A Prospective, Longitudinal Study of Endothelial Function in HIV/HCV Coinfected Subjects

Study Overview
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Brief Summary
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The CTSI-PLACE Study is a study for men and women with HIV/hepatitis C co-infection or HIV only. The study looks at the impact of having hepatitis C virus in addition to HIV on risk for cardiovascular disease. Participants will undergo non-invasive assessment of cardiovascular disease risk through measurements of endothelial function and blood biomarkers at baseline and 1 year (or 4 weeks and 24 weeks after end of HCV treatment for those that undergo HCV treatment during study follow-up).

Official Title
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Clinical and Translational Science Institute Prospective Longitudinal Assessment of Coinfected Subjects With HIV/Hepatitis C for Endothelial Function Study

Conditions
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HIV, Hepatitis C

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Men and women ≥ 18 years Hepatitis C negative or chronic hepatitis C infection Chronic HIV infection CD4+ T-cell count > 200 cells/mm3 Plasma HIV-1 RNA < 50 copies/mL On continuous and stable ART for at least 12 weeks Ability and willingness to provide written informed consent. Exclusion Criteria Known cardiovascular disease Diabetes requiring insulin therapy or hemoglobin A1c > 8% Inability to conform to requirements for PAT testing Decompensated liver disease Other known causes of significant liver disease Serious illness including acute liver-related disease and malignancy requiring systemic treatment or hospitalization within 12 weeks prior to study entry Presence of active or acute AIDS-defining opportunistic infections (OIs) within 12 weeks prior to study entry History of major organ transplantation with an existing functional graft and on immunosuppressive therapy History of known vascular or autoimmune disease Pregnancy HCV treatment (any approved or investigational agents) within 24 weeks prior to study entry Use of immune-based therapies or systemic corticosteroids within 12 weeks prior to study entry Advanced renal insufficiency as defined by glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 or treatment by dialysis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A (HIV/HCV coinfected)<br> | |
| Group B (HIV monoinfected)<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT) | Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation) | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | Serum hsCRP | Baseline | 
| Reactive Hyperemia Index (RHI) | Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation) | Week 52 | 
| Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | Serum hsCRP | Week 52 | 
| Insulin Resistance by HOMA-IR | fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405 | Baseline | 
| Insulin Resistance by HOMA-IR | fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405 | Week 52 | 
| Framingham Risk Score (FRS), 10-year Risk (%) | Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome. | Baseline | 
| Framingham Risk Score (FRS), 10-year Risk (%) | Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome. | Week 52 | 
| Change in RHI |  | Baseline to Week 52 | 
| Change in Level of Each Soluble Biomarker (Components of Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | Change in serum hsCRP level | Baseline to Week 52 | 
| Change in HOMA-IR |  | Baseline to Week 52 | 
| Change in Framingham Risk Score (10-year Risk, %) | Change in estimated 10-year risk (% risk) for developing coronary heart disease (CHD). Positive value indicates increase in estimated 10-year risk for CHD from baseline to Week 52. Negative value indicates decrease in estimated 10-year risk for CHD from baseline to Week 52. | Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelial function, cardiovascular risk, HIV, Hepatitis C, metabolic disease, inflammation