The main purpose of the study is to evaluate the efficacy, safety and tolerability of a medication, ledipasvir/sofosbuvir (LDV/SOF), used to treat individuals with chronic hepatitis C virus (HCV) in Rwandan adults. A sub-cohort of participants will have limited laboratory monitoring to determine the minimum laboratory tests necessary.

This is an open-label single arm study that will evaluate the antiviral efficacy, safety and tolerability of ledipasvir/sofosbuvir fixed dose combination administered for 12 weeks in HCV treatment-naive and treatment-experienced participants with chronic genotype 1 or 4 HCV infection. Approximately 240 participants will be enrolled and treated with sofosbuvir (SOF) 400 mg/LDV 90 mg fixed dose combination (FDC) one tablet once daily for 12 weeks in the SHARED 1 study. Sixty additional participants will be enrolled in the SHARED 2 sub-cohort with laboratory monitoring blinded to study clinicians.

Inclusion Criteria:

• patients that are willing and able to provide written informed consent
• age ≥ 18 years
• HCV RNA ≥ 103 IU/mL
• HCV genotype 1 or 4
• screening ultrasound excluding hepatocellular carcinoma (HCC)
• acceptable laboratory values (hemoglobin ≥8.0 g/dL, platelet count ≥40,000/mm3; AST, ALT, and alkaline phosphatase ≤10 × ULN; creatinine clearance ≥30 mL/min)
• general good health
• ability to comply with study procedures
• HIV-infected patients must have completed at least 6 months of any approved HIV antiretroviral therapy (ART) per Rwanda National Guidelines 2013, have been taking for at least 2 weeks prior to screening ART compatible with SOF/LDV (efavirenz, rilpivirine, raltegravir, dolutegravir, emtricitabine, lamivudine, zidovudine, tenofovir), have screening HIV RNA < 200 copies/mL, and have screening CD4 T-cell count of ≥100 cells/µL

Exclusion Criteria:

• current or history of clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
• active tuberculosis
• other clinically-significant illness (except HCV and/or HIV) or any other major medical disorder
• active Hepatitis B infection
• difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
• any IFN-containing regimen within 8 weeks prior to screening or any prior exposure to HCV-specific direct-acting antiviral agent (other than a NS3/4A protease inhibitor and SOF), current pregnancy or breastfeeding, and active drug or alcohol use or dependence

The study protocol, study data, data dictionary, data collection instruments, and informed consent forms are available upon request from the corresponding author. De-identifiable individual participant data will be made available 9 months after the publication date and ending 36 months after the publication date. Forms and data can be accessed by written request to the corresponding author and the study sponsor, Partners In Health. The data will be made available following evaluation and approval of proposed use by the study sponsor and signed data access agreement with the study sponsor.

De-identifiable individual participant data will be made available 9 months after the publication date and ending 36 months after the publication date.

Forms and data can be accessed by written request to the corresponding author and the study sponsor, Partners In Health.

The data will be made available following evaluation and approval of proposed use by the study sponsor and signed data access agreement with the study sponsor.