The Kentucky Viral Hepatitis Treatment Study

The overarching goal of the Kentucky Viral Hepatitis Treatment Project (KeY Treat) is to increase access to treatment for the hepatitis C virus (HCV) in a rural Appalachian community in the midst of the opioid/HCV syndemic. This study seeks to examine whether removing barriers associated with accessing direct-acting antivirals (DAAs) for the treatment of HCV (high out-of-pocket costs, insurance restrictions requiring a specialist, abstinence, and significant liver damage) will significantly reduce the burden of HCV in Perry County, Kentucky. The proposed study is made possible by a significant drug donation from Gilead Sciences for sofosbuvir/velpatasvir, a 12-week, once per day, pan-genotypic DAA. KeY Treat proposes a multi-pronged approach to treating HCV using a mid-level provider model. In addition to DAA treatment, participants will be offered access to subsidized medication-assisted treatment, syringe services, and case management. Existing resources in the target community (public health, jail, hospital) will be leveraged, as well as ongoing projects dedicated to increasing access to HCV care in affected communities (ECHO, FOCUS) to answer whether removing the major barriers to HCV treatment affect access, and what barriers remain. All RNA-positive residents of Perry County, Kentucky will be eligible/recruited for study participation (N≈900), and the following specific aims will be addressed: 1) determination of HCV treatment uptake among rural residents with chronic HCV; 2) examination of the predictors of treatment completion among those enrolled in KeY Treat; 3) examination of the characteristics of participants achieving sustained virologic response (SVR, or cure); 4) establishment of long-term re-infection rates among those achieving SVR; 5) examination of 5-year reductions in incidence and prevalence of HCV in the intervention community compared with a control county in rural Kentucky; and 6) evaluate the impact and cost-effectiveness of KeY Treat using mathematical modeling. The proposed research has tremendous potential to impact public health in the rural United States. The majority of counties identified in CDC's recent HCV/HIV hotspot analysis were rural, and there is a real need to improve access to DAAs in order to prevent further HCV transmission, reduce the burden of advanced liver disease, and hepatocellular carcinoma in generations to come. Data from KeY Treat will inform policies around Medicaid/insurance restrictions for DAAs, and will deliver a much needed blueprint for the provision of HCV treatment in resource-deprived rural areas.

• Sofosbuvir/velpatasvir (Epclusa®) (Drug): The protocol is intended to follow best practices/standard of care for the treatment of HCV, with additional allowances for the investigators to apply rigorous scientific practices for the research aspects of the study. While the treatment of HCV is fairly straightforward, less is known about treating active drug users and RNA-positive individuals in rural areas. We propose eight visits, including intake, four treatment-related visits, and three visits to determine re-infection (6- and 12-months post-SVR). Because determination of medication adherence and long-term reinfection rates are not part of standard clinical practice, the rural protocol developed at the conclusion of KeY Treat will be streamlined based on findings, consisting of five or fewer clinical contacts. The drug used for treatment is Epclusa®, a 12-week, once per day, pan-genotypic DAA with a favorable side effect profile. Vosevi® will also be available in cases where participants are non-responsive or are re-infected.

Primary outcomes

• Participants Who Started HCV Treatment [Baseline through Week 12]: Participants who received at least one dose of study medication. This is measured by number of pills left and viral load.
• Participants Who Completed Treatment [Visit 6, 24 weeks post-baseline]: Treatment completion was defined as receiving all prescribed doses of medication. This is measured by pill count and viral load.
• Number of Participants With Sustained Virologic Response (SVR) [Visit 7, 50 weeks post-baseline]: Defined as undetectable viral RNA at the 12-week post-completion blood draw (SVR-12).
• Number of Participants for Follow-Up Re-Infection Assessment [Visit 8, 102 weeks post-baseline]: Defined as the presence of viral RNA at either the 6- or 12-month follow-up after achieving SVR.

Secondary outcomes

• Prevalence of HCV [Visit 8, 102 weeks post-baseline]: Prevalence of HCV in study population, measured by viral load.
• Incidence of HCV [Visit 8, 102 weeks post-baseline]: State surveillance data required to calculate HCV incidence were unavailable during the study period; therefore this outcome could not be evaluated.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* RNA positive for HCV
* Perry County residency (verified via ID card showing local address, lease, utility bill, etc.)
* 18 years of age or older

Exclusion Criteria:

* Individuals who are unable to provide consent (to be determined by local study staff in conjunction with our psychiatrist, Dr. Lofwall, a Co-I on the study)
* Individuals under 18 years of age (study drugs not FDA-approved for those <18)
* Pregnant women (unable to participate during duration of pregnancy, but encouraged to return following delivery)

Participant flow

Outcome results

• Participants Who Started HCV Treatment (Primary), Count of participants, Participants: HCV Positive Study Participants 370; Control (Pike County) 0
• Participants Who Completed Treatment (Primary), Count of participants, Participants: HCV Positive Study Participants 250; Control (Pike County)
• Number of Participants With Sustained Virologic Response (SVR) (Primary), Count of participants, Participants: HCV Positive Study Participants 233; Control (Pike County) 0
• Number of Participants for Follow-Up Re-Infection Assessment (Primary), Count of participants, Participants: HCV Positive Study Participants 8; Control (Pike County) 0
• Prevalence of HCV (Secondary), Count of participants, Participants: HCV Positive Study Participants 370; Control (Pike County) 0
• Incidence of HCV (Secondary), Count of participants, Participants

Adverse events

Time frame: From initiation of study treatment through the final follow-up visit (approximately 50 weeks post-baseline)

• Results publication: Havens JR, Schaninger T, Fraser H, Lofwall M, Staton M, Young AM, Hoven A, Walsh SL, Vickerman P. Eliminating hepatitis C in a rural Appalachian county: protocol for the Kentucky Viral Hepatitis Treatment Study (KeY Treat), a phase IV, single-arm, open-label trial of sofosbuvir/velpatasvir for the treatment of hepatitis C. BMJ Open. 2021 Jul 5;11(7):e041490. doi: 10.1136/bmjopen-2020-041490. PMID 34226208

• Study Protocol and Statistical Analysis Plan (PDF, 2018-11-26)
• Informed Consent Form (PDF, 2022-08-04)

• Jennifer Havens, PhD, Principal investigator, University of Kentucky Ctr on Drug & Alcohol Rsrch

NIH grants: R01DA047952