12 Weeks of Ledipasvir (LDV)/Sofosbuvir (SOF) With Weight-based Ribavirin vs. 24 Weeks of LDV/SOF
Condition: HIV-1 Infection; Hepatitis C
MeSH terms: Hepatitis C; Hepatitis
Intervention: Ledipasvir/sofosbuvir; Ribavirin
Intervention description: Participants were prescribed one fixed dose tablet of LDV 90 mg/SOF 400 mg orally per day.; Based on weight at entry:
For weight <75 kg, participants were prescribed 1000 mg of RBV per day, divided into two doses to be taken orally.
For weight ≥75 kg: participants were prescribed 1200 mg of RBV per day, divided into two doses to be taken orally.
Intervention MeSH terms: Ribavirin; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      People who are infected with Hepatitis C Virus (HCV) have a great chance of being cured of
      the infection when they are treated with sofosbuvir. However, in some instances, treatment
      with sofosbuvir-containing therapy does not work. It is not known if people respond to
      retreatment with sofosbuvir, after it did not work the first time. There is an important need
      to understand retreatment options in those instances. This clinical trial was done to study
      the response to two different regimens, ledipasvir/sofosbuvir and ledipasvir/sofosbuvir with
      ribavirin, and to see if they are safe and well-tolerated in HCV-infected persons whose
      previous treatment with sofosbuvir had failed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide written informed consent

          -  Documentation of non-cirrhotic or cirrhotic status

          -  HIV-1 infection

          -  HIV antiretroviral treatment status (ART), CD4+ T-cell (CD4) count and HIV-1 RNA as
             follows: (1) not on ART with CD4 count >500 cells/mm^3 within 42 days of study entry,
             (2) elite controller not on ART with CD4 >200 cells/mm^3 within 42 days of study entry
             and HIV-1 RNA <500 copies/mL on all measurements within 48 weeks prior to study entry,
             (3) on a stable protocol-approved ART with CD4 count >200 cells/mm^3 and HIV-1 RNA <50
             copies/mL within 42 days of study entry

          -  HCV GT-1 within 12 months prior to study entry

          -  Prior virologic treatment failure with SOF-containing regimen (SOF/RBV, SOF/PEG/RBV,
             and SOF/SIM)

          -  Body mass index (BMI) ≥18 kg/m^2 within 42 days prior to study entry

          -  Certain laboratory values obtained within 42 days prior to study entry

          -  Hemoglobin ≥12.0 g/dL for male, ≥11.0 g/dL for female participants

          -  Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGOT) <10
             x ULN

          -  For female participants of reproductive potential, a negative serum pregnancy test
             with a sensitivity of at least 25 mIU/mL performed at screening and within 48 hours
             prior to study entry

          -  Agreement to use at least two reliable forms of contraceptive simultaneously while
             receiving study treatment and for 6 months afterward

          -  Intention to comply with the dosing instructions and study schedule of assessments

        Exclusion Criteria:

          -  Receipt of any investigational drug or device within 60 days prior to study entry

          -  Prior exposure to a DAA other than SOF and SIM

          -  Chronic liver disease of a non-HCV etiology

          -  Presence of active or acute AIDS-defining opportunistic infections within 42 days
             prior to study entry

          -  Active, serious infection (other than HIV-1 or HCV) requiring parenteral antibiotics,
             antivirals, or antifungals within 42 days prior to study entry

          -  Hepatitis B virus (HBV) infection (defined as HBsAg positive) within 42 days prior to
             study entry

          -  History of clinically significant hemoglobinopathy

          -  Chronic current use of systemically administered immunosuppressive agents

          -  History of solid organ transplantation

          -  Current or prior history of clinical hepatic decompensation

          -  History of a gastrointestinal disorder (or postoperative condition) that could
             interfere with the absorption of the study drug

          -  History of significant or symptomatic pulmonary disease, cardiac disease, or porphyria
             that in the opinion of the investigator would interfere with the study

          -  History of difficulty with blood collection and/or poor venous access for the purposes
             of phlebotomy

          -  Active drug or alcohol use or dependence

          -  Use of any prohibited concomitant medications per the LDV/SOF product labeling, within
             42 days prior to study entry

          -  Known hypersensitivity to RBV, SOF, LDV, their metabolites, or formulation excipients
             or any other contraindication to the use of RBV, SOF or LDV

          -  Currently receiving zidovudine (ZDV), didanosine (ddI), stavudine (d4T) or tipranavir

          -  Acute HIV infection defined as the phase immediately following infection during which
             anti-HIV antibodies are undetectable

          -  Known hepatocellular carcinoma

          -  Breastfeeding or pregnancy

          -  A male participant with a pregnant female partner

          -  Receipt of colony stimulating agents, including but not limited to erythropoietin,
             within 42 days prior to study entry