Monday, July 11, 2016

Vaccination could have important role in control of UK HCV epidemic among people who inject drugs

A vaccine, even with low efficacy, could lead to meaningful reductions in the incidence and prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID), a modelling study published in PLOS One shows. 

An international team of investigators analysed the potential impact of three different vaccination scenarios – low, moderate and high efficacy – on the HCV epidemic among PWID in the UK over 20 and 40 years. A low efficacy vaccine (50% protection for five years) would halve prevalence over 20 years if large numbers of PWID were vaccinated each year. Vaccination rates needed to reduce incidence were lower than those required for falls in prevalence, regardless of the potency of the vaccine.

Researchers also compared the impact of vaccination with HCV treatment on the UK epidemic, calculating the number of vaccinations needed per case of treatment with new direct-acting antivirals (DAAs) to achieve the same effect.

“Our analysis suggests that even low efficacy HCV vaccines could have considerable impact; potentially halving HCV prevalence and incidence among PWID in 40 years for vaccine coverage levels comparable to what has been achieved for HBV [hepatitis B virus] among PWID in the UK, 72% in 2013,” comment the investigators. “Our modelling suggests that similar reductions in HCV prevalence or incidence could be achieved with 4-16 or 2-11 times fewer treatments. Nonetheless, at current HCV drug costs and even reduced costs, these ratios suggest that vaccination could be a much cheaper strategy for reducing HCV transmission than scaling up-treatment.”

Globally, 60% of PWID have antibodies to HCV. This population is therefore a priority for HCV prevention efforts.

Research has suggested that therapy with new highly effective anti-HCV DAAs could have a significant impact on new infections among high-risk populations. However, these treatments are very expensive.

Vaccination could be an alternative prevention strategy and a partially effective vaccine could be available soon.

Investigators therefore wanted to assess the potential usefulness of a vaccine for HCV prevention and to compare its impact against new HCV therapies.

They therefore designed a model to determine the annual vaccination rates required to reduce chronic HCV prevalence and incidence among PWID by 25%, 50% and 75% over 20 and 40 years.

A treatment model was also developed to determine the corresponding annual treatment rates needed to achieve a similar impact. The investigators also calculated vaccination-to-treatment ratio, i.e. the number of vaccinations needed per treatment to achieve the same result.

The vaccination model considered the potential impact of three scenarios:

    A low efficacy vaccine – 50% protection for five years
    A medium efficacy vaccine – 70% protection for ten years
    A high efficacy vaccine – 90% protection for 20 years.

The baseline scenario of the model was the current 40% prevalence of chronic HCV among PWID in the UK.

Annual vaccination rates of 100 per 1000 PWID could achieve reductions in prevalence of 35%, 65% or 85% after 40 years for low, medium and high efficacy vaccines, respectively. A vaccination rate below 50 per 1000 PWID would have only a modest impact (20% reduction in 50 years) for a low efficacy vaccine, but could halve prevalence within 30 years with use of a high efficacy vaccine.

A low efficacy vaccine would not halve prevalence over 20 years, but this result could be achieved over 40 years with high vaccination rates (162 per 1000 PWID). Higher efficacy vaccines required much lower annual vaccination rates to achieve this outcome.

Moderate and high efficacy vaccines could achieve 75% reduction over 40 years with annual vaccination rates of 138 and 79 per 1000 PWID, respectively.

The required vaccination levels needed to reduce HCV incidence over both 20 and 40 years was smaller than that required to reduce prevalence. A moderately potent vaccine required rates of 64 and 129 per 1000 PWID to halve incidence and prevalence, respectively, over 20 years.

Comparison of the impact of vaccination to treatment revealed that the vaccination rate needed to achieve a 25% reduction in prevalence over 40 years was 3.4, 6 or 13 times greater, depending on vaccine efficacy, than the treatment rate needed for the same impact. These ratios increased for greater reductions in prevalence. But the vaccination-to-treatment ratio was much lower when the impact on incidence was considered. Only five vaccinations per treatment were needed to halve incidence over 40 years for a moderately effective vaccine. Despite this, in all scenarios considered, ratios favoured treatment, with the lowest ratio (1.9) seen when considering the vaccination rate needed to reduce incidence by 25% over 20 years with a high efficacy product.

Further analysis showed that the benefits of vaccination compared to treatment improved in PWID populations with shorter duration of injecting or higher HCV prevalence.

“It is useful to understand when the benefits of vaccination are heightened,” write the authors. “HCV vaccination compares better to treatment for reducing HCV incidence than reducing HCV prevalence, and when targeting higher-risk PWID. This suggests that vaccination could be preferable to treatment in high prevalence settings or among high-risk PWID subgroups, when treatment alone may not be suitable because of the considerable risk of re-infection.”

The results of the study are consistent with other research that modelled the potential impact of a vaccine on the dynamics of the HCV epidemic among PWID in San Francisco.

The authors note that the infrastructure for HCV vaccination is in place in the UK because of HBV immunisation campaigns and that high-levels of HBV vaccination coverage have been achieved among PWID in some UK settings. An attraction of HCV vaccination would be its likely cost, which could be approximately $500 per PWID, at least 50 times less than the current cost of HCV DAA therapy in high-income settings.

“It is possible that treatment and vaccination could act in unison,” conclude the authors, “with HCV uninfected PWID receiving vaccination and HCV infected PWID receiving treatment, and possibly then vaccination.”

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