Purpose of review

The burden of hepatitis C virus (HCV) is high among people who inject drugs (PWID) and prisoners, and increasing among HIV-infected MSM, who are key populations for HCV transmission in high-income countries and may also play a role in many in low- and middle-income countries. There is an increasing interest in the use of HCV antiviral treatment for prevention in these populations.

Recent findings

Numerous theoretical modelling studies have explored the potential impact of HCV treatment for prevention among PWID in a range of global settings, generally finding that modest and achievable levels of HCV treatment, especially with interferon-free direct-acting antiviral therapy (IFN-free DAAs), could substantially reduce HCV chronic prevalence among PWID within the next 10-20 years. In addition, modelling studies have shown HCV testing and treatment in prison (including prevention benefits) could be cost-effective if continuity of care is ensured, or HCV treatments are shortened with DAAs. Modelling work among HIV-infected MSM has shown that further HCV treatment scale-up is likely required despite high treatment rates in this population. However, no empirical studies have explored whether HCV treatment can reduce HCV prevalence and prevent onwards transmission among those at risk of transmission.

Summary

HCV treatment for key populations such as PWID, prisoners and MSM could become an important HCV prevention intervention, especially in the IFN-free DAA era. However, there is an urgent need to test these hypotheses through empirical studies.

People who inject drugs (PWID) are at high risk for acquiring hepatitis C virus (HCV), but many are unaware of their infection. HCV dried blood spot (DBS) testing increases case-finding in addiction services and prisons. We determine the cost-effectiveness of increasing HCV case-finding among PWID by offering DBS testing in specialist addiction services or prisons as compared to using venepuncture. Cost-utility analysis using a dynamic HCV transmission model among PWID, including: disease progression, diagnosis, treatment, injecting status, incarceration and addition services contact. DBS testing in specialist addiction services or prisons. Intervention impact was determined by a meta-analysis of primary data. Costs (in UK £, £1=US$1.60) and utilities (quality-adjusted life years, QALYs) were attached to each state and the incremental cost effectiveness ratio (ICER) determined. Multivariate uncertainty and one-way sensitivity analyses were performed. For a £20 000 per QALY gained willingness-to-pay threshold, DBS testing in addiction services is cost-effective (ICER of £14 600 per QALY gained). Under the base-case assumption of no continuity of treatment/care when exiting/entering prison, DBS testing in prisons is not cost-effective (ICER of £59 400 per QALY gained). Results are robust to changes in HCV prevalence; increasing PWID treatment rates to those for ex-PWID considerably reduces ICER (£4500 and £30 000 per QALY gained for addiction services and prison, respectively). If continuity of care is >40%, the prison DBS ICER falls below £20 000 per QALY gained. Despite low PWID treatment rates, increasing case-finding can be cost-effective in specialist addiction services, and in prisons if continuity of treatment/care is ensured.

Purpose of review

The majority of hepatitis C virus (HCV) infections in the United Kingdom and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk - such as people who inject drugs (PWID) - irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID.

Recent findings

There is good theoretical evidence from dynamic models that HCV treatment for PWID could reduce HCV chronic prevalence and incidence among PWID. Economic evaluations from high-income settings have suggested HCV treatment for PWID is cost-effective, and that in many settings HCV treatment of PWID could be more cost-effective than treating those at an equivalent stage with no ongoing transmission risk. Epidemiological studies of older interferon treatments have suggested that PWID can achieve similar treatment outcomes to other patient groups treated for chronic HCV. Impact and cost-effectiveness of HCV treatment is driven by the potential 'prevention benefit' of treating PWID. Model projections suggest that more future infections, end stage liver disease, and HCV-related deaths will be averted than lost through reinfection of PWID treated successfully for HCV. However, there is to date no empirical evidence from trials or observational studies that test the model projections and 'prevention benefit' hypothesis. In part this is because of uncertainty in the evidence base but also there is unlikely to have been a change in HCV prevalence due to HCV treatment because PWID HCV treatment rates historically in most sites have been low, and any scale-up and switch to the new direct acting antiviral has not yet occurred. There are a number of key uncertainties in the data available on PWID that need to be improved and addressed to evaluate treatment as prevention. These include estimates of the prevalence of PWID, measurements of HCV chronic prevalence and incidence among PWID, and how to interpret reinfection rates as potential outcome measures.

Summary

Eliminating HCV through scaling up treatment is a theoretical possibility. But empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.

Background

HCV incidence is increasing in the US, notably among younger people who inject drugs (PWID). In a cohort of young adult (age<30 years) PWID in San Francisco we examined whether 'injecting partner mixing' factors, i.e. age of partner and knowledge of their HCV serostatus, were associated with HCV transmission.

Methods

In 448 susceptible PWID studied prospectively. All participants were asked to report characteristics and behaviors they engaged in with up to 3 injecting partners defined as "people whom you injected the most with" in the past month". These partnerships did not specify that drugs or injecting equipment was shared. HCV incidence was estimated by age of up to 3 injecting partners, categorized as: (i) all <30; (ii) mixed-age (<&≥30); and (iii) all ≥30 years and perceived knowledge of the HCV status of participants' injecting partners' HCV status. Interaction was evaluated between partnership age categories and perceived HCV status of partners.

Results

Between 2006-2018, overall HCV incidence (/100 person years observation [pyo]) was 19.4 (95% CI: 16.4, 22.9). Incidence was highest in those with mixed-age partnerships: 28.5 (95% CI: 21.8, 37.1) and those whose partners were all <30 (23.9; 95% CI: 18.8, 30.4), and lowest if partners were ≥30 (7.5; 95% CI: 4.8, 11.8). In a multivariable analyses adjusting for age, sex (of index), injection frequency, and injection partnership 'monogamy', we found evidence for an interaction: the highest HCV incidence was seen in PWID whose partners were all <30 and who knew at least one of their partners was HCV-positive (58.9, 95% CI: 43.3, 80.0; p<0.01).

Conclusions

Younger injectors are more likely to acquire HCV from their similarly-aged peers, than older injecting partners. Protective seroadaptive behavior may contribute to reduce incidence. These findings can inform new HCV prevention approaches for young PWID needed to curb the HCV epidemic.

Background

Hepatitis C virus (HCV) elimination is being seriously considered globally. Current elimination models require a combination of highly effective HCV treatment and harm reduction, but high treatment costs make such strategies prohibitively expensive. Vaccines should play a key role in elimination but their best use alongside treatments is unclear. For three vaccines with different efficacies we used a mathematical model to estimate the additional reduction in HCV prevalence when vaccinating after treatment; and to identify in which settings vaccines could most effectively reduce the number of treatments required to achieve fixed reductions in HCV prevalence among people who inject drugs (PWID).

Methods

A deterministic model of HCV transmission among PWID was calibrated for settings with 25, 50 and 75% chronic HCV prevalence among PWID, stratified by high-risk or low-risk PWID. For vaccines with 30, 60 or 90% efficacies, different rates of treatment and vaccination were introduced. We compared prevalence reductions achieved by vaccinating after treatment to prevent reinfection and vaccinating independently of treatment history in the community; and by allocating treatments and vaccinations to specific risk groups and proportionally across risk groups.

Results

Vaccinating after treatment was minimally different to vaccinating independently of treatment history, and allocating treatments and vaccinations to specific risk groups was minimally different to allocating them proportionally across risk groups. Vaccines with 30 or 60% efficacy provided greater additional prevalence reduction per vaccination in a setting with 75% chronic HCV prevalence among PWID than a 90% efficacious vaccine in settings with 25 or 50% chronic HCV prevalence among PWID.

Conclusions

Vaccinating after treatment is an effective and practical method of administration. In settings with high chronic HCV prevalence among PWID, even modest coverage with a low-efficacy vaccine could provide significant additional prevalence reduction beyond treatment alone, and would likely reduce the cost of achieving prevalence reduction targets.

Background

Interventions such as opiate substitution therapy (OST) and high-coverage needle and syringe programs (HCNSP) cannot substantially reduce hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV antiviral treatment may prevent onward transmission. We project the impact of combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among PWID.

Methods

An HCV transmission model among PWID was used to project the combinations of OST, HCNSP, and antiviral treatment required to achieve different prevalence and incidence reductions within 10 years for 3 chronic prevalence scenarios and the impact of HCV treatment if only delivered through OST programs. Multivariate and univariate sensitivity analyses were performed.

Results

Large reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral treatment. Scaling up OST and HCNSP substantially reduces the treatment rate required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage were increased to 40% each (no coverage at baseline), then annually treating 10, 23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60% baseline chronic HCV prevalences, respectively. Approximately 30% fewer treatments are necessary with new direct-acting antivirals. If coverage of OST and HCNSP is 50% at baseline, similar prevalence reductions require higher treatment rates for the same OST and HCNSP coverage.

Conclusions

Combining antiviral treatment with OST with HCNSP is critical for achieving substantial reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are required on how best to scale up antiviral treatment and combine treatment with other interventions.

It’s difficult to develop infectious disease interventions (such as for HIV) for overlapping high-risk populations such as people who inject drugs, men who have sex with men, and female sex workers, where there are multiple transmission routes. Recent advances in dynamic modelling of coinfection epidemics could disentangle the contributions of different risk groups and behaviours to help develop more efficient and effective prevention interventions.

Background and objectives

Promoted globally as an evidence-based intervention in the prevention of HIV and treatment of heroin addiction among people who inject drugs (PWID), opioid substitution treatment (OST) can help control emerging HIV epidemics among PWID. With implementation in December 2014, Kenya is the third Sub-Saharan African country to have introduced OST. We combine dynamic mathematical modelling with qualitative sociological research to examine the 'promise of methadone' to Kenya.

Methods, setting and participants

We model the HIV prevention impact of OST in Nairobi, Kenya, at different levels of intervention coverage. We draw on thematic analyses of 109 qualitative interviews with PWID, and 43 with stakeholders, to chart their narratives of expectation in relation to the promise of methadone.

Results

The modelled impact of OST shows relatively slight reductions in HIV incidence (5-10%) and prevalence (2-4%) over 5 years at coverage levels (around 10%) anticipated in the planned roll-out of OST. However, there is a higher impact with increased coverage, with 40% coverage producing a 20% reduction in HIV incidence, even when accounting for relatively high sexual transmissions. Qualitative findings emphasise a culture of 'rationed expectation' in relation to access to care and a 'poverty of drug treatment opportunity'. In this context, the promise of methadone may be narrated as a symbol of hope-both for individuals and community-in relation to addiction recovery.

Conclusions

Methadone offers HIV prevention potential, but there is a need to better model the effects of sexual HIV transmission in mediating the impact of OST among PWID in settings characterised by a combination of generalised and concentrated epidemics. We find that individual and community narratives of methadone as hope for recovery coexist with policy narratives positioning methadone primarily in relation to HIV prevention. Our analyses show the value of mixed methods approaches to investigating newly-introduced interventions.

Background

HCV direct-acting antivirals (DAAs) are produced in India at low cost. However, concerns surrounding reinfection and budgetary impact limit treatment scale-up in India. We evaluate the cost-effectiveness and budgetary impact of HCV treatment in India, including reinfection.

Methods

A closed cohort Markov model of HCV disease progression, treatment, and reinfection was parameterized. We compared treatment by fibrosis stage (F2-F4 or F0-F4) to no treatment from a health care payer perspective. Costs (2017 USD$, based on India-specific data) and health utilities (in quality-adjusted life years, QALYs) were attached to each health state. We assumed DAAs with 90% sustained viral response at $900/treatment and 1%/year reinfection, varied in the sensitivity analysis from 0.1-15%. We deemed the intervention cost-effective if the incremental cost-effectiveness ratio (ICER) fell below India's per capita GDP ($1,709). We assessed the budgetary impact of treating all diagnosed individuals.

Results

HCV treatment for diagnosed F2-F4 individuals was cost-saving (net costs -$2,881 and net QALYs 3.18/person treated; negative ICER) compared to no treatment. HCV treatment remained cost-saving with reinfection rates of 15%/year. Treating all diagnosed individuals was likely cost-effective compared to delay until F2 (mean ICER $1,586/QALY gained, 67% of simulations falling under the $1,709 threshold) with 1%/year reinfection. For all scenarios, annual retesting for reinfection was more cost-effective than the current policy (one-time retest). Treating all diagnosed individuals and reinfections results in net costs of $445-1,334 million over 5 years (<0.25% of total health care expenditure over 5 years), and cost-savings within 14 years.

Conclusions

HCV treatment was highly cost-effective in India, despite reinfection. Annual retesting for reinfection was cost-effective, supporting a policy change towards more frequent retesting. A comprehensive HCV treatment scale-up plan is warranted in India.

Background and aims

The individual-level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established, but there is less evidence on population-level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in the community and prisons on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation.

Design

Dynamic modeling.

Setting and participants

A cohort of 49 359 individuals who ever received OAT in NSW from 2001 to 2018.

Measurements

Receipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1-9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata: (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1-12 months ago. The model incorporated elevated mortality post-release from prison and OAT impact on reducing mortality and incarceration.

Findings

Among the cohort, mortality was 0.9 per 100 person-years, OAT coverage and retention remained high (> 50%, 1.74 years/episode). During 2001-20, we estimate that OAT provision reduced overdose and other cause mortality among the cohort by 52.8% [95% credible interval (CrI) = 49.4-56.9%] and 26.6% (95% CrI =22.1-30.5%), respectively. We estimate 1.2 deaths averted and 9.7 life-years gained per 100 person-years on OAT. Prison OAT with post-release OAT-linkage accounted for 12.4% (95% CrI = 11.5-13.5%) of all deaths averted by the OAT program, primarily through preventing deaths in the first month post-release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% (95% CrI =  0.8-2.0%) and 3.0% (95% CrI = 2.1-5.3%) of deaths, respectively.

Conclusion

The community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population-level overdose and all-cause mortality in the past 20 years, partially due to high retention.