This is an open label, non-randomized, observational pilot study to evaluate a model of care for treatment of hepatitis C in people with ongoing injection drug use. Participants will be treated with direct-acting antivirals (DAA) as per standard of care and will concomittantly be offered pre-exposure prophylaxis for HIV prevention and buprenorphine for treatment of opioid use disorder when clinically indicated.

Hepatitis C (HCV) is a chronic infection with significant morbidity and mortality. The development of directly acting antivirals (DAA) has dramatically improved the cure rate of HCV treatment. However, despite the availability of effective therapy, the global epidemic of HCV infection continues to be driven by people with ongoing injection drug use (PWID), who are largely excluded from HCV therapy. Several critical barriers exist preventing high-risk patients' entry to care, including (1) lack of engagement in the traditional healthcare system by marginalized patient populations, and (2) insurance restrictions due to concerns regarding treatment adherence and HCV reinfection. Furthermore, ongoing injection drug use places these individuals at high risk of HIV acquisition. However, studies have repeatedly demonstrated that pre-exposure prophylaxis (PrEP) reduces HIV acquisition and opioid substitution therapy with buprenorphine reduces HIV and HCV acquisition in PWID.

As such, we propose a comprehensive model of care to engage individuals with ongoing injection drug use in treatment of HCV, in conjunction with collocated services to prevent HIV acquisition and HCV reinfection, including pre-exposure prophylaxis and opioid substitution therapy. This pilot trial will demonstrate whether a comprehensive model of care can simultaneously treat HCV, and prevent HCV reinfection, HIV acquisition and effectively treat opioid use disorder.

Inclusion Criteria:

1. Age 18 years old

2. Able and willing to sign informed consent

3. Chronically infected with HCV, 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. Willing to have samples stored for future use

5. Ongoing injection drug use, defined as self-report of either:

   1. Phase 1 (first 100 enrolled participants) Injection non-prescription drug use within three months of screening visit or
   2. Phase 2 (enrolled participants 101-200) Use of non-prescription opioids within twelve months of screening visit

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

Adults infected with HCV and have on-going misuse with opioids

Through study completion (96 weeks)

Study conducted at two urban sites, may not be generalizable to all populations.