Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication

Study Overview
=================
Brief Summary
-----------------
This is an interventional, non-randomized, controlled prospective study to treat HCV in mono-infected and HIV co-infected individuals and compare cardiovascular risk outcomes to HIV mono-infected controls. This pilot study will demonstrate whether functional cure of HCV reduces myocardial injury and risk of cardiovascular disease.

Official Title
-----------------
Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication

Conditions
-----------------
Cardiovascular Diseases, Hepatitis C, Hiv

Intervention / Treatment
-----------------
* Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]
* Procedure: Cardiac MRI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > or equal to 18 years old Able and willing to sign informed consent Chronically infected with any HCV genotype (1a, 1b, 2, 3, 4, 5, or 6), defined as any individual with documentation of positive HCV antibody and positive HCV RNA test (HCV RNA of 2,000 IU/mL or greater) If HIV+, suppressed on a stable, protocol-approved, ARV regimen for ≥ 8 weeks prior to starting HCV treatment HIV RNA < 50 copies/mL (or < LLOQ if the local laboratory assay's LLOQ is ≥50 copies/mL) prior to Screening. Subjects with an isolated or unconfirmed HIV RNA > 50 copies/mL (or > LLOQ if the local laboratory assay's LLOQ is ≥50 copies/mL) are not excluded. CD4 count >100 cells/mm3 Willing to have samples stored for future use If tested positive for NS5A resistance-associated polymorphisms or PEG-IFN and ribavirin experienced, able to tolerate ribavirin-containing regimen for 16 weeks. Ribavirin will be administered at the discretion of the PI. Women of childbearing potential who receive ribavirin will have to be willing to commit to abstinence from sexual activity, or use of two forms of contraceptive during treatment and for the 6 months after completion of ribavirin. Men receiving ribavirin who are sexually active with women will also have to be willing to commit to abstinence from sexual activity, or use of two forms of contraceptive during treatment and for the 6 months after completion of ribavirin. Exclusion Criteria: Decompensated liver disease (Childs Pugh B or C) Unable to comply with research study visits Poor venous access not allowing screening laboratory collection Have any condition that the investigator considers a contraindication to study participation Pregnant or breastfeeding woman Prior HCV treatment with Direct-Acting Antivirals. Note: Patients who are treatment-experienced with PEG-IFN/RBV will not be excluded; their inclusion in the study will be considered by the PI. HIV+ patients with prior HCV treatment who achieved sustained virologic response (SVR)/ functional cure Use of a concomitant medication that is contraindicated with the use of the DAA for HCV treatment (per package insert) Coinfection with HCV and HBV, in partcular HBsAg + patients. a. Patients with HBcAb+ will not be excluded, but will have HBV DNA levels checked and will be monitored while on DAA therapy and medically managed as considered appropriate by the PI. Have any condition that the investigator considers a contraindication to study participation or not eligible per standard of care for HCV treatment Patients with the following devices are excluded from participating in the cardiovascular MRI study: Central nervous system aneurysm clip Implanted neural stimulator Implanted cardiac pacemaker or defibrillator Cochlear implant Ocular foreign body (e.g. metal shavings) Implanted insulin pump Metal shrapnel or bullet The following groups of people are also excluded from participating in the cardiovascular MRI study: Patients with stable renal disease (estimated glomerular filtration rate (eGFR)<30ml/min/1.73m2 body surface area. The eGFR must be within two weeks of the the MRI exam. Patients with acute renal disease. Patients who choose to have the cardiac MRI and are over 60 years of age, have a history of renal failure, or have type I or II diabetes mellitus must have laboratory tests the same day as the MRI exam. Positive urine drug screen at screening. Not all patients with positive drug screen will be excluded; decision will be made by the PI.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HIV Mono-Infected<br>Patients infected with HIV only, and not currently or previously infected with hepatitis C. | Procedure: Cardiac MRI<br>* Cardiac MRI to assess for myocardial function and fibrosis<br>|
| Experimental: Hepatitis C Mono-Infected<br>Patients infected with Hepatitis C and have no evidence of active HIV or hepatitis B infection | Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]<br>* All approved direct-acting antivirals for hepatitis C will be used as the intervention.<br>* Other names: Sofosbuvir/Velpatasvir/Voxilaprevir;Procedure: Cardiac MRI<br>* Cardiac MRI to assess for myocardial function and fibrosis<br>|
| Experimental: HIV and Hepatitis C Co-Infected<br>Patients co-infected with HIV and hepatitis C, and have no evidence of active hepatitis B infection. | Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]<br>* All approved direct-acting antivirals for hepatitis C will be used as the intervention.<br>* Other names: Sofosbuvir/Velpatasvir/Voxilaprevir;Procedure: Cardiac MRI<br>* Cardiac MRI to assess for myocardial function and fibrosis<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiovascular Disease Risk From Baseline to After Functional Cure of Hepatitis C, as Measured by High-sensitivity C-reactive Protein | Change in high-sensitivity C-reactive protein | Baseline to 72 weeks after functional cure of HCV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Troponin I and Troponin T From Baseline to After Functional Cure of Hepatitis C | Change in the cardiac biomarkers Troponin I and Troponin T | Baseline to 48 weeks after functional cure of HCV | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cardiovascular Disease