New combinations of hepatitis C drugs could
have major public health benefits, a modelling study published in the online
edition of Hepatology shows.
Scaling-up treatment rates in Edinburgh,
Melbourne and Vancouver has the potential to achieve significant reductions in
prevalence of hepatitis C virus (HCV) among injecting drug users, the model
shows. Doubling current treatment rates would reduce HCV prevalence among
injecting drug users in Edinburgh by 50%, but a similar reduction in prevalence
in Melbourne and Vancouver would require 13- and 15-fold increases in treatment
rates.
Professor David Goldberg, who lead the team
implementing Scotland’s Hepatitis C Action plan between 2008 and 2011, was
encouraged by the findings of the research: “This study demonstrates that, in a
country like Scotland which has a government seriously committed to the
improvement of hepatitis C services, increasing patient access to antiviral
therapy could potentially have a major impact in the prevention of transmission
of infection.”
Approximately 150 million people globally
are infected with HCV. Some 60% of existing and 80% of new HCV infections
involve injecting drug users.
Harm reduction is at the core of current
HCV prevention initiatives targeted at people who inject drugs. However, needle
and syringe exchange programmes and opiate substitution therapy have had only a
limited impact on incidence rates.
Current treatment for HCV is based upon
pegylated interferon and ribavirin. This treatment can result in clearance of
the infection in up to 60% of people. However, uptake rates among injecting
drug users are low, possibly because of the long duration of therapy (up to 48
weeks) and high risk of side-effects.
A number of promising oral drugs that work
directly against HCV are in clinical trials. Preliminary results suggest that
treatment with combinations of direct-acting agents (DAAs) can achieve response
rates above 90% and that the drugs have a much milder side-effect profile than
current therapies.
Antiretroviral therapy for HIV infection
has been shown to reduce the risk of onward transmission of the virus by up to
96%, and the use of HIV treatment as prevention is currently the focus of
intensive research.
Investigators wished to assess the
potential role in prevention of combinations of new HCV DAAs.
They developed a mathematical model for
three cities – Edinburgh, Melbourne and Vancouver – each of which has a
similar prevalence of injecting drug users in the adult population (below 1%). Prevalence
of chronic HCV infection among people who inject drugs in the three cities
varies markedly, from 25% in Edinburgh, to 50% in Melbourne and 65% in Vancouver.
The model assumed that therapy with DAAs
lasting twelve weeks would achieve a sustained virological response in over 90%
of people. The authors calculated treatment rates needed to reduce prevalence
of chronic HCV infection among injecting drug users by 50 and 75% over 15
years.
The current treatment rate among
chronically infected injecting drug users in Edinburgh is 3%. The model showed
that, if uptake of DAA treatment remained at this level, the prevalence of
chronic HCV among the city’s injecting population would be reduced by 26% by
2017.
In both Melbourne and Vancouver, the
treatment uptake rate is only 1% each year. The investigators showed that at
this level of uptake, therapy with DAAs would only achieve a 2% reduction in
prevalence over 15 years.
To achieve a 50% reduction in prevalence by
2015, the proportion of individuals treated with DAAs each year in Edinburgh would
need to double. A similar reduction in Melbourne and Vancouver would require
treatment rates with DAAs to increase 13- and 15-fold respectively.
A 75% reduction in prevalence would require
a three-fold increase in treatment rates in Edinburgh, an 18-fold increase in
Melbourne and a 20-fold increase in Vancouver.
“This would result in chronic HCV
prevalences of <10% in Edinburgh, <15% in Melbourne and 20% in
Vancouver,” note the authors.
“The development of highly effective
simplified new HCV treatments has the potential to greatly enhance existing HCV
prevention strategies,” said Professor Greg Dore of the University of New South
Wales. “Access to affordable HCV direct acting antiviral regimens for people
who inject drugs should be a major focus to harness this potential prevention
capacity.”
The rapid expansion of access to HIV
therapy could provide a model for the scaling up of HCV therapy. However, as
with antiretroviral treatment, cost is likely to be an issue. Assuming that the
cost of new DAAs would be similar to the already licensed HCV protease
inhibitors, then the annual cost of treatment in Edinburgh would be US$3.2
million and the approximate annual costs in Melbourne and Vancouver would be in
the region of $50 million.
“HCV treatment is cost-effective,” conclude
the authors. “In most settings treatment of people who inject drugs is highly
cost-effective primarily because of the potential prevention benefit and
reduction in secondary transmission.”