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Mathematical modeling of hepatitis c virus (HCV) prevention among people who inject drugs: A review of the literature and insights for elimination strategies.

ABSTRACT: In 2016, the World Health Organization issued global elimination targets for hepatitis C virus (HCV), including an 80% reduction in HCV incidence by 2030. The vast majority of new HCV infections occur among people who inject drugs (PWID), and as such elimination strategies require particular focus on this population. As governments urgently require guidance on how to achieve elimination among PWID, mathematical modeling can provide critical information on the level and targeting of intervention are required. In this paper we review the epidemic modeling literature on HCV transmission and prevention among PWID, highlight main differences in mathematical formulation, and discuss key insights provided by these models in terms of achieving WHO elimination targets among PWID. Overall, the vast majority of modeling studies utilized a deterministic compartmental susceptible-infected-susceptible structure, with select studies utilizing individual-based network transmission models. In general, these studies found that harm reduction alone is unlikely to achieve elimination targets among PWID. However, modeling indicates elimination is achievable in a wide variety of epidemic settings with harm reduction scale-up combined with modest levels of HCV treatment for PWID. Unfortunately, current levels of testing and treatment are generally insufficient to achieve elimination in most settings, and require further scale-up. Additionally, network-based treatment strategies as well as prison-based treatment and harm reduction provision could provide important additional population benefits. Overall, epidemic modeling has and continues to play a critical role in informing HCV elimination strategies worldwide.

SUBMITTER: Pitcher AB

PROVIDER: S-EPMC6522340 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Mathematical modeling of hepatitis c virus (HCV) prevention among people who inject drugs: A review of the literature and insights for elimination strategies.

Pitcher Ashley B AB Borquez Annick A Skaathun Britt B Martin Natasha K NK

Journal of theoretical biology 20181116

In 2016, the World Health Organization issued global elimination targets for hepatitis C virus (HCV), including an 80% reduction in HCV incidence by 2030. The vast majority of new HCV infections occur among people who inject drugs (PWID), and as such elimination strategies require particular focus on this population. As governments urgently require guidance on how to achieve elimination among PWID, mathematical modeling can provide critical information on the level and targeting of intervention ...[more]

PMID: 30452959

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Project description:Background and aimsIn Latin America, Mexico was first to launch a hepatitis C virus (HCV) elimination strategy, where people who inject drugs (PWID) are a main risk group for transmission. In Tijuana, HCV seroprevalence among PWID is > 90%, with minimal harm reduction (HR). We evaluated cost-effectiveness of strategies to achieve the incidence elimination target among PWID in Tijuana.MethodsModeling study using a dynamic, cost-effectiveness model of HCV transmission and progression among active and former PWID in Tijuana, to assess the cost-effectiveness of incidence elimination strategies from a health-care provider perspective. The model incorporated PWID transitions between HR stages (no HR, only opioid agonist therapy, only high coverage needle-syringe programs, both). Four strategies that could achieve the incidence target (80% reduction by 2030) were compared with the status quo (no intervention). The strategies incorporated the number of direct-acting anti-viral (DAA) treatments required with: (1) no HR scale-up, (2) HR scale-up from 2019 to 20% coverage among PWID, (3) HR to 40% coverage and (4) HR to 50% coverage. Costs (2019 US$) and health outcomes [disability-adjusted life years (DALYs)] were discounted 3% per year. Mean incremental cost-effectiveness ratios (ICER, $/DALY averted) were compared with one-time per capita gross domestic product (GDP) ($9698 in 2019) and purchasing power parity-adjusted per capita GDP ($4842-13 557) willingness-to-pay (WTP) thresholds.ResultsDAAs alone were the least costly elimination strategy [$173 million, 95% confidence interval (CI) = 126-238 million], but accrued fewer health benefits compared with strategies with HR. DAAs + 50% HR coverage among PWID averted the most DALYs but cost $265 million, 95% CI = 210-335 million). The optimal strategy was DAAs + 50% HR (ICER $6743/DALY averted compared to DAAs only) under the one-time per-capita GDP WTP ($9698).ConclusionsA combination of high-coverage harm reduction and hepatitis C virus treatment is the optimal cost-effective strategy to achieve the HCV incidence elimination goal in Mexico.

Project description:BACKGROUND:Elimination of hepatitis C virus (HCV) among people who inject drugs (PWID) is a costly investment, so strategies should not only focus on eliminating the disease, but also on preventing disease resurgence. The aims of this study are to compute the minimum necessary antiviral therapies to achieve elimination with and without the additional expansion of harm reduction (HR) programs and to examine the sustainability of HCV elimination after 2030 if treatment is discontinued. METHOD:We considered two types of epidemic (with low (30%) and high (50%) proportion of PWID who engage in sharing equipment (sharers)) within three baseline chronic HCV (CHC) prevalence settings (30%, 45% and 60%), assuming a baseline HR coverage of 40%. We define sustainable elimination strategies, those that could maintain eliminations results for a decade (2031-2040), in the absence of additional treatment. RESULTS:The model shows that the optimum elimination strategy is dependent on risk sharing behavior of the examined population. The necessary annual treatment coverage to achieve HCV elimination under 45% baseline CHC prevalence, without the simultaneous expansion of HR programs, ranges between 4.7-5.1%. Similarly, under 60% baseline CHC prevalence the needed treatment coverage varies from 9.0-10.5%. Increasing HR coverage from 40% to 75%, reduces the required treatment coverage by 6.5-9.8% and 11.0-15.0% under 45% or 60% CHC prevalence, respectively. In settings with ?45% baseline CHC prevalence, expanding HR to 75% could prevent the disease from rebounding after elimination, irrespective of the type of the epidemic. In high chronic HCV prevalence, counseling interventions to reduce sharing are also needed to maintain the HCV incident cases in low levels. CONCLUSIONS:Harm reduction strategies have a vital role in HCV elimination strategy, as they reduce the required number of treatments to eliminate HCV and they provide sustainability after the elimination. The above underlines that HCV elimination strategies should be built upon the existing HR services, and argue for HR expansion in countries without services.

Project description:BackgroundIn 2019, Mexico became the first Latin American country committed to hepatitis C virus (HCV) elimination, but the amount of intervention scale-up required is unclear. In Tijuana, HCV among people who inject drugs (PWID) is high; yet there is minimal and intermittent harm reduction, and involuntary exposure to compulsory abstinence programs (CAP) occurs which is associated with increased HCV risk. We determined what combination intervention scale-up can achieve HCV elimination among current and former PWID in Tijuana.MethodsWe constructed a dynamic, deterministic model of HCV transmission, disease progression, and harm reduction among current and former PWID parameterized to Tijuana (~10,000 current PWID, 90% HCV seropositive, minimal opiate agonist therapy [OAT] or high coverage needle/syringe programs [HCNSP]). We evaluated the number of direct-acting antiviral (DAA) treatments needed from 2019 to achieve elimination targets (80% incidence reduction, 65% mortality reduction by 2030) with: (a) DAAs alone, (b) DAAs plus scale-up of OAT+HCNSP (up to 50% coverage of OAT and HCNSP separately, producing 25% of PWID receiving both), (c) DAAs plus CAP scale-up to 50%. Scenarios examined the number of DAAs required if prioritized to current PWID or provided regardless of current injection status, and impact of harm reduction interruptions.ResultsModeling suggests among ~30,000 current and former PWID in Tijuana, 16,160 (95%CI: 12,770-21,610) have chronic HCV. DAA scale-up can achieve the incidence target, requiring 770 treatments/year (95%CI: 640-970) if prioritized to current PWID. 40% fewer DAAs are required with OAT+HCNSP scale-up to 50% among PWID, whereas more are required with involuntary CAP scale-up. Both targets can only be achieved through treating both current and former PWID (1,710 treatments/year), and impact is reduced with harm reduction interruptions.ConclusionsElimination targets are achievable in Tijuana through scale-up of harm reduction and DAA therapy, whereas involuntary CAP and harm reduction interruptions hamper elimination.

Project description:ImportanceThe success of direct-acting antiviral therapies for chronic hepatitis C virus (HCV) infection led the World Health Organization to set elimination targets by 2030. For the United States to achieve these benchmarks, public health responses must target high-risk populations, such as people who inject drugs (PWID), a group with high rates of HCV incidence and low rates of treatment uptake.ObjectiveTo evaluate potential improvements in the HCV care cascade among PWID, focusing on improved testing, treatment uptake, and access to harm reduction.Design, setting, and participantsThis decision analytic model used a differential equation-based dynamic transmission model based on data from New Hampshire, an illustrative state with a large number of PWID and limited HCV treatment infrastructure. Surveillance data through 2020 was used for model parameterization, and the final analysis was conducted in May 2021.Main outcomes and measuresModel forecasts of chronic HCV cases and advanced-stage HCV outcomes from 2022 to 2045.ResultsA total of 6 scenarios were tested: (1) the base case, (2) improved harm reduction, (3) improved testing, (4) improved treatment, (5) improved testing and treatment, and (6) improved testing, treatment, and harm reduction. All scenarios with improved testing, treatment uptake, and/or access to harm reduction were associated with decreases in forecasted HCV prevalence and HCV-associated mortality compared with the base case. Improving harm reduction, testing, and treatment individually were forecast to reduce prevalence of HCV in 2045 from 69.7% in the base case to 62.8%, 45.7%, and 35.5%, respectively. Combining treatment and testing improvements was associated with a 2045 prevalence of 0.3%; adding harm reduction improvements was associated with further reductions in prevalence forecasts (to 0.2%), with fewer total treatments (10 960 vs 13 219 from 2022-2045).Conclusions and relevanceIn this modeling study, no single intervention was projected to achieve World Health Organization HCV elimination targets. Scenarios with improvements in both testing and treatment were associated with a prevalence of less than 3% by 2030 and achieved elimination targets. Adding improvements in harm reduction was associated with faster reductions in prevalence and fewer treatments.

Project description:Little is known about the distribution of hepatitis C virus (HCV) genotypes among people who inject drugs (PWID) in North African countries, including Tunisia. This study aims to describe HCV genotypes circulating among Tunisian PWID. A cross-sectional study was conducted, and 128 HCV-positive PWID were recruited between 2018 and 2019 from community-based harm reduction centers. After informed consent, sociodemographic characteristics and risk behavior data were obtained using an interviewer-administrated questionnaire. Blood samples were collected for further serological and molecular testing. Overall, five women and 123 men were included. The median age was 39.5 years. The majority of PWID (56.3%) had less than a secondary level of education, were single (57%), were unemployed (65.6%), were incarcerated at least once (93.0%), and had a history of residency in at least one foreign country (50.8%). During the previous 12 months, 82.0% reported having reused syringes at least once, 43.8% shared syringes at least once, while 56.2% had at least one unprotected sexual relation, and 28.1% had more than two different sexual partners. Tattooing was reported among 60.2%. All positive results for HCV-infection by rapid testing were confirmed by enzyme-linked immunosorbent assay (ELISA). HCV-RNA was detectable in 79.7%. Genotyping showed a predominance of genotype 1 (52%) followed by genotype 3 (34%) and genotype 4 (10%). Four patients (4%) had an intergenotype mixed infection. Subtyping showed the presence of six different HCV subtypes as follows: 1a (53.2%), 1b (6.4%), 3a (33.0%), 4a (3.2%), and 4d (4.3%). This is the first study describing circulating HCV genotypes among PWID in Tunisia. The distribution of HCV genotypes is distinct from the general population with a predominance of subtypes 1a and 3a. These findings can be used to guide national efforts aiming to optimize the access of PWID to relevant HCV prevention and treatment measures including pangenotypic regimens for patients infected with HCV genotype 3.

Project description:BACKGROUND & AIMS:Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10?years. METHODS:We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS:At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10?years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10?years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS:The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY:Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Dataset Information

Mathematical modeling of hepatitis c virus (HCV) prevention among people who inject drugs: A review of the literature and insights for elimination strategies.

Publications

Mathematical modeling of hepatitis c virus (HCV) prevention among people who inject drugs: A review of the literature and insights for elimination strategies.

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