Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication
Condition: Cardiovascular Diseases; Hepatitis C; Hiv
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Cardiovascular Diseases
Intervention: Elbasvir / Grazoprevir Oral Tablet [Zepatier]; Cardiac MRI
Intervention description: All approved direct-acting antivirals for hepatitis C will be used as the intervention.; Cardiac MRI to assess for myocardial function and fibrosis
Intervention MeSH terms: Sofosbuvir; Grazoprevir; Ledipasvir; Velpatasvir; Elbasvir-grazoprevir drug combination; Sofosbuvir-velpatasvir drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Cardiovascular Disease

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age > or equal to 18 years old

          2. Able and willing to sign informed consent

          3. 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)

          4. If HIV+, suppressed on a stable, protocol-approved, ARV regimen for ≥ 8 weeks prior to
             starting HCV treatment

               1. 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.

               2. CD4 count >100 cells/mm3

          5. Willing to have samples stored for future use

          6. 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.

          7. 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:

          1. Decompensated liver disease (Childs Pugh B or C)

          2. Unable to comply with research study visits

          3. Poor venous access not allowing screening laboratory collection

          4. Have any condition that the investigator considers a contraindication to study
             participation

          5. Pregnant or breastfeeding woman

          6. 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.

          7. HIV+ patients with prior HCV treatment who achieved sustained virologic response
             (SVR)/ functional cure

          8. Use of a concomitant medication that is contraindicated with the use of the DAA for
             HCV treatment (per package insert)

          9. 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.

         10. Have any condition that the investigator considers a contraindication to study
             participation or not eligible per standard of care for HCV treatment

         11. 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

         12. 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.

         13. 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.

         14. Positive urine drug screen at screening. Not all patients with positive drug screen
             will be excluded; decision will be made by the PI.