Hepatitis C Treatment to Prevent HIV, Initiate Opioid Substitution Therapy, and Reduce Risky Behavior

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.

• Evaluate model of care for HCV-infected adults with on-going opioid misuse (Other): Participants will be treated with direct-acting antivirals per standard of care and will be concomittantly be offered PreP for HIV prevention and buprenorphine for treatment of opioid-use disorder when clinically indicated

Primary outcomes

• Hepatitis C Virus (HCV) Cure (Sustained Virologic Response) [24 weeks]: Undetectable HCV viral load 12 weeks after the end of treatment

Secondary outcomes

• Uptake of HIV Pre-exposure Prophylaxis (PrEP) [24 weeks]: Number of participants who initiated PrEP between Day 0 and Week 24
• Retention on HIV PrEP [48 weeks]: Number of participants who initiated PrEP between Day 0 and Week 24 and continued on PrEP through week 48
• Uptake of Buprenorphine [24 weeks]: Number of participants who initiated on-site co-located buprenorphine between Day 0 and Week 24
• Retention in Buprenorphine Program [48 weeks]: Number of participants who initiated buprenorphine between Day 0 and Week 24 and were retained in buprenorphine treatment at week 48

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Hepatitis C Virus (HCV) Cure (Sustained Virologic Response) (Primary), Count of participants, Participants: Adults Infected With Hepatitis C Virus (HCV) 158
• Uptake of HIV Pre-exposure Prophylaxis (PrEP) (Secondary), Count of participants, Participants: HIV Negative Adults 29
• Retention on HIV PrEP (Secondary), Count of participants, Participants: HIV Negative Adults Who Initiated PrEP 8
• Uptake of Buprenorphine (Secondary), Count of participants, Participants: Adults Not on Medication for Opioid Use Disorder (MOUD) 61
• Retention in Buprenorphine Program (Secondary), Count of participants, Participants: Adults Who Initiated Buprenorphine 41

Adverse events

Time frame: Through study completion (96 weeks)

Limitations and caveats: Study conducted at two urban sites, may not be generalizable to all populations.

• Results publication: Rosenthal ES, Silk R, Mathur P, Gross C, Eyasu R, Nussdorf L, Hill K, Brokus C, D'Amore A, Sidique N, Bijole P, Jones M, Kier R, McCullough D, Sternberg D, Stafford K, Sun J, Masur H, Kottilil S, Kattakuzhy S. Concurrent Initiation of Hepatitis C and Opioid Use Disorder Treatment in People Who Inject Drugs. Clin Infect Dis. 2020 Oct 23;71(7):1715-1722. doi: 10.1093/cid/ciaa105. PMID 32009165

• Study Protocol and Statistical Analysis Plan (PDF, 2019-10-11)

• Elana Rosenthal, MD, Principal investigator, University of Maryland