Can Direct-Acting Antivirals Finally Achieve Hepatitis C Elimination?

The World Health Organization target is to eliminate viral hepatitis as a public health threat, with a target of 90% reduction in incidence and a 65% reduction in mortality by 2030.¹ A major tool to achieve these aims is the treatment and cure of hepatitis C (HCV) with direct-acting antiviral (DAA) medications. Modelling studies have indicated the potential for successful treatment to have an impact on incidence. However, a real-life reduction in new transmissions following widespread implementation of treatment has not previously been demonstrated.

Two reports published in Clinical Infectious Diseases demonstrated impressive evidence for the transformative benefit of HCV treatment with DAAs.^2,3 In The Netherlands, unrestricted access to DAAs was provided to the whole population in November 2015. Following this provision, high uptake has been found in the HIV/HCV co-infected population.

Boerekamps and colleagues reported on data obtained from the ATHENA HIV observational cohort, which registers >98% of people living with HIV (PLWH) in The Netherlands.² Of 1471 HCV/HIV co-infected individuals in the country, 87% (1284 of 1471) initiated HCV treatment between 2000 and 2017. Sustained virologic cure was achieved in 76% of patients (1124 of 1471), with a further 6% awaiting results from DAA treatment.  

The HIV risk factors for this group were 69% for men who have sex with men (MSM), 15% people who inject drugs (PWID) and 15% with another route of transmission. The highest sustained viral response rate was 83% in those with MSM as risk factor which was significantly higher than in the overall population (P >.001). There were 14 DAA failures and 54 patients in whom therapy with a pegylated-alfa interferon-based regimen failed.

A second report compared the incidence of acute HCV infection before and after the introduction of unrestricted DAAs.³ In 2014, 93 acute HCV infections were diagnosed during 8290 person-years of follow up and by 2016, 49 acute HCV infections were diagnosed during 8961 person-years of follow up. The incidence risk ratio was 0.49 (95% CI, 0.35-0.69) comparing the two periods. This is equivalent to a 51% reduction in acute HCV infections among HIV-positive MSM. The authors also noted a significant increase in the rate of syphilis (from 6.6% to 8.4%; P =.001) and gonorrhoea (from 16.4% to 19.2%; P =.001) in the same HIV-positive MSM population over the same time period.

Infectious Disease Advisor spoke with Jürgen Kurt Rockstroh, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn in Germany, and author of a commentary on the 2 studies outlined above,⁴ and Bart Rijinders, of the Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands, to comment on the significance of these study findings.

Infectious Disease Advisor: A recent study shows an impressive drop in the incidence of acute HCV infections following widespread treatment and cure of HIV/HCV co-infected individuals. Do you think this reduction is likely to continue in the Netherlands as more people are successfully treated or will we see a plateau?

Dr Rockstroh: As there still were roughly 25% left untreated, the hope is that as roll-out of DAA therapy continues, a further decline can be achieved. It looks as though some patient groups are more difficult to reach and so HCV microelimination may face some challenges.

Also, reinfections may occur not only within the country but also abroad in risk situations and countries where DAA access is different. The Swiss HCV elimination study has shown very similar results, which is clearly a further encouraging signal.

Infectious Disease Advisor: How robust is the treatment as prevention effect and can it be applied to other populations of people living with or at risk for HCV infection?

Dr Rockstroh: I think the treatment as prevention effect has now been shown to work well for the HIV-coinfected MSM patient group, which is at the highest risk for reinfection. Infections from outside the country but also reinfections through less well identified HIV-negative MSM with HCV infection remain a challenge.

For the PWID risk group, reinfection rates can also be well controlled if harm reduction efforts are maintained. So here it really depends more on good access to clean syringes and needles as well as access to substitution programs. This unfortunately cannot be guaranteed everywhere (the prison setting is a particularly big challenge).

Patients with HCV from blood products are at low risk for reinfection and treatment as prevention will not play a big role here.

Infectious Disease Advisor: Is unrestricted access to DAAs alone likely achieve elimination of HCV in HCV/HIV co-infected individuals in The Netherlands?

Dr Rijinders: We discuss other interventions that we think will need to be done in our paper published in the Journal of the International AIDS Society.⁵ We focused on HIV-negative MSM (in particular pre-exposure prophylaxis users) and examined the high risk for HCV reinfection and cross-border transmission (because DAA uptake is less pronounced in some neighboring countries). We are planning several of these interventions at sexually transmitted infection clinics.

Infectious Disease Advisor: Is this generalizable to other populations?

Dr Rijinders: It will only be generalizable to other populations that are easy to reach to have the HCV diagnosed and treated. So, this could apply to methadone or other opioid substitution users or PWID but only if other preventive interventions like effective needle exchange programs are also in place.

Infectious Disease Advisor: Are there any data for a further fall in acute HCV incidence since publication?

Dr Rijinders: We actually have (unpublished) data from 2017 showing that it has not declined further. 

Conclusion

Unrestricted use of DAAs may be an invaluable component of preventing HCV transmission by reducing the infectious pool of individuals. Reaching elimination targets will, however, require a range of additional approaches including scale-up of diagnostic services to target hard to identify groups and harm reduction programs in PWID.

References

1. World Health Organization. Combating hepatitis B and C to reach elimination by 2030. Published May 2016. Accessed July 3, 2018.
2. Boerekamps A, Newsum AM, Smit C, et al. High treatment uptake in human immunodeficiency virus/hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands. Clin Infect Dis. 2018;66(9):1352-1359.
3. Boerekamps A, Van den Berk GE, Lauw FN, et al. Declining hepatitis C virus (HCV) incidence in Dutch human immunodeficiency virus-positive men who have sex with men after unrestricted access to HCV therapy. Clin Infect Dis. 2018;66(9):1360-1365.
4. Rockstroh JK. Is Hepatitis C virus elimination in well-defined patient groups possible? Clin Infect Dis. 2018;66(9):1366-1367.
5. Martin NK, Boerekamps A, Hill AM, Rijnders BJA. Is hepatitis C virus elimination possible among people living with HIV and what will it take to achieve it? J Int AIDS Soc. 2018,21(S2):e25062.