Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03740906 |
| Other study ID # |
VHCRP1606 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 6, 2019 |
| Est. completion date |
March 31, 2022 |
Study information
| Verified date |
April 2022 |
| Source |
Kirby Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
SHARP-P is an observational cohort study investigating the effect of direct-acting antiviral
(DAA) therapy and reinfection in people with chronic hepatitis C virus (HCV) and recent
injecting drug use. A prospective, observational cohort design will be used to enrol patients
from correctional centres in New South Wales, Australia.
Participants will be prescribed a direct-acting HCV medication as per the standard of care.
The on treatment phase will vary dependent on the type of a direct-acting antiviral
prescribed as per the standard of care. Once patients have completed their treatment course
they will be followed up every 3 months for up to 3 years following the end of treatment
phase.
The study will aim to evaluate the incidence of HCV reinfection following successful DAA
treatment over the three years of follow up. The study will also evaluate the proportion of
patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) with
direct-acting anti-viral HCV therapy.
Description:
In Australia, hepatitis C virus (HCV)-related morbidity and mortality have doubled in the
past decade, with health care costs of $220 million per annum associated with approximately
200,000 chronically infected cases. The majority of new (90%) and existing (80%) cases of HCV
infection occur among people who inject drugs (PWID).
As there is a close relationship between imprisonment, injecting drug use, and HCV, in any
given year, almost 20,000 of those with chronic HCV in Australia spend time in prison,
including approximately 8,000 in New South Wales (NSW). These individuals are likely to
represent the most marginalised and 'hard-to-access' subgroup of the affected population. In
addition, the prison environment is a key venue for ongoing transmission. Amongst PWID in the
prison setting the report of any injecting drug use decreased from 71% prior to prison entry
to 27% following imprisonment. However, among people who reported injecting drug use, the
proportion reporting sharing a needle/syringe increased from 29% prior to prison entry to
73%. In the community, 15-20% of current PWID report recent (last month) receptive
needle/syringe sharing.
In prison, where there is no access to formal needle and syringe programs, sharing injecting
equipment can be normative with inmates' accounts of injecting practice revealing few ways
that they can minimise HCV risk. Establishing effective disease prevention in the prison
context is challenging, as prisons are unique in physical structure, and prisoners form a
distinct micro-society with their own rules and regulations. Many health problems amongst
prisoners arise directly from conditions of imprisonment such as overcrowding, uncontrolled
exposure to violence and illicit drugs, lack of purposeful activity, separation from family
networks and emotional deprivation.
The existing strategies for HCV prevention in NSW prisons are delivered by Justice Health &
Forensic Mental Health and Corrective Services. Justice Health & Forensic Mental Health
provides a targeted screening program for blood-borne virus infection with pre- and post-test
counselling, and opioid substitution treatment (OST) for those who are opioid dependent.
Corrective Services provides bleach (or the quaternary amine disinfectant, Fincol) to clean
used syringes. NSP is not available.
Despite these efforts, in the Hepatitis C Incidence and Transmission Study in prisons
(HITS-p; n=590) led by CI-Lloyd, half of the cohort (49%) of PWID reported injecting drug use
during follow-up in prison and 31% reported sharing injecting equipment. HCV incidence was
14.1/100 p-yrs (95% CI: 9.96, 19.3). There was no apparent protective effect of bleach
cleansing or OST, highlighting the additional challenges of HCV prevention in the custodial
setting.
Qualitative research shows that decisions about sharing equipment are multi-factorial and can
include issues ranging from service access (such as distance to service and opening hours),
concerns about anonymity, perceptions that HCV is ubiquitous and unavoidable to
socially-located concerns that promote use of sterile equipment such as a desire to avoid
"track marks". In the prison context, complex social, economic, and environmental risk
factors contributed to injecting practices with the person supplying the drugs injecting
first, and the person who owns the injecting equipment going next. Risk of HCV acquisition
did not regularly factor into determining order of injection within networks. There is no
research that examines sharing of injecting equipment in those who have been cured with
antiviral therapy in either community or prison settings.
Increasing access to HCV therapy is a key objective of national and NSW Hepatitis C
Strategies. The advent of well-tolerated, simple, oral hepatitis C virus (HCV) regimens -
direct acting antivirals (DAAs) - has the potential to transform this landscape. These are
much shorter, tolerable treatment regimens with cure rates >95%, providing an opportunity to
reverse the rising burden of advanced liver disease. From 1st March 2016, these highly
efficacious HCV therapies have been listed on the Pharmaceutical Benefit Scheme, and people
with recent injecting drug use including prisoners are eligible to receive them. These are
important features of the listing. In many countries, people who have not ceased injecting
drug use are ineligible to receive DAA therapy, despite the fact that they comprise a
significant proportion of HCV cases. Australia is therefore is leading the world in the
scale-up of new therapies to an extent that many countries with such exclusions will not be
able to achieve.
This feature of DAA access also affords unique opportunities with respect to the
implementation of treatment scale-up in community drug treatment clinics and prisons.
Australia has good treatment coverage for people who are opioid dependent, with over 50% of
opioid dependent people estimated to engage in opioid substitution therapy (OST).
Community-based drug treatment clinics and prisons represent a logical venue for expansion of
HCV care beyond existing tertiary HCV treatment centres.
Although response to DAA HCV therapy is high, lower responses have been observed among people
with previous treatment experience, cirrhosis and those with baseline or emergent resistance
associated variants. Such resistance associated variants can persist for up to two years
after treatment, affect re-treatment options, and be transmitted to new hosts. Further, PWID
are likely to be exposed to multiple HCV infections as a result of ongoing high-risk
behaviours and might commonly harbour mixed HCV infections (infection with two or more
distinct viruses). Underlying mixed HCV infection can contribute to nonresponse during
therapy, which has implications for DAA regimens that are preferentially active against
specific viral genotypes or subtypes. These data argue for surveillance of HCV resistance and
mixed HCV infection among PWID to resolve residual concerns regarding their clinical and
public health significance.
Two systematic reviews assessing interferon-based therapy for PWID have demonstrated
responses comparable to randomised controlled trials excluding PWID. These data have
supported international recommendations for the management of HCV for PWID. However, there
are limited data on DAA therapy among recent PWID. As treatment is broadened to include more
marginalised individuals, many clinicians are reluctant to treat HCV among PWID with recent
injecting drug use with new DAA therapies. Major concerns include poor adherence/response,
increased risk behaviour and HCV reinfection.
A major concern is that ongoing injecting risk behaviours following DAA therapy in PWID will
lead to HCV reinfection, reversing the benefits of cure. Ongoing risk behaviours following
successful HCV therapy may lead to reinfection and compromised treatment outcomes. In a
systematic review and meta-analysis of HCV reinfection among PWID performed by the
investigators, the pooled estimate of re-infection was 2.2/100 p-yrs (95% CI, 0.9-6.1)
overall and 6.4/100 p-yrs (95% CI, 2.5-16.7) among individuals who reported injecting drug
use post-SVR. The one study of HCV reinfection post-therapy in prison performed to date was
small (n=74), retrospective, and did not assess the rate of HCV reinfection. Studies of
reinfection following HCV therapy are limited by small sample sizes, retrospective study
designs, incomplete follow-up, and a lack of sensitive methods to detect reinfection.
Further, there are no data on HCV reinfection among recent PWID treated with DAAs.
Although DAA therapy could limit HCV-related disease burden, as treatment is broadened to
include more marginalised individuals, many clinicians are reluctant to treat HCV among
recent PWID, given concerns about poor adherence (and lower response to therapy), increased
risk behaviours (due to the ease and high cure rates of DAA HCV therapy) and HCV reinfection
(thereby reversing cure). However, no data exist on the extent to which this should be a
concern. Given that DAA HCV therapy is highly expensive, we urgently need data on the
magnitude of risk for, and predictors of, HCV reinfection. It is also unclear whether PWID
treated in these two settings will vary in their response to DAA therapy and risk for
reinfection.
The investigators have an excellent track record of conducting high quality cohort studies
and clinical trials among PWID in the community and prison, with high participant retention
in follow-up. The investigators have developed a network of community-based clinical sites
providing HCV care in nine community-based drug treatment clinics, and many years of
collaborative clinical research in the prison sector. In SHARP the investigators will explore
the risk of HCV reinfection and treatment efficacy among recent PWID with chronic HCV and
recent injecting drug use in the community and in the prisons.
