Immunologic Effects of HCV Therapy With HARVONI in HCV Genotype 1 Chronically Mono-infected Active and Former IDUs
Condition: Hepatitis C
MeSH terms: Hepatitis C
Intervention: Harvoni (Fixed dose combination ledipasvir/sofosbuvir)
Intervention description: Harvoni (Fixed dose combination ledipasvir/sofosbuvir), one pill daily x 12 weeks
Intervention MeSH terms: Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HCV, injection drug use

Summary:

      The investigator's hypothesis is that active injectors will show a partial reduction in
      markers of immune activation with HCV therapy whereas non-injectors will show a more
      significant reduction in these markers, and will exhibit levels of immune activation that
      approach that seen in similarly studied healthy volunteers.This is based on observations that
      this group of investigators have made. They have shown that individuals who inject drugs have
      high level of immune activation in blood and tissue. Immune activation or chronic
      inflammation has been associated with accelerated aging, cardiovascular, renal and liver
      disease as well as CNS dysfunction. It remains unclear whether increased levels of immune
      activation are due to non-sterile injection of drugs, chronic infection with Hepatitis C,
      chronic opiate use, or perhaps combinations of all 3. To understand the potential
      contribution of infection with Hepatitis C the investigators will compare levels of immune
      activation pre- and post treatment with an all oral, one pill once daily, interferon sparing
      treatment of HCV in 2 groups of chronically HCV infected patients- one actively injecting
      with drugs and the other free of injection for at least 4 months. Immune activation
      comparisons will also include non-injecting healthy volunteers.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ability to give written informed consent in English

          2. Age≥18 and ≤55

          3. HCV antibody positive

          4. HCV RNA >1,000 copies/mL plasma

          5. HCV treatment naive

          6. HCV genotype 1a or 1b or mixed type 1

          7. AST, ALT <10x ULN

          8. Direct bilirubin <3.0

          9. Platelet count >50,000

         10. Creatinine clearance >30mL/min as estimated by Cockroft Gault

         11. Hemoglobin >10 if female, >11 if male

         12. Albumin > 2.8

         13. INR<2.0

         14. If Group A: urine dip for opiates + and active injection drug use of heroin defined as
             injecting at least 3 times per week.

         15. If Group B then no IDU for at least 4 months and a negative urine for opiates at
             screening.

         16. Venous access for phlebotomy

         17. Willingness to agree to effective contraception during the course of the study.

         18. If Group C: - negative urine for opiates at screening

               -  no recreational drug use for at least 2 years (excluding marijuana)

               -  HIV, HCV and HBV uninfected

        Exclusion Criteria:

          1. HIV infection

          2. Chronic infection with Hepatitis B

          3. Uncompensated cirrhosis

          4. Required use of:

             Anticonvulsants: carbamazepine, oxycarbazepine, phenobarbital, and phenytoin

             Antimycobacterials: rifabutin, rifampin, rifapentine

             Herbal Supplements: St. John's wort

             HIV Protease Inhibitors: tipranavir-ritonavir

             Antiarrhythmic Drugs: amiodarone (Cordarone, Nexterone, Pacerone)

          5. Any medical condition that in the opinion of the investigator would interfere with
             study participation and medical adherence

          6. Pregnancy/breast feeding

             -