Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C
Condition: Hepatitis C, Chronic; HIV
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: Pegylated interferon alpha-2a; Ribavirin; Boceprevir
Intervention description: 180mcg once weekly; subcutaneous injection; 600mg two times daily (BID) (e.g. 3x200mg at 6am, 3x200mg at 6pm) in patients ≥75kg body weight; 2x200mg at 6am and 3x200mg at 6pm in patients <75kg; orally; 800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Boceprevir; HIV/HCV-coinfection; HIV/HCV coinfection; HIV/HCV; Response-guided therapy

Summary:

      Response-guided triple-therapy with boceprevir (BOC) in combination with pegylated interferon
      (PEGIFN) and ribavirin (RBV) is the current standard of care for HIV-negative patients
      infected with hepatitis C genotype (HCV-GT) 1. In contrast, in HIV-positive patients, a fixed
      treatment duration of 48 weeks is used.

      The aim of this study is to assess efficacy and safety of response-guided triple-therapy with
      BOC in combination with PEGIFN and RBV in HIV-positive patients. Thus, treatment duration
      will be individualized based on HCV-RNA negativity at treatment week 8 (W8). All patients
      will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at W8 will be
      treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment
      duration of 28 weeks, while patients with detectable HCV-RNA at W8 will receive 44 weeks of
      BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed HIV infection (anti-HIV1/2 antibody positive).

          -  Chronic HCV infection (anti-HCV positive, HCV-RNA detectable for >6 months).

          -  HCV-GT 1 infection.

          -  Age ≥18 years and ≤65 years.

          -  No prior treatment with BOC/PEGIFN/RBV.

          -  CD4+ cell count >200 cells/µL.

          -  Stable antiretroviral therapy (ART) including tenofovir/emtricitabine (Truvada®,
             Gilead) and raltegravir (Isentress®, MSD) with HIV-RNA <50 copies/mL.

          -  Valid result on transient elastography or liver biopsy within 6 months prior to
             enrollment.

          -  Female patients of childbearing potential must agree to use an effective contraceptive
             during treatment and for 4 months after treatment has been concluded.

          -  Male patients or their female partners must agree to use an effective contraceptive
             during treatment and for 7 months after treatment has been concluded.

        Exclusion Criteria:

          -  HCV-GT other than HCV-GT 1.

          -  Cirrhotic patients (as defined by METAVIR F4 in liver biopsy or liver stiffness >12.3
             kPa) with decompensated liver disease (Child-Pugh stage B/C).

          -  Chronic liver diseases other than hepatitis C virus infection (hepatitis B virus
             infection: HBsAg positivity, nonalcoholic steatohepatitis, autoimmune hepatitis,
             primary biliary cirrhosis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin
             deficiency, cystic fibrosis).

          -  Significant cardiac disease (ejection fraction <40% at echocardiography).

          -  Significant pulmonary disease (COPD stage GOLD III/IV).

          -  Significant renal disease (serum creatinine >1.5 mg/dL).

          -  Subjects taking medication(s) that is/are highly dependent on CYP3A4/5 for clearance,
             and for which elevated plasma concentrations are associated with serious and/or
             life-threatening events such as but not limited to, orally administered midazolam,
             pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives
             (dihydroergotamine, ergonovine, ergotamine, methylergonovine).

          -  Contraindications for boceprevir (Victrelis®, MSD), pegylated interferon alpha-2a
             (Pegasys®, Roche) or ribavirin (Copegus®, Roche), as listed in section 4.3 of the
             respective summary of product characteristics (SmPCs).

          -  Ongoing alcohol abuse (average daily alcohol consumption >50g).

          -  Ongoing illicit drug abuse.

          -  Unwillingness to give written informed consent.

          -  Pregnancy and breastfeeding.

          -  Women wishing to become pregnant.