Control and Elimination within AuStralia of HEpatitis C from people living with HIV (CEASE)
Hepatitis C (HCV) is recognised as a major contributor to co-morbidity in people with HIV. Unfortunately, HCV therapies have been largely unsuccessful within this population, and complicated by toxicity and tolerability issues, limiting the ability to deliver large scale treatment delivery and success.
Rapid development of directly acting antiviral (DAA) drugs against HCV has led to the reality of interferon-free regimens being available for the treatment of HCV. These regimens are short course and easily tolerated, and equally successful in HIV positive and negative individuals. Prescription of these regimens needs to move from the specialist liver clinic out to community-based prescribers if large scale access to treatment is to be achieved. This progression has brought about the potential reality of treatment as prevention of hepatitis c incidence in people living with HIV.
CEASE is a major national collaborative venture with the ultimate aim of controlling and eliminating HCV infection from the Australian HIV positive population. CEASE has five major components which will occur independently but are linked to the central theme of controlling and eliminating HCV infection from the majority of the Australian HIV positive population.
Primary objective: To evaluate the feasibility of rapid scale-up of interferon-free DAA treatments and impact on the proportion with HCV viraemia within the HIV-HCV population of Australia.
The study will consist of seven components as detailed below:
- CEASE-D: Surveillance of HCV
The proportion of HCV viraemia within the HIV-HCV coinfected population of Australia will be monitored through three cross-sectional visits; at enrolment (2014-2016), follow up 1 (2017-2018) and follow up 2 (2019-2020). During each cross section we will analyse the behaviours of the participants, including sexual risks, drug and alcohol use, mood and quality of life. Clinical data will be collected including a sample of blood for further research. - CEASE-M: Modelling
The data from the first cross-sectional survey of CEASE-D will be used to inform modelling to examine various treatment strategies. - CEASE-E: HCV Education for HIV Prescribers
A comprehensive education program in HCV treatment with interferon-free direct activity antiviral therapy will be conducted with HIV prescribers with high HCV caseloads in preparation for rapid scale-up of HCV treatment. - CEASE-T: HCV Treatment Scale-Up (I-STEP)
At selected sites, patients from CEASE-D who are undergoing Pharmaceutical Benefits Scheme (PBS) listed treatments will be invited to take part in a more intensive follow up substudy, I-STEP. The decision to treat as well as the regimen and duration will be determined by the treating clinician according to PBS prescribing guidelines. ISTEP will follow patients through their period on and directly following their treatment. Similar to CEASE-D we will analyse the behaviours of the participants, including sexual risks, drug and alcohol use, mood and quality of life, specifically across a shorter term during and after treatment. Clinical data will be collected including a sample of blood for further research. - CEASE-V: Recurrent Viraemia
At selected sites, patients from the I-STEP substudy who do not achieve clearance of HCV after PBS listed treatments or subsequently become reinfected post clearance will be invited to take part in CEASE-V. The decision to retreat these patients on another medication will be determined by the treating clinician. Participants in CEASE-V will provide a sample of blood across different time points for further research. - DBS Validation Sub-study
At selected sites, patients will be invited to participate in the Dried Blood Spot Validation Sub-study (DBS Sub-study). HIV/HCV study participants and HCV control participants will collect DBS samples at home for comparison to plasma samples collected in clinic. Pre and post DBS acceptability questionnaires will be completed. - Qualitative Sub-study (CEASE-Q)
At selected sites, patients will be invited to participate in semi-structured interviews exploring risk behaviour pre and post DAA therapy, experience of DAA therapy and, in untreated participants, facilitators and barriers to DAA therapy.
The study will have results from each component as detailed below:
- CEASE-D: Surveillance of HCV
Rapid scale-up of DAA’s for the treatment of HCV were made available on the PBS in March 2016. These three cross sectional visits are anticipated to demonstrate the effectiveness of treatment as prevention for HCV incidence within those coinfected with HIV by measuring prevalence and incidence of HCV among this population. Further research will be completed on the blood samples collected. - CEASE-M: Modelling
Modelling of the data presented within the first cross section of CEASE-D will provide models to examine various treatment strategies to help inform public policy. - CEASE-E: HCV Education for HIV Prescribers
CEASE-E focusses on education and training of HIV prescribers and high HCV caseload GP’s in HCV treatment. Completion of this component will result in expanding the number of HCV treatment prescribers across Australia and increasing the settings beyond the traditional tertiary clinic setting in which people with HIV/HCV coinfection can be treated for HCV. - CEASE-T: HCV Treatment Scale-Up (ISTEP)
This component of the study will also provide real world data on DAA treatment update, on-treatment and post –treatment response in the HIV/HCV coinfected population. Factors associated with treatment response will be examined including behavioural and host and viral factors. - CEASE-V: Recurrent Viraemia
CEASE-V will provide real world data on DAA treatment non-response and reinfection. Factors associated with reinfection and non-response will be examined. Re-treatment uptake and outcomes will also be provided. - DBS Sub-study
DBS Sub-study will evaluate the feasibility, acceptability and validity of self-collected DBS samples in HIV/HCV coinfected patients and HCV control patients. - CEASE-Q Sub-study
CEASE-Q will provide qualitative data on HCV treatment experience and risk behaviours associated with reinfection.
Australia, like many developed countries, has seen an increase in HCV incidence among HIV infected men who have sex with men. Australia is one of the only countries in the world where treatment using the new DAA medicines is available for all people living with hepatitis C including people with HIV infection. This unrestricted access will allow rapid scale-up of treatment. The reduction in the number of HCV infected people in Australia will also prevent further infections and move Australia closer to completely eliminating the virus from Australia.
