Title: An exploratory sequential mixed-methods study: Using novel technologies to improve community-based hepatitis C linkage to care and treatment in the homeless population of London
Funder: Department of Health and Social Care

Abstract: Is it feasible to conduct a study of randomisation to point-of-care (POCT) hepatitis C virus(HCV) RNA for single-visit diagnosis and then to video-observed-therapy(VOT) for treatment support? Background: HCV disproportionately affects hard-to-reach groups. The prevalence is 52% in people who inject drugs and 32% in the homeless. The current HCV cascade shows poor linkage to care, with significant loss-to-follow-up.It can take several visits to confirm HCV diagnosis. HCV-antibody testing is the first step, but >75% will have current infection which requires further confirmatory laboratory-based testing for HCV-RNA. Many patients are lost-to-follow-up while waiting for HCV-RNA results. In the homeless population, only 18% engage with care after screening. POCT HCV-RNA testing, now available, can confirm current HCV infection inThere is lower treatment prescribing in hard-to-reach groups because of concerns around non-completion and development of treatment resistance. In those prescribed treatment, there are higher rates of non-completion due to complex psychosocial factors and structural barriers to care. Treatment support may allay clinicians' fears with respect to prescribing treatment, and help patients complete the full course. VOT has been used successfully to improve adherence to tuberculosis treatment in the homeless. It is acceptable and cost-effective. It could improve HCV treatment outcomes.Aims: To assess the feasibility of conducting a randomised-control-trial to POCT HCV-RNA and VOT in the homeless population of London and their cost-effectiveness, using exploratory-sequential mixed-methods research.Objectives To determine the: Acceptability of randomisation to these interventions. Practicalities of implementing the interventions including assessing the sensitivity of POCT HCV-RNA is not lower than expected in the outreach setting Cost-effectiveness of POCT HCV-RNA and VOT in full scale trialStudy design: I will conduct an exploratory sequential mixed methods study, using qualitative and quantitative assessments of POCT HCV-RNA for single-visit diagnosis and VOT for HCV treatment adherence support. I will also develop a cost-effectiveness model of a full-scale trial of these interventions, to assess feasibility. Qualitative study: interviews and focus groups. intervention study with randomisation to standard of care(SOC) test OR POCT HCV-RNA and SOC and then to VOT or no-VOT in those with confirmed infection. Cost-effectiveness analyses Outcomes:The proportion who agree to be randomised to POCT HCV-RNA and then to VOT. The feasibility of randomisation and implementation and he sensitivity of POCT HCV-RNA in this setting Cost-effectiveness of POCT HCV-RNA and VOT of a full-scale trial Timelines for delivery: Year 1:receive regulatory and ethics approval, implementation and analysis of qualitative study, implement the intervention study. Year 2:complete study recruitment and follow-up, cost-effectiveness modelling. Year 3:complete quantitative data analysis, write-up the thesis and begin to disseminate findings.Anticipated impact: These results will inform a future study to assess a new HCV care pathway, to improve cure rates in hard-to-reach groups. Harm-minimisation advice will be provided using study resources, which can be used beyond the study.Dissemination: Lay: verbal, written/online information. Clinician, commissioners, policy makers: presentation at local treatment network meetings and commissioning groups. Academic: conference presentations; publication in peer-reviewed journals.

Lay abstract: Background and aims Hepatitis C virus infection(HCV) is a common condition caused by a blood-borne virus. In England the highest risk is in those who inject drugs; the disease is present in 50% of people in this group, of whom 50% are unaware of their infection. HCV affects the liver, and untreated infection leads to liver cirrhosis and cancer. This can be prevented by people being treated and cured of the infection.If someone picks up HCV, they will develop a marker in the blood called antibody. Finding this in a blood sample or mouth swab is the first step to diagnosing HCV. However, approximately 25% of people who have the antibody will have naturally cleared the infection already and no virus will be present. A second test is needed to confirm the persistence of virus. While the antibody test can be carried out by the patient's side, the test for presence of virus is done in a laboratory and can take several weeks for a result to come back. Many people from socially excluded groups do not return for the results, and the proportion of them that start and complete HCV treatment is less than 5%.People from these groups are vulnerable and may have chaotic lives because of poverty, homelessness and drug and alcohol use. This may make it difficult for them to complete treatment without support.New technologies to diagnose HCV in one-step and to provide treatment support may result in more people coming back and completing treatment. There is a test that can check for the presence of the virus in The aim of the study is to identify if people are willing to take part in the study, if they are happy to be randomly assigned to whether they have each intervention or not and if it is practical and possible to implement the study.Who can participate? People >16 years and HCV antibody-positive and do not have HIV and/or hepatitis B infection. For the VOT part of the study, they must have confirmed HCV infection. Where? The pan-London Find-and-Treat service, provides blood-borne virus screening to the homeless population. What does the study involve? People who agree to participate will be randomly-assigned to having standard of care HCV testing OR the HCV-point-of-care-test and standard of care testing. Those who have confirmed infection will then be randomly-assigned to having VOT to help them complete the course of treatment OR no-VOT. Benefits: Participants will receive information about HCV treatment and reducing the risk of giving the virus to someone else or getting it and a small food package at their enrolment (as with prior NIHR-funded studies).Patient and Public Involvement: I have consulted with people who use the Find-and-Treat-service, members of the Hepatitis C Trust and the Find and Treat team. I understand that this is a vulnerable population, and will take steps to ensure that consent is truly informed.How will findings be publicised: Service users and participants; verbal and written information. Wider audience; The Hepatitis C Trust will publish findings online. Clinicians, commissioners and policy makers; presentations. Academics; publication in peer reviewed journals and presentations at conferences.

Research activity codes: 4.4 POPULATION SCREENING
Health categories: INFECTION