Current and emerging antiviral treatments for hepatitis C infection
Direct-acting anti-viral (DAAs) therapies have changed the hepatitis C landscape. Previously, only small numbers of people with hepatitis C infection underwent treatment, even in countries with highly developed health systems. Now, due to DAAs’ high efficacy, low side-effect profile and relatively short treatment duration , concepts such as ‘treatment as prevention’ and ‘cure and prevention’ and hepatitis C elimination are being discussed [2-4]. Achieving hepatitis C elimination will require a significant increase in the number of people being treated for hepatitis C. Rather than ‘can we cure?’, the question is now ‘who should we cure first?’. This question is driven partly by the prohibitively high cost of DAA treatment . If DAAs were cheap, then anyone who wanted treatment would be given treatment—but that is not the current reality. Instead, the high cost of DAAs is driving discussion about whether treatment should, at least initially, be restricted to people with severe hepatitis fibrosis to reduce the risk of hepatocellular carcinoma, liver failure and death to keep costs in check.
“Models suggest that, depending on the initial population prevalence, treating as few as 15 of 1000 PWID per year can halve the prevalence of hepatitis C in 15 years.”
Many argue that despite the initial costs we should also treat people who engage in behaviours that lead to hepatitis C transmission, such as people who inject drugs (PWID), the group at greatest risk of hepatitis C infection in developed countries, because of a broader community benefit and probable long-term cost-effectiveness. Models suggest that, depending on the initial population prevalence, treating as few as 15 of 1000 PWID per year can halve the prevalence of hepatitis C in 15 years .
As highlighted in the paper by de Vos et al., the impact of treatment on reducing hepatitis C virus (HCV) prevalence in the population can be enhanced by targeting HCV treatment by risk level .
Similarly, modelling by the Burnet Institute in Melbourne, Australia suggests that targeting the injecting network delivers greater population health benefit than treating PWID randomly for their hepatitis C . It is postulated that these ‘treatment as prevention’ approaches can lead to hepatitis C elimination in 15–20 years.
The answer to the question of who to cure ‘first’ may also be driven, in part, by the stigma and discrimination associated with injecting drugs [9, 10]. In the recent pegylated interferon (PEG-IFN) and ribavirin era, many PWID were not offered hepatitis C treatment due to concerns about compliance and poor treatment response. However, the evidence suggests that PWIDs’ compliance and treatment outcomes were no different to those of other groups [4, 11].
Risk; Ours or Theirs?
In the DAA era, there is a view that PWID should not be treated because of their high risk of hepatitis re-infection. While hepatitis C re-infection in PWID is quite common outside the treatment setting [12, 13], re-infection post-treatment with PEG-IFN and ribavirin is considerably lower, estimated by one meta-analysis of five studies at 2.4 [95% confidence interval (CI) = 0.9–6.1] per 100 person-years . Despite this, many of the current models measuring the impact of treatment on HCV prevalence (including de Vos et al. and the authors of this commentary) build high levels of re-infection into their model’s assumptions, perpetuating this probable overstatement of re-infection risk. That treatment appears to lower future risk suggests that injecting risk categories may be temporal, and models that incorporate risk levels that change throughout the course of an injecting career should be considered instead.
This makes allocating treatments by risk status a less well-defined approach, and the resources required to do so may not be worth the marginal benefits that modelling suggests could be gained . Hence, PWID should not be excluded from treatment based simply on their risk behaviour at one moment in time.Also, there is no reason to expect that PWID treated with DAAs are more likely to become re-infected than PWIDs treated with the PEG-IFN and ribavirin in the past.
“The view—which has been expressed publicly at large international meetings—that current treatment is ‘easy’, and consequently PWID will not fear re-infection and re-treatment, is simply not evidence-based.”
The view—which has been expressed publicly at large international meetings—that current treatment is ‘easy’, and consequently PWID will not fear re-infection and re-treatment, is simply not evidence-based.While models and empirical evidence are important tools in our efforts to convince policymakers of the cost-effectiveness and broader public health benefit of increasing access to hepatitis C treatment, it is vitally important to recall that we are talking about individuals infected with a chronic blood-borne virus.
The stigma associated with hepatitis C warps judgements about treatment allocation. It is difficult to think of another potentially fatal disease for which we would not make the >90% effective cure widely available. For example, people with hypertension and raised cholesterol are treated routinely to stop them developing cardiac disease. Similarly, it is difficult to think of another disease for which we refuse to provide treatment for fear that the sufferer may require further treatment in the future; cardiac disease, often related to behaviours such as poor diet and lack of exercise, again comes to mind.
“Similarly, it is difficult to think of another disease for which we refuse to provide treatment for fear that the sufferer may require further treatment in the future;”
In the arguments to come about the cost and cost-effectiveness of hepatitis C treatment and who should be treated ‘first’, it is important to keep in mind that a cure for hepatitis C changes the landscape. Adequate health care is a basic human right; providing the existing cure for hepatitis C to all—when they want treatment, regardless of how they became infected—is our responsibility.
Thanks to the authors and to British Journal of Clinical Pharmacology for the reprinting of this article.
Note: INPUD gets involved with supporting more affordable access to Hepatitis C drugs by joining with other global HIV/AIDS organisations and writing to UNITAIDS. The response has been seen as an ‘advocacy win’ and a tiny step forward in the long and comp!ex road ahead. Letters posted here over the next days.
Also, stay tuned for blogging about the roots of the European Network of People who Use Drugs to be decisively planted next week in London.