Clinical trial NCT02102451: Control and Elimination Within Australia of Hepatitis C From People Living With HIV
Official title: A Five Year Plan of Enhanced HCV Monitoring, Primary Care-Based Workforce Development, Rapid Scale-up of HCV Treatment and Public Health Policy Action in HIV Positive Individuals Within Australia.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis C
HIV
HIV-HCV Coinfection
Keywords: Interferon-free
Direct acting antiviral (DAA)
Treatment as prevention
Surveillance
Feasibility
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
First posted: 2014-04-03
Enrollment: 492
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Adults living with HIV-HCV coinfection

Brief summary: The purpose of this study is to evaluate the feasibility of rapid scale-up of new hepatitis C (HCV) treatments, known as interferon-free Direct Acting Antiviral (DAA) drugs, and impact on the proportion of people with HCV within the HIV-HCV coinfected population of Australia.

It is hypothesised that a rapid scale-up of hepatitis C treatment with interferon-free therapies in individuals with HIV-HCV coinfection will assist in controlling HCV infection in this population.

Detailed description: This project has seven 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.

Database of HIV-HCV individuals (CEASE-D):

Surveillance of HIV-HCV positive individuals will occur through the enrolment into the CEASE-D observational study database. The proportion with HCV viraemia in this population will be determined through three cross-sectional surveys; at enrolment (2014-2016), follow-up 1 (2017-2018) and follow-up 2 (2019-2020). Participation will involve providing informed consent, collection of limited clinic and demographic information, a dried blood spot sample, patient completed CEASE questionnaires and FibroScan® (where available). It is estimated that approximately 1000 HIV-HCV coinfected individuals will be enrolled into the CEASE-D database.

Modelling (CEASE-M):

Mathematical modeling will be undertaken to examine various treatment strategies, including HCV treatment scale-up timelines. The data from the first cross-sectional survey of the HCV surveillance phase (CEASE-D) will inform components of the modeling.

HCV Education for HIV prescribers (CEASE-E):

A comprehensive education program in HCV treatment with interferon-free DAA therapy will be conducted with HIV prescribers with high HCV caseloads in preparation for the rapid scale-up of HCV treatment.

HCV Treatment Scale-Up (CEASE-T):

HCV treatment scale-up with PBS listed regimens will involve primary and tertiary clinics. All patients who are commencing HCV treatment will be invited to participate in CEASE-T which will involve data collection regarding treatment with PBS listed regimens. The regimen and duration will be determined by the treating clinician according to PBS prescribing guidelines. At selected sites subjects will be offered enrollment into a more intensive follow-up substudy (I-STEP) involving collection of research EDTA plasma samples, patient completed behavioural questionnaires and FibroScan® (where available). Patients with recurrent viraemia during or following treatment (relapse/reinfection) may also be entered into a separate substudy cohort (CEASE-V)

Recurrent Viraemia Treatment (CEASE-V) At selected sites patients with on-treatment virological failure (nonresponse or viral breakthrough) or post-treatment recurrent viraemia (relapse or reinfection) will be entered into an intensive follow-up cohort (CEASE-V). Participation will involve providing informed consent, collection of research EDTA plasma samples and patient completed behavioural questionnaires. Patients may be offered retreatment with PBS listed regimens. The decision to retreat as well as the regimen and duration will be determined by the treating clinician according to PBS prescribing guidelines.

Dried Blood Spot Validation Sub-study (DBS 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 be mailed DBS self-collection kits and questionnaires to evaluate feasibility, acceptability and validity of self-collected DBS samples compared to clinic collected plasma samples. Pre and post DBS acceptability questionnaires will be completed.

Qualitative Sub-study (CEASE-Q) At selected sites patients will be invited to participate in the Qualitaitive Sub-study (CEASE-Q). Semi-structured interviews will be used to explore risk behaviour pre and post DAA therapy, participant experience of DAA therapy and, in untreated participants, facilitators and barriers to DAA therapy.

Eligibility criteria: Inclusion Criteria:

CEASE-D:

1. 18 years of age or older
2. Voluntarily signed the informed consent form
3. HIV positive
4. HCV antibody positive
5. Adequate English and mental health status to provide written informed consent and comply with study procedures

CEASE-T (ISTEP):

1. 18 years of age or older
2. Voluntarily signed the informed consent form
3. HIV positive
4. HCV RNA positive
5. Adequate English and mental health status to provide written informed consent and comply with study procedures
6. Undergoing DAA therapy HCV treatment.

CEASE-V:

1. 18 years of age or older
2. Voluntarily signed the informed consent form
3. HIV positive
4. Undergone IFN-free DAA therapy for HCV

6) On treatment virological failure or post-treatment recurrent viraemia as defined by either:

1. Non-response: Failure of viral suppression on IFN-free DAA therapy
2. Virological breakthrough on IFN-free DAA therapy
3. Post-treatment recurrent viraemia: Detectable HCV RNA post-treatment following an end-of-treatment response (ETR, undetectable HCV RNA at end of treatment)

   DBS Sub-study Population:

   1) 18 years of age or older 2) Voluntarily signed the informed consent form 3) HIV positive 4) HCV antibody positive 5) Adequate English and mental health status to provide written informed consent and comply with study procedures 6) Under follow-up within I-STEP post-treatment for HCV

   DBS Sub-study Controls:

   1) 18 years of age or older 2) Voluntarily signed the informed consent form 3) HIV negative 4) HCV antibody positive 5) Undergoing DAA therapy for HCV and requiring confirmation of SVR post therapy 6) Adequate English and mental health status to provide written informed consent and comply with study procedures

   CEASE-Q:

   1) 18 years of age or older 2) Voluntarily signed the informed consent form 3) HIV positive 4) HCV antibody positive 5) Adequate English and mental health status to provide written informed consent and comply with study procedures 6) Under follow-up within I-STEP post-treatment for HCV

   Exclusion Criteria:

   CEASE-D:

   1) Inability or willingness to comply with protocol requirements

   CEASE-T:

   1) Inability or willingness to comply with protocol requirements

   CEASE-V:

   1) Inability or willingness to comply with protocol requirements

   DBS Sub-study:

   1) Inability or willingness to comply with protocol requirements

   CEASE-Q:

   1) Inability or willingness to comply with protocol requirements

Primary outcomes:
measure: HCV viraemia
timeFrame: 5 years
Secondary outcomes:
measure: Needs, behaviour and attitudes towards HCV treatment
timeFrame: 5 years
measure: HCV treatment uptake
timeFrame: 5 years
measure: Factors associated with HCV treatment and retreatment
timeFrame: 5 years
measure: HCV treatment response rates
timeFrame: 5 years
measure: Rates of HCV retreatment
timeFrame: 5 years
measure: HCV transmission history
timeFrame: 5 years
Other outcomes:
Locations:
city: Burwood
country: Australia
facility: Dr Doong's Surgery
state: New South Wales
city: Katoomba
country: Australia
facility: Blue Mountains Sexual Health and HIV Centre
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Sexual Health Centre
state: New South Wales
city: Sydney
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Sydney
country: Australia
facility: Kirketon Road Centre
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: The Albion Centre
state: New South Wales
city: Sydney
country: Australia
facility: Western Sydney Sexual Health
state: New South Wales
city: Sydney
country: Australia
facility: Nepean Sexual Health and HIV Clinic
state: New South Wales
city: Brisbane
country: Australia
facility: Brisbane Sexual Health Clinic
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Carlton
country: Australia
facility: Melbourne Sexual Health Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: North Fitzroy
country: Australia
facility: Northside Clinic
state: Victoria
city: Prahran
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: St Kilda
country: Australia
facility: The Centre Clinic
state: Victoria
Study officials:
affiliation: Kirby Institute, University of New South Wales
name: Gail Matthews, MbChB, MRCP, FRACP, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kirby Institute, University of New South Wales
name: Greg Dore, BSc, MBBS, FRACP, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martinello M, Yee J, Bartlett SR, Read P, Baker D, Post JJ, Finlayson R, Bloch M, Doyle J, Shaw D, Hellard M, Petoumenos K, Lin L, Marks P, Applegate T, Dore GJ, Matthews GV. Moving Towards Hepatitis C Microelimination Among People Living With Human Immunodeficiency Virus in Australia: The CEASE Study. Clin Infect Dis. 2020 Sep 12;71(6):1502-1510. doi: 10.1093/cid/ciz985.