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 licenced 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.”
Martin NK et al. HCV treatment for prevention among people who inject drugs: modeling treatment scale-up in an age of direct-acting antivirals. Hepatology, online edition, Mar 28 (doi: 10.1002/hep.26431), 2013.