arm B) once a day. The study treatment was added to the participants' pre-existing antiretroviral treatment (ART) regimens.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Documented to be living with HIV-1 infection. 2. Currently on a stable, continuous NNRTI-based or unboosted INSTI-based ART regimen for ≥48 weeks prior to study entry with no plans to change ART during the course of the study. 3. At least a year of controlled HIV-1 RNA levels. 4. Current CD4+ cell count \>200 cells/mm\^3. 5. Elevated cardiovascular risk defined as at least one of the following: * Clinical atherosclerotic disease (symptomatic atherosclerotic lesions in any vessel) * Subclinical atherosclerotic disease (coronary artery calcification \[CAC\] \>10 or presence of non-obstructive plaques) * Diabetes mellitus (DM) or prediabetes * Obesity * Hypertension or blood pressure ≥130/80 mmHg * Elevated LDL cholesterol (fasting LDL of \>160 mg/dL) * Low HDL cholesterol (\<40 mg/dL) * Current tobacco smoking * Family history of premature coronary artery disease (CAD) * hsCRP \>2.0 mg/L Key
Exclusion criteria
1. Acute coronary syndrome 2. A current diagnosis of latent or active tuberculosis (TB) infection 3. Current diagnosis with other intracellular pathogens (Mycobacterium avium complex, Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans). 4. Untreated hepatitis B virus (HBV) infection 5. Current hepatitis C virus (HCV) infection 6. Current, acute or clinically significant infection or illness requiring IV antibiotics or hospitalization 7. History of cirrhosis with severe hepatic impairment and/or hepatic decompensation 8. Active malignancy, except squamous cell skin cancer. 9. Hemoglobin A1c \>8% within 90 days prior to study entry. 10. Initiation of statin therapy or change in statin dose within 90 days prior to study entry. 11. Current use of any of the statins at the doses indicated: * Atorvastatin, \>40 mg/day dose * Rosuvastatin, ≥20 mg/day dose 12. Concurrent use of drugs with potential drug-drug interactions with CVC within 90 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel. | Measured at baseline and week 24 | Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standardized Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR means a reduction in the target arterial wall inflammation over time. Index vessel is the vessel with the highest vessel TBR at baseline. The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the ratio of TBR at week 24 to baseline. For the statistical analyses, results for the 6 and 9 missing values in Arm A and Arm B, respectively, were imputed using multiple imputation by regression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Measured at baseline and week 24 | Standard Uptake Value (SUV) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid). Specifically, it is the average of all evaluable SUV for a given arterial vessel. A negative number for the change in SUV implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of SUV at week 24 to baseline. |
| Change in Fasting Glucose | Measured at baseline and week 24 | Fasting glucose (mg/dL) measures the level of sugar (glucose) in the blood after fasting (no eating or drinking except water) for at least 8 hours. Higher value of change means an increase in glucose levels over time. The results are expressed as the change in fasting glucose from baseline to week 24. |
| Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | Measured at baseline and week 24 | Insulin is a hormone crucial in regulating blood sugar levels. HOMA-IR is a calculation used to assess insulin resistance and is calculated with the formula: insulin (uIU/mL) \* glucose (mg/dL) / 405. Higher value of change in insulin and HOMA-IR means an increase in insulin resistance over time. The results are expressed as the ratio of fasting insulin or HOMA-IR at week 24 to baseline. |
| Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Measured at baseline and week 24 | Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standard Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of TBR at week 24 to baseline. |
| Change in Biomarkers of Immune Activation (sCD14 and sCD163) | Measured at baseline and week 24 | The soluble proteins soluble-CD14 (sCD14, ng/mL) and soluble-CD163 (sCD163, ng/mL) are all markers of monocyte/macrophage activation. Higher value of change means an increase in the biomarker levels over time. Higher levels of sCD14 and sCD163 occur in response to inflammation and infection. The results are expressed as the difference between sCD14 or sCD163 from baseline to week 24. |
| Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | Measured at baseline and week 24 | The chemokines macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha and beta, pg/mL) as well as the chemokine, RANTES (ng/mL), are markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. RANTES and MIP-1 beta are ligands of CCR5 that were expected to increase with CVC. The results are expressed as the ratio of RANTES or MIP-1 beta at week 24 to baseline. |
| Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | Measured at baseline and week 24 | The cytokine, Interleukin-6 (IL-6, pg/mL); protein, high-sensitivity C Reactive Protein (hsCRP, mg/L); and chemokine, monocyte chemoattractant protein-1 (MCP-1, pg/mL) are all markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. MCP-1 is a ligand of CCR2 that was expected to increase with CVC. The results are expressed as the ratio of hsCRP, IL-6, or MCP-1 at week 24 to baseline. |
Countries
United States
Participant flow
Recruitment details
110 participants were enrolled from 19 US clinical research sites between May 30, 2023 and January 5, 2024.
Pre-assignment details
Participants were randomized 2:1 to CVC arm (Arm A) or placebo for CVC arm (Arm B) and stratified by statin use status (current statin use or no current statin use) at study entry (enrollment).
Participants by arm
| Arm | Count |
|---|---|
| CVC Arm (Arm A) Participants with pre-existing ART regimen of EFV took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg.
CVC 150 mg: Administered as one 150-mg tablet by mouth once a day with food.
CVC 300 mg: Administered as two 150-mg tablets by mouth once a day with food. | 74 |
| Placebo for CVC Arm (Arm B) Participants with pre-existing ART regimen of EFV took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg.
Placebo for CVC 150 mg: Administered as one 150-mg matching placebo tablets by mouth once a day with food.
Placebo for CVC 300 mg: Administered as two 150-mg matching placebo tablets by mouth once a day with food. | 36 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Efficacy Analysis Population Set | Prematurely discontinued study treatment before week 22 | 8 | 1 |
| Efficacy Analysis Population Set | Took prohibited medications | 3 | 1 |
| Study Completion | Adverse Event | 1 | 0 |
| Study Completion | Non-compliance with study drug | 1 | 0 |
| Study Completion | Took prohibited medications | 2 | 0 |
Baseline characteristics
| Characteristic | CVC Arm (Arm A) | Total | Placebo for CVC Arm (Arm B) |
|---|---|---|---|
| Age, Continuous | 58 years | 58 years | 58 years |
| Age, Customized Age Groups 45-54 | 25 Participants | 36 Participants | 11 Participants |
| Age, Customized Age Groups 55-64 | 37 Participants | 53 Participants | 16 Participants |
| Age, Customized Age Groups 65-74 | 12 Participants | 20 Participants | 8 Participants |
| Age, Customized Age Groups 75+ | 0 Participants | 1 Participants | 1 Participants |
| Antiretroviral Therapy (ART) Class INSTI and NNRTI-based | 9 Participants | 11 Participants | 2 Participants |
| Antiretroviral Therapy (ART) Class INSTI-based | 53 Participants | 80 Participants | 27 Participants |
| Antiretroviral Therapy (ART) Class NNRTI-based | 12 Participants | 19 Participants | 7 Participants |
| Aorta Vessel Standard Uptake Value (SUV) | 1.85 SUV | 1.92 SUV | 1.94 SUV |
| Aorta Vessel TBR | 2.12 Ratio | 2.10 Ratio | 2.02 Ratio |
| Bilateral Carotid Arteries Vessel SUV | 1.58 SUV | 1.65 SUV | 1.79 SUV |
| Bilateral Carotid Arteries Vessel TBR | 1.78 Ratio | 1.78 Ratio | 1.78 Ratio |
| BMI Groups Normal (18.5 - 24.9) | 16 Participants | 27 Participants | 11 Participants |
| BMI Groups Obese (30+) | 27 Participants | 44 Participants | 17 Participants |
| BMI Groups Overweight (25 - 29.9) | 31 Participants | 39 Participants | 8 Participants |
| BMI Groups Underweight (< 18.5) | 0 Participants | 0 Participants | 0 Participants |
| Body Mass Index (BMI) | 28.5 kg/m^2 | 28.5 kg/m^2 | 28.7 kg/m^2 |
| CD4 Count | 656 cells/mm^3 | 666 cells/mm^3 | 681 cells/mm^3 |
| CD4 Percent | 35.3 % | 34.8 % | 34.0 % |
| Count of High-Risk Cardiovascular Risk Factors Four or more | 23 Participants | 38 Participants | 15 Participants |
| Count of High-Risk Cardiovascular Risk Factors One | 12 Participants | 16 Participants | 4 Participants |
| Count of High-Risk Cardiovascular Risk Factors Three | 18 Participants | 28 Participants | 10 Participants |
| Count of High-Risk Cardiovascular Risk Factors Two | 21 Participants | 28 Participants | 7 Participants |
| C-Reactive Protein (hsCRP) | 1.44 mg/L | 1.71 mg/L | 2.69 mg/L |
| eGFR Groups < 60 | 3 Participants | 6 Participants | 3 Participants |
| eGFR Groups 60 - < 90 | 39 Participants | 64 Participants | 25 Participants |
| eGFR Groups 90+ | 32 Participants | 40 Participants | 8 Participants |
| Estimated Glomerular Filtration Rate (eGFR) | 86 mL/min/1.73m^2 | 82 mL/min/1.73m^2 | 77 mL/min/1.73m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 21 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 89 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting Glucose | 95 mg/dL | 95 mg/dL | 95 mg/dL |
| Fasting Insulin | 9.02 uIU/mL | 9.90 uIU/mL | 10.4 uIU/mL |
| Gender Identity Cisgender | 72 Participants | 108 Participants | 36 Participants |
| Gender Identity Transgender Spectrum | 2 Participants | 2 Participants | 0 Participants |
| HIV-1 RNA < Lower Limit of Quantification (LLQ) | 70 Participants | 101 Participants | 31 Participants |
| HIV-1 RNA ≥ Lower Limit of Quantification (LLQ) | 4 Participants | 9 Participants | 5 Participants |
| Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | 2.01 HOMA-IR Index | 2.35 HOMA-IR Index | 2.50 HOMA-IR Index |
| Index Vessel Aorta | 45 Participants | 68 Participants | 23 Participants |
| Index Vessel Left Carotid Artery | 6 Participants | 9 Participants | 3 Participants |
| Index Vessel Right Carotid Artery | 7 Participants | 13 Participants | 6 Participants |
| Index Vessel Most-Diseased Segment (MDS) Target-to-Background Ratio (TBR) | 2.26 Ratio | 2.23 Ratio | 2.22 Ratio |
| Interleukin-6 | 1.57 pg/mL | 1.79 pg/mL | 2.02 pg/mL |
| Left Carotid Artery Vessel TBR | 1.75 Ratio | 1.76 Ratio | 1.80 Ratio |
| MCP-1 | 171 pg/mL | 175 pg/mL | 184 pg/mL |
| MIP-1 alpha < Lower Limit of Quantification (LLQ) | 58 Participants | 91 Participants | 33 Participants |
| MIP-1 alpha Missing | 1 Participants | 2 Participants | 1 Participants |
| MIP-1 beta < Lower Limit of Quantification (LLQ) | 10 Participants | 14 Participants | 4 Participants |
| MIP-1 beta ≥ Lower Limit of Quantification (LLQ) | 48 Participants | 77 Participants | 29 Participants |
| MIP-1 beta Missing | 1 Participants | 2 Participants | 1 Participants |
| MIP-1 beta | 52.1 pg/mL | 52.4 pg/mL | 55.3 pg/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 38 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 46 Participants | 70 Participants | 24 Participants |
| RANTES | 69.7 ng/mL | 69.7 ng/mL | 70.2 ng/mL |
| Right Carotid Artery Vessel TBR | 1.81 Ratio | 1.81 Ratio | 1.82 Ratio |
| Sex: Female, Male Female | 23 Participants | 30 Participants | 7 Participants |
| Sex: Female, Male Male | 51 Participants | 80 Participants | 29 Participants |
| Soluble CD14 | 1403 ng/mL | 1415 ng/mL | 1435 ng/mL |
| Soluble CD163 | 729 ng/mL | 729 ng/mL | 720 ng/mL |
| Statin-use at Entry Current-use of Statins | 42 Participants | 61 Participants | 19 Participants |
| Statin-use at Entry No Current-use of Statins | 32 Participants | 49 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 36 |
| other Total, other adverse events | 44 / 74 | 20 / 36 |
| serious Total, serious adverse events | 4 / 74 | 2 / 36 |
Outcome results
Primary
Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel.
Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standardized Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR means a reduction in the target arterial wall inflammation over time. Index vessel is the vessel with the highest vessel TBR at baseline. The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the ratio of TBR at week 24 to baseline. For the statistical analyses, results for the 6 and 9 missing values in Arm A and Arm B, respectively, were imputed using multiple imputation by regression.
Time frame: Measured at baseline and week 24
Population: Efficacy population: all enrolled participants who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel. | 0.95 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel. | 0.93 Fold-change |
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel, adjusting for statin-use. The study was powered to detect a between-group difference of 0.046 in log10 MDS TBR (10% relative fold-change), assuming a null difference of 0 in log10 MDS TBR (a ratio of 1 in absolute-scale), a standard deviation of 0.065 of change in log10 TBR, and 75 evaluable participants.p-value: 0.6595% CI: [0.916, 1.056]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel differently by statin-use at study entry (use versus no-use).p-value: 0.4Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel differently by sex (female versus male).p-value: 0.63Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the MDS of the index vessel differently by race (Black/African-American versus Non-Black/African-American).p-value: 0.71Regression, Linear
Secondary
Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs)
Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standard Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of TBR at week 24 to baseline.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Aorta TBR | 1.00 Fold-change |
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Bilateral Carotid TBR | 0.99 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Aorta TBR | 0.99 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs) | Bilateral Carotid TBR | 1.02 Fold-change |
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the aorta adjusting for statin-use.p-value: 0.9195% CI: [0.93, 1.067]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the right and left carotid arteries adjusting for statin-use.p-value: 0.6495% CI: [0.901, 1.066]Regression, Linear
Secondary
Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1)
The cytokine, Interleukin-6 (IL-6, pg/mL); protein, high-sensitivity C Reactive Protein (hsCRP, mg/L); and chemokine, monocyte chemoattractant protein-1 (MCP-1, pg/mL) are all markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. MCP-1 is a ligand of CCR2 that was expected to increase with CVC. The results are expressed as the ratio of hsCRP, IL-6, or MCP-1 at week 24 to baseline.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | hsCRP | 0.85 Fold-change |
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | Interleukin-6 | 0.99 Fold-change |
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | MCP-1 | 5.00 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | hsCRP | 0.84 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | Interleukin-6 | 1.10 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1) | MCP-1 | 0.99 Fold-change |
Comparison: Evaluates whether CVC, compared to placebo, changes levels of hsCRP adjusting for statin-use.p-value: 0.9195% CI: [0.62, 1.52]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes the levels of IL-6 adjusted for statin-use.p-value: 0.9495% CI: [0.77, 1.33]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes the levels of MCP-1 adjusting for statin-use.p-value: <0.00195% CI: [3.89, 5.77]Regression, Linear
Secondary
Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)
Insulin is a hormone crucial in regulating blood sugar levels. HOMA-IR is a calculation used to assess insulin resistance and is calculated with the formula: insulin (uIU/mL) \* glucose (mg/dL) / 405. Higher value of change in insulin and HOMA-IR means an increase in insulin resistance over time. The results are expressed as the ratio of fasting insulin or HOMA-IR at week 24 to baseline.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | Fasting insulin | 0.91 Fold-change |
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | HOMA-IR | 0.85 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | Fasting insulin | 0.89 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | HOMA-IR | 0.90 Fold-change |
Comparison: Evaluates whether CVC, compared to placebo, changes levels of fasting insulin adjusting for statin-use.p-value: 0.6295% CI: [0.81, 1.43]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes levels of HOMA-IR adjusting for statin-use.p-value: 0.6195% CI: [0.78, 1.54]Regression, Linear
Secondary
Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta)
The chemokines macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha and beta, pg/mL) as well as the chemokine, RANTES (ng/mL), are markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. RANTES and MIP-1 beta are ligands of CCR5 that were expected to increase with CVC. The results are expressed as the ratio of RANTES or MIP-1 beta at week 24 to baseline.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | MIP-1 beta | 2.44 Fold-change |
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | RANTES | 0.98 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | MIP-1 beta | 1.07 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta) | RANTES | 1.06 Fold-change |
Comparison: Evaluates whether CVC, compared to placebo, changes the levels of MIP-1 beta adjusting for statin-use.p-value: <0.00195% CI: [1.28, 2.12]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes levels of RANTES adjusting for statin-use.p-value: 0.8595% CI: [0.82, 1.28]Regression, Linear
Secondary
Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta
Standard Uptake Value (SUV) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid). Specifically, it is the average of all evaluable SUV for a given arterial vessel. A negative number for the change in SUV implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of SUV at week 24 to baseline.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Aorta SUV | 1.00 Fold-change |
| CVC Arm (Arm A) | Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Bilateral Carotid SUV | 1.02 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Aorta SUV | 1.00 Fold-change |
| Placebo for CVC Arm (Arm B) | Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta | Bilateral Carotid SUV | 1.00 Fold-change |
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the aorta adjusting for statin-use.p-value: 0.7995% CI: [0.939, 1.087]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes arterial inflammation in the right and left carotid arteries adjusting for statin-use.p-value: 0.6995% CI: [0.935, 1.106]Regression, Linear
Secondary
Change in Biomarkers of Immune Activation (sCD14 and sCD163)
The soluble proteins soluble-CD14 (sCD14, ng/mL) and soluble-CD163 (sCD163, ng/mL) are all markers of monocyte/macrophage activation. Higher value of change means an increase in the biomarker levels over time. Higher levels of sCD14 and sCD163 occur in response to inflammation and infection. The results are expressed as the difference between sCD14 or sCD163 from baseline to week 24.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CVC Arm (Arm A) | Change in Biomarkers of Immune Activation (sCD14 and sCD163) | Soluble CD14 | -16.2 ng/mL |
| CVC Arm (Arm A) | Change in Biomarkers of Immune Activation (sCD14 and sCD163) | Soluble CD163 | -21.8 ng/mL |
| Placebo for CVC Arm (Arm B) | Change in Biomarkers of Immune Activation (sCD14 and sCD163) | Soluble CD14 | 6.66 ng/mL |
| Placebo for CVC Arm (Arm B) | Change in Biomarkers of Immune Activation (sCD14 and sCD163) | Soluble CD163 | 17.4 ng/mL |
Comparison: Evaluates whether CVC, compared to placebo, changes levels of sCD14 adjusting for statin-use.p-value: 0.3895% CI: [-158, 60]Regression, Linear
Comparison: Evaluates whether CVC, compared to placebo, changes the levels of sCD163 adjusting for statin-use.p-value: 0.8895% CI: [-87, 75]Regression, Linear
Secondary
Change in Fasting Glucose
Fasting glucose (mg/dL) measures the level of sugar (glucose) in the blood after fasting (no eating or drinking except water) for at least 8 hours. Higher value of change means an increase in glucose levels over time. The results are expressed as the change in fasting glucose from baseline to week 24.
Time frame: Measured at baseline and week 24
Population: Efficacy population with evaluable records: all enrolled participants with evaluable records who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CVC Arm (Arm A) | Change in Fasting Glucose | 1.00 mg/dL |
| Placebo for CVC Arm (Arm B) | Change in Fasting Glucose | -0.50 mg/dL |
Comparison: Evaluates whether CVC, compared to placebo, changes levels of fasting glucose adjusting for statin-use.p-value: 0.4995% CI: [-4.6, 9.6]Regression, Linear