How cost-effective is hepatitis C virus treatment for people who inject drugs?

Chronic hepatitis C virus (HCV) is an important cause of liver disease. In Australia and many developed countries, the majority of infections are among people who inject drugs (PWID). Harm reduction interventions such as opiate substitution therapy and needle and syringe programs can reduce HCV transmission1 but have been unable to reduce HCV prevalence to low levels, such as in Australia, where background prevalence among PWID remains high (∼50%).2

HCV antiviral treatment, therefore, could be an important strategy for reducing HCV prevalence and the burden of liver disease,3 and policy-makers should be reminded that treatment of HCV is cost-effective. It has been shown previously that HCV treatment with interferon (IFN) or pegylated interferon (PEG-IFN) and ribavirin (RBV) is cost-effective for non-injectors or people who are no longer at risk of reinfection in a variety of global settings.4 More recently, two economic evaluation established treatment with telaprevir or boceprevir in combination with PEG-IFN and RBV as cost-effective for all genotype 1 patients in Italy5 and for genotype 1 patients with advanced fibrosis in the US.6

In this issue, Visconti A et al. contribute to the evidence on the cost-effectiveness of HCV treatment for PWID in Australia.7 The authors compared treatment with PEG-IFN + RBV at different disease stages (mild fibrosis, moderate fibrosis, or compensated cirrhosis) to no treatment. Using a Markov cohort model, they simulate three different cohorts of patients: never injectors, current injectors, and former injectors. Current injectors have a fixed rate of reinfection independent of prevalence, and former injectors have a risk of relapse (and subsequent reinfection). Additionally, in the model, PWID were assigned higher baseline mortality rates (which is known to be the case from other studies), disease progression rates, and lower treatment completion rates as compared with non-injectors. They report that early treatment is more cost-effective than late treatment (at compensated cirrhosis) for all cohorts. Early treatment of never injectors resulted in an incremental cost-effectiveness ratio (ICER) of AUD$3985 per quality-adjusted life-year (QALY) gained compared with no treatment, with early treatment of former PWID yielding an ICER of AUD$5808 per QALY gained compared with no treatment, and early treatment of current PWID yielding an ICER of AUD $7941 per QALY gained. Hence, the early treatment ICERs fell well below the AUD$50 000 willingness-to-pay threshold for all groups.

The authors also explored the cost-effectiveness of treatment with new protease inhibitors (telaprevir and boceprevir in combination with PEG-IFN + RBV) compared with standard dual therapy (PEG-IFN + RBV), finding that treatment at the moderate fibrosis or compensated cirrhosis stages falls under the AUD$50 000 per QALY willingness-to-pay threshold for all groups. However, Visconti et al. find treatment of mild fibrosis cost-effective only for non-injectors, and not cost-effective for former or current injectors.

Visconti et al.7 corroborate other studies showing that HCV treatment with IFN or PEG-IFN and RBV for current or former PWID is cost-effective in the US, Europe, and New Zealand.8-16 This is crucially important as few injectors are treated for HCV,2, 17 and some clinicians discourage treatment of current PWID due to perceived risks of reinfection or non-completion/noncompliance. This is despite the available evidence indicting that reinfection rates following treatment are low18, 19 and sustained viral response (SVR) rates are similar among PWID as compared to non-injectors.20 However, these studies contained small sample sizes and were likely subject to considerable selection bias in participants. For instance, it is possible that the most stable or compliant PWID were chosen, so further work is needed to evaluate reinfection and SVR rates among the broader PWID population. Nevertheless, Visconti et al. have shown that treatment of PWID is cost-effective despite the inclusion of reinfection and lower compliance for current and former PWID,7 thus providing strong evidence supporting the scale-up of treatment to these groups.

However, the likely reason why Visconti et al. find that treating PWID is less cost-effective than treating ex- or non-injectors is because reinfection has been included but the prevention benefit of treating PWID has been ignored. Removing chronically infected PWID averts secondary infections that those PWID may have caused and also reduces HCV chronic prevalence in the population.3 Indeed, treating PWID may be more cost-effective than treating former or non-injectors because of the substantial benefits achieved through averting secondary infections, despite the risk of reinfection or lower SVR rates among PWID.8

The result of omitting these transmission dynamics is that Visconti et al.'s model might give a misleading picture. Based on their model, non-injectors and ex-injectors would be preferentially treated rather than PWID—whereas the reverse may have been found if the model had been dynamic and allowed for any potential prevention benefit. Additionally, their model indicates early treatment with protease inhibitors is only cost-effective for non-PWID; however, inclusion of the prevention benefit could make treatment of PWID cost-effective as well.

The HCV treatment landscape is rapidly changing. Within 3–5 years, it is likely that IFN-free direct-acting antiviral therapies will be available with very high SVR rates (> 90% for all genotypes), short durations (8–12 weeks), high barriers to resistance, low toxicity, and once- or twice-daily oral-only dosing.21-24 This could lead to dramatically higher uptake rates, particularly among PWID, especially if delivered in the community setting. Future work will need to examine the impact and cost-effectiveness of these IFN-free direct-acting antiviral treatments for PWID, incorporating the prevention benefits of treatment so as to fully account for the advantages as well as disadvantages of treating PWID. Additionally, future analyses will need to evaluate the affordability of scaling up these new treatments to PWID for the purposes of reducing HCV transmission to very low levels, given the large numbers of people who need to be treated and the high cost of current treatments.