Hepatitis C virus prevention and care for drug injectors: the French approach

Hepatitis C virus prevention and care for drug injectors: the French approach After France removed hepatitis C treatment reimbursement restrictions on 25 May 2016, an expert report presented recommendations, which focused on vulnerable groups including people who inject drugs (PWID). This commentary presents the key points of the chapter with a particular focus on policy. Thanks to the official lifting of restrictions based on disease stage and to the excellent efficacy and tolerance of the new DAA (Direct-Acting Antivirals) among PWID, the main issue is to improve the HCV care cascade. In France, many HCV-infected PWID, especially active/current PWID, remain undiagnosed and unlinked to care. Our challenge is to improve HCV screening by point of care testing (POCT), outreach methods with mobile teams, rapid tests, FibroScan, etc. and to provide PWID with appropriate services in all the settings they attend, such as drug treatment or harm reduction services, social services, prisons, etc. Another important issue is the prevention of reinfection through comprehensive and long-term follow-up. The report recommends a new national policy: testing and treating PWID as a priority, since this is the best way to eliminate HCV infection. It requires a global strategy consisting of combined and long-term interventions: prevention, outreach, screening, DAA, drug treatment programs including opiate substitution treatment (OST) and various harm reduction programs, including needle exchange programs (NEP). Ideally, these services should be delivered in the same place with an integrated approach. This should lead to meeting the national objective set by the government of eliminating hepatitis C by 2025. Keywords: Drug users, Injection, Guidelines, HCV, PWID, Harm reduction, Treatment costs, Strategy, France Hepatitis C virus prevention and care for drug in Western Europe [6]. It is even around 65% in France so injectors: the French approach the problem is particularly acute [7]. PWID pay a heavy The hepatitis C virus (HCV) epidemic is a major price for this infection in terms of mortality [8, 9] public health concern [1–3]. In France, the number and they are the primary source of HCV transmission of HCV-infected people was estimated at 193,000 in in France [4, 10]. 2011 [4]. Since then, more than 40,000 patients have benefited from the new treatments, the direct-acting Background antivirals (DAA), including 15,000 in 2016 and prob- For a long time, HCV treatments were not recom- ably 20,000 in 2017. The number of patients still mended for active PWID in France as in many other de- needing treatment is estimated at almost 115,000, of veloped countries or they were deferred and challenged whom about 75,000 have not yet been tested [5]. [11] for more or less explicit and acknowledged reasons. PWID are the main focus of attention particularly in These included lack of concern and involvement of PWID, developed countries, where the prevalence of infection professionals’ concerns about the frequent psychiatric co- (antibody anti-HCV positive) is estimated to be 53% morbidities, a particular intolerance to interferon as well as poor compliance with treatment [12]which is poten- * Correspondence: jm.delile@ceid-addiction.com tially worsened by social instability (absence of resi- Comité d’étude et d’information sur la drogue et les addictions (CEID), 20, dence, isolation, etc.), and worries about reinfection place Pey-Berland, 33000 Bordeaux, France Full list of author information is available at the end of the article [13]. However, very often treatment is deferred only © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 2 of 9 because PWID feel stigmatized, as is also the case with vulnerable groups like PWID [35]. PWID are an import- HIV infection [14]. ant population to target to improve HCV prevention The introduction of the DAA, which are simple to take, using the TasP approach. To this end, the ANRS and the effective and well-tolerated, has made it realistic to plan not CNS were mandated to make recommendations to en- only to cure most patients but also to control the HCV epi- sure that the most vulnerable groups and the furthest re- demic by reducing the risk of transmission [15, 16]. moved from healthcare services received the most Given the limited impact on HCV transmission of adequate HCV therapeutic management. In 2014 and current harm reduction interventions among PWID, it 2016, almost 200 clinicians, researchers, patients and seems that access to DAA will prove efficient in decreas- non-profit organizations were mobilized to produce the ing HCV-related morbidity and mortality among PWID, recommendations drafted in these two reports. as with HIV [17–19]. In combination with high coverage Our contribution to the report was to coordinate needle and syringe programs (HCNSP) and OST, treat- the chapter for proposing recommendations on PWID ing infected people with DAA is the best way to prevent and TasP. the spread of HCV and “to achieve substantial reduc- tions (> 50 %) in HCV chronic prevalence over 10 years.” Organization of care and follow-up of HCV-positive drug [15, 20, 21]. It would be feasible to envisage not only the users elimination of HCV infection but also its potential eradi- Our group was composed of clinicians (hepatologists, cation, an ail consistent with the concept of treatment as addiction specialists, general practitioners, psychologists prevention (TasP) [22–25]. and social workers), as well as researchers (epidemiologists Indeed, modeling studies [26–29] have shown that and social scientists), community representatives and drug HCV prevalence can be significantly reduced by treating users from self-support groups. To achieve our goal, we PWID infected with the virus, whereas the impact of harm needed to identify the foreseeable difficulties and organize reduction interventions (OST or needle exchange pro- access to DAA for PWID in the most efficient manner. In- grams, NEP) remains limited [30]. The TasP approach is terventions should be well adapted and all-encompassing also cost-effective [16]. The maximum effect is obtained to successfully engage and maintain PWID in treatment by associating DAA and harm reduction interventions and care, as most people have psychiatric comorbidities such as OST and NEP [21, 31]. and social vulnerabilities which make access to care With regard to DAA availability, Cousien et al. used a and follow-up particularly challenging [13, 36]. Positive dynamic individual-based model including the PWID so- results often depend on personalized assistance [12]. cial network to simulate the impact of improved testing, To overcome these limitations, therapeutic progress linkage to care, adherence to treatment and modified should be accompanied by validated harm reduction in- treatment recommendations on the transmission and terventions [21] that provide a real continuum of care. the morbidity of HCV infection in PWID in France. This was the basis for the working group’s recommenda- With the current incidence and cascade of care, HCV tions, which are organized in four main topics: prevention, prevalence decreased from 42.8 to 24.9% (95% confi- testing, treatment and an integrated approach. dence interval: 24.8–24.9) after 10 years when treatment was initiated at fibrosis stage ≥F2. Changing treatment Drug use and healthcare provision: the French context initiation criteria to treat from F0 was the only interven- As defined by OEDT/EMCDDA (Observatoire Européen tion leading to a substantial additional decrease in HCV des Drogues et des Toxicomanies/European Monitoring prevalence, which fell to 11.6% (95% CI: 11.6–11.7) at Center for Drugs and Drug Addiction), problematic drug 10 years. Combining this change with improved testing, users are those who use opiates, cocaine, crack, am- linkage to care and adherence to treatment decreased phetamines, and people on OST (opioid substitution HCV prevalence to 7.0% (95% CI: 7.0–7.1) at 10 years treatment), as well as those who injected their drugs in and avoided 15% (95% CI: 14–17) and 29% (95% CI: the previous month. This is one of the five EMCDDA key 28–30) of cirrhosis complications over 10 and 40 years, indicators required in the European Union countries. respectively [32, 33]. France is in the higher half of the European Union In this context, and following the first report on viral countries for problematic drug use (Janssen & Bastianic, hepatitis [34] which concluded the third national action 2013) with an estimated 275,000 to 360,000 users (includ- plan to fight HCV and HBV, the French Ministry of ing 105,000 injectors) and a prevalence estimated at 7‰ Health decided in May 2016 to grant universal access to and 9‰ (15 to 64 years old) [37]. Addiction care is mainly DAA, which were until then reserved for patients pre- given in 430 specialized centers (CSAPA, Centre de soins, senting a high degree of fibrosis. The ministry commis- d’accompagnement et de prévention en addictologie) sioned a second report with updated recommendations countrywide. These outpatient care services run by multi- for effectively reaching all affected people, especially the disciplinary teams treated around 280,000 people in Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 3 of 9 2014, including 80,000 for drug-related problems other than (individually tailored support and education for safer in- cannabis such as heroin and opiate abuse (Palle, 2016). jection), seem very promising [42, 43]. By observing users’ injecting practices, they can be given face-to-face Prevention information on safer ways to inject depending on their Interventions must address the risk of contamination by personal behavior. Moreover, France has recently de- emphasizing prevention and harm reduction. In 2014 cided to experiment drug consumption rooms (DCR). the number of PWID in France was estimated at 105000 Whether fixed or mobile, DCR can be tested in different with at least one injection during the previous year, in- sites and with high-risk marginalized populations like cluding 85,000 active injectors, i.e. at least one injection “squatters” and recent immigrants, especially those from during the previous month, including 35,770 who were Eastern Europe. AERLI can thus be given in DCR. The monitored by a CSAPA in 2014. Of these, 27,674 were Health Decree of January 27, 2016 authorized the imple- active injectors (Janssen, 2016). Some of the injectors mentation of three experimental DCR in France for the who do not go to the CSAPAs go to harm reduction next 6 years. The first two opened in 2016 in Paris and units in the CAARUD (Centre d’accueil et d’accompag- Strasburg, to be followed by Bordeaux in 2019. However, nement à la réduction des risques pour les usagers de more than three DCR will be needed in the future. drogues). However, special attention is required for those furthest away from the CAARUD, e.g. women, Testing for HCV infection young people, prisoners, migrants, rural residents, slam- Routine HCV testing is essential as it functions on two mers, etc. through adapted programs created for these levels: first, it reduces HCV incidence as knowing one’s vulnerable groups. Recent data has shown that, on aver- status helps to reduce risky behaviors [44, 45]; second, it age, a third of PWID visiting CAARUD (75,000 in 2014) makes it easier to locate people who could benefit from in French urban areas had difficulty getting new syringes in treatment, which is a another way to reduce HCV preva- the previous 6 months [7]. Nevertheless, the CAARUD still lence and therefore transmission. To date, many PWID form the backbone of NEP in France with nearly 7 million have not been screened including recent injectors, syringes distributed every year compared with fewer than PWID from vulnerable groups, but also occasional users 5 million in pharmacies [38]. Therefore, it is crucial to or ex-users who are often socialized, not in touch with a continue to develop the CAARUD since they provide ac- CSAPA or a CAARUD or no longer, and for whom gen- cess to information, education about safer injection and eral practitioners end up being the main link to care. provide injection, inhalation and snorting equipment. Additionally, an investigation carried out in several As the Amsterdam study demonstrated [39], combin- CAARUD and CSAPA indicated that although more ing OST with integrated harm reduction interventions than 9 PWID out of 10 are screened during their life- like NEP and allowing safer injection practices can in- time, one third and especially the recent ones are un- deed have a beneficial effect on the reduction of HCV aware of their HCV positivity [46]. The people and transmission. Moreover, OST contributes indirectly to centers who are in contact with PWID, as well as the harm reduction by increasing access to care and encour- treatment providers, harm reduction centers, and social aging better compliance [40]. It has been shown that workers must therefore do more to increase screening to OST is associated with a 50% reduction in the risk of reach the patients who could be treated with DAA. new HCV acquisition, and this effect is increased to 74% More outreach with mobile teams is needed wherever by the concomitant use of clean drug injecting equip- users gather, including squats, festivals, etc. Therefore, ment [31, 41]. The premature discontinuation of HCV promoting provider-initiated testing and counselling treatments is more frequent among “active” PWID who (PITC) (WHO, 2007) in the prevention or care centers are currently injecting and not enrolled in OST. In 2014, where PWID gather is essential (Morano, 2016). around 180,000 people in France were enrolled in OST, AERLI has helped to increase uptake of HCV testing of whom 150,000 were seen in an urban medical practice [43, 47]. The new rapid testing methods are therefore (105,000 with buprenorphine HD, 45000 with metha- valuable. In 2014, the French Health Authority (HAS, done), and 50,000 in a CSAPA (30,000 with methadone Haute Autorité pour la Santé) approved the use of a and 20,000 with buprenorphine HD), as well as 5000 in rapid HCV test as part of its HCV screening strategy prison with some patients receiving dual medical care, [48]. To improve screening, it is important to combine which is why the total number is greater than 180,000 counselling strategies with targeted tracking, POCT, out- (Brisacier, 2015). reach and rapid non-invasive tests. They are easy to im- A complementary approach is education about the plement and can reach many PWID [49], in particular safety of injections. The experimental programs in this the most marginalized. For example, the new molecular area like AERLI (accompagnement et education aux ris- testing kits that give a reading of HCV load by a simple ques liés à l’injection), which is equivalent to ITSESI hair sample and a drop of blood taken from the finger Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 4 of 9 are very promising [50]. General practitioners also have transmission [18, 21, 26, 58]. Therefore, one of the best a crucial role to play when it comes to another “hidden” strategies to reduce HCV transmission among PWID is to population, i.e. ex-drug users or “socialized” PWID, who treat them. DAA clinical trials classically exclude patients have potentially been contaminated for a long time but currently injecting, but they sometimes include phase 2 have moved away from the drug world (and therefore the and phase 3 OST patients. In this population, the reinfec- specialized centers), who are now socially well-adjusted tion rate after viral eradication is lower than that of the in- and are likely to go to a doctor’s office. The general popu- cidental rate, and the SVR rates among OST patients lation who may be in touch with “hidden” users should appear to be equivalent to those found in other patients also be made aware of how treatments have changed and [60–62]. No studies to date have reported problematic in- of the need for PWID to be treated without stigma. Many teractions between DAA and OST and adjustments of ex-PWID, including some who are infected with HCV, OST dosages do not seem necessary [41, 61, 63–66]. challenge and refuse testing and/or treatment as a denial Moreover, a recent study found that the longer the dur- of the past or because they fear former treatments that ation of OST (methadone), the better the capacity to con- were not well tolerated and which had little effect on tinue to receive HCV treatment and the better the SVR them. This fear is often based on ignorance of current rates [54]. Lastly, concomitant alcohol consumption does therapeutic progress and the new protocols, so it is im- not compromise the effectiveness of the treatment, so it is portant that they should be known about widely. not contraindicated, even though patients should be en- The data concerning screening frequency is limited, couraged to reduce their consumption. but given the high incidence of HCV infection among All these data led the health authorities to radically PWID in Europe [51] and the great benefit that may be change their policy, going from injection drug use being a expected, at least one annual screening is recommended criterion for exclusion [67] to making it a primary indica- for all PWID [52] and a screening every 6 months for tion in terms of public health objectives [25, 52, 60, 68]. active injectors, i.e. at least one injection in the current Therefore in June 2016, the HAS officially declared that month. On the other hand, once contamination has oc- “in an integrative approach to control the HCV epidemic, curred, HCV morbidity and mortality can only be re- the patients at highest risk of virus transmission, drug duced by treatment [17]. users and others likely to disseminate HCV infection should be able to benefit from these new DAA treatments, Accessing HCV care regardless of their level of hepatic fibrosis” [69]. This pos- Various studies summarized in a recent review [49]dem- ition was endorsed in their recommendations published onstrate the benefit of providing DAA treatment at sites December 2016 following the expert report that same year used by PWID. People living far away from hospitals and by the new professional recommendations of the should also have access to the new treatments. The teams French Hepatology Society (AFEF) published in March 2018. should adapt their offer to these new patients living fur- These recommendations are supported by the Francophone thest away from care settings and provide external help Infectious Pathology Society (SPILF), which incorporated the through mobile programs, particularly in rural areas [53] simplified therapeutic recommendations made possible by and at GPs’ offices [54]. the new pangenotypic treatments (http://www.afef.asso.fr/ ckfinder/userfiles/files/recommandations-textes-officiels/ Eligibility for care recommandations/VF%20INTERACTIF-%20RECO-VHC In the past, HCV treatments were not recommended for %20AFEF.pdf) and by the latest European guidelines (EASL active PWID or they were deferred and debated [11]. How- 2018, https://doi.org/10.1016/j.jhep.2018.03.026)[41]. ever, current data show that PWID benefit considerably from DAA because they have a higher risk of HCV trans- Treatment initiation mission and often have a sustained viral response (SVR) Therapeutic pre-evaluation should be multidisciplinary when given adapted comprehensive care [49, 55]and are to provide the most comprehensive care including addic- enrolled in an OST program [56]. Therefore, treatment is tion treatment like OST, harm reduction awareness, recommended in France for all infected PWID regardless hepatic care, psychological support and social services. of their fibrosis level. The goal is to obtain an SVR (un- Psychosocial interventions that are designed for patients, detectable HCV RNA 3 months post-treatment). Studies of their entourage and health professionals can facilitate classical treatments (pegylated interferon-ribavirin) show the initiation of HCV treatment by creating the frame- equivalent rates of SVR with PWID including active work for an integrated approach, particularly if the pa- injectors and other patients [57–59]. Treatment by tient has psychiatric comorbidities [12, 56, 70]. PWID DAA without interferon of a shorter duration is very are more likely to adhere to HCV treatment if they are well tolerated and effective, and major benefit can be introduced to them by their entourage, most likely social expected, in particular in terms of preventing HCV workers or peers, in settings where their drug addiction Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 5 of 9 problems are understood [71, 72]. HCV infection is a based mainly on the strategy as mentioned above, in- chronic liver disease with a risk of cirrhosis. Therefore, cluding the combination of OST and NEP. The risk of patients should be offered non-invasive evaluation of re-infection is a major issue as new contamination can liver fibrosis with blood markers such as the FibroTest limit the preventive effect of treatment. It can also or liver stiffness measurement like the FibroScan. In have a negative psychological impact on patients the event of cirrhosis, abdominal ultrasonography is themselves, as some professionals may be reticent to needed every 6 months for hepatocellular carcinoma prescribe future access to treatments. However, recent screening, even after a sustained virologic response is data from seven studies [84]including theAmsterdam obtained. cohort study [85] is reassuring, highlighting the relatively low rates of re-infection in treated PWID ranging Treatment adherence and compliance from 0.8 to 4.7% person-year. These relatively low In principle, compliance with DAA should be easier than rates may be due in part to the conditions of the with the former treatments: better tolerance, fewer pills former treatments (pegylated interferon-ribavirin) which to take, simpler and less restrictive treatment, shorter required a well-selected compliant population receiving a duration of treatment. Adherence is much better if the high-level intervention [85]. motivation to initiate treatment has been strengthened. The question arises, however, as to the outcomes of Supervised administration of medication can also im- people living far from the treatment centers, who do prove compliance [56], in particular in OST programs not really request treatment or even have a clinically [73]. Other studies have shown that compliance is also identified pathology, are potentially more unstable and improved by multidisciplinary approaches [74] involving marginal, and are still injecting. One can assume that nurses [75] and psycho-educational techniques [76]. they will be at high risk of re-infection, so harm reduc- tion interventions will likely require a specific module Integrated care for preventing re-infection. As stated by Andrew Ball Experience with AIDS has shown that the quality of addic- [82, 86], drug use is associated with multiple and chan- tion treatment and its associated disorders is a key factor ging health risks and harms that require diverse and in patients’ involvement in their treatment, as it im- complex responses. In an integrated approach, harm re- proves compliance at a level similar to that in non-HCV duction comprises a set of interventions that can be patients [77, 78]. Drug services and hepatic care should adapted to various places and to people with specific be located in the same place.Therefore,the CSAPA needs. A harm reduction package could combine DAA, and CAARUD provide a full range of care to patients. OST, NEP, ITSESI, fixed and mobile DCRs, psychosocial Although their technical infrastructure may be limited, support and peer interventions as well as an advocacy these frontline facilities contribute to improving screen- component for social changes aiming at reducing the ing rates and encouraging patients to attend consulta- stigma surrounding PWID. The impact of HCV treat- tions regularly, as well providing access to hepatic care. ments is increased when they are combined with preven- Some offer full liver examinations onsite, a factor which tion, harm reduction interventions and care. Similarly, an contributes to better compliance [79]. They also have a increase in the positive effects of HIV and HCV treat- favorable impact on treatment and the prevention of ments has been observed when they are associated recontamination. They are essential components of the with better access to drug treatment and social services harm reduction arsenal, because their approach is [56, 87, 88]. Peer involvement is also an essential asset, multidisciplinary [80]. as demonstrated by the web platform “Hepatitis”,man- The comprehensive “one-stop shop” offered in the aged in France by a PWID support group (Auto-support usa- CSAPA and CAARUD consists of global HCV testing and gers de drogues, ASUD, http://www.asud.org/hepatite-c/). treatment, [81], hepatologic consultation, treatment initi- Support from the Aides Federation has also been cru- ation and follow-up. Once a cure is achieved, follow-up is cial to cope with the emerging HCV epidemic in HIV- annual. In the event of cirrhosis, it is performed every six positive men who have sex with men, where a particularly months and should include sonographic screening for high level of reinfection seems to exist according to the hepatic carcinoma. NEAT data (European AIDS Treatment Network). Therefore, harm reduction, treatment and prevention Prevention of re-infection: harm reduction as a are complementary: harm reduction interventions pro- comprehensive intervention [82, 83] mote access to treatment and healthcare reinforces the Unlike a relapse, recontamination is a new HCV infec- effectiveness of harm reduction [89]. The maximum ef- tion resulting from continued risky injection practices fect is therefore obtained by a combined approach asso- or resumptionofdrug injectionuse,despiteacureof ciating DAA and harm reduction (OST and NEP) [21]in the previous infection. Prevention of re-infection is a continuum of care and prevention [68]. Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 6 of 9 Exceptional funding treatments make it possible to treat all patients effectively Universal access to the new HCV treatments is costly. as well as to envisage the eradication of HCV infection by Approximately 750 million € have been invested in HCV treating all infected PWID. To achieve elimination of HCV each year since 2015, which made it possible to treat and to avoid HCV reinfection, it is also crucial to nearly 15,000 patients per year. At this pace, the epi- strengthen and extend harm reduction policies. These pub- demic in France could be eradicated in about ten years. lic health objectives require an outreach to people with se- To limit this considerable burden on public finances, the vere psychosocial vulnerabilities, who often live far from government has set up a unique tax mechanism, named care facilities or harm reduction services. The programs W, which fixes a ceiling on industrial profits. If the ex- should be adapted to facilitate access to testing and treat- penditure generated by treatments exceeds this budget ment, and to support the monitoring and prevention of re- (a reference amount W), the surplus would be taxed at infection. The present recommendations are based on the 100% so no additional public expenditure would be re- international consensus and data showing that treating quired. In addition, very strict price negotiations have PWID is easily achievable and effective. This should con- made it possible to obtain less exorbitant drug prices, tribute to making treatment efficient and available through- given the arrival of new molecules on the market which out France. This should lead to meeting the national circumvented Gilead’s monopoly with Sovaldi®. In April objective set by the government of eliminating hepatitis C 2017, new prices were fixed: under 28,700 €, versus 41,000 by 2025 in accordance with the WHO strategy [2, 3]. € previously. A similar agreement has been reached for the pangenotypic medications which were launched in Recommendations 2017 and 2018 (Epclusa® and Maviret®). Simplified, pan- genotypic anti-HCV treatment recommendations are now 1: PWID should be routinely tested for HCV every possible [41]. Furthermore, provisions concerning num- 12 months and active PWID (at least one injection bers have been made. If the number of patients being during the past month) every six months. treated were to increase, which is the public health goal, 2: Given its benefits on the reduction of transmission, the cost per unit would decrease accordingly. This would treatment is recommended for all PWID with allow better control of overall expenditure. The W mech- chronic HCV infection. anism should not need to be triggered, nor should prices 3: Cessation of injection is not a requirement of HCV need to be fixed. However, if necessary, these deterrents treatment. would remain available. With this financial framework in 4: PWID should receive anpre-therapeutic HCV place, the strategy proposed in the expert report and the assessment which includes a multidisciplinary HAS recommendations of December 2016 that followed evaluation of psychosocial status and drug and it, it would be possible to reimburse DAA fully in France. alcohol use, allowing for an integrated follow-up. Furthermore, it was decided in March 2018 that the new 5: PWID should receive individualized HCV treatment pangenotypic drugs could henceforth be delivered in phar- in a clinical setting enabling access to a macies and no longer only in hospitals. multidisciplinary team including drug and alcohol The next step will be to increase the number of pre- services, as well as psychiatric and social services, if scribing physicians, which is currently limited to hospital possible in a single location. gastroenterologists, hepatologists, and specialists of in- 6: Harm reduction information and counselling should ternal medicine and infectious diseases. To move towards be provided during HCV treatment to prevent HCV the recommendations of the expert report and to be able re-infection after a successful treatment, especially to implement the ministry’s decision, the abovementioned with PWID who exhibit ongoing risk-behaviors. treatment strategy should be able to be prescribed not 7: Following SVR, screening for HCV re-infection in only by these specialists but also by the clinicians working PWID should be performed yearly with HCV RNA. in the CSAPA and CAARUD and by general practitioners who are members of the hepatitis networks. Such a meas- This research did not receive any special grant from ure is likely to be taken in May 2018. funding agencies in the public, commercial or not-for-profit sectors. Conclusion Major decreases in prevalent HCV infections occur only Endnotes when treatment is initiated at the early stages of fibrosis, Jean-Michel Delile (coordinator), Xavier Aknine, Antoine suggesting that systematic treatment of PWID would be Bachelard, Georges Brousse, Michel Doffoel, Stéphanie beneficial. However, elimination of HCV within the next Dominguez, Juliette Foucher, Marie Jauffret-Roustide, 10 years will be difficult to achieve by treatment alone, Martine Lacoste, Pascal Mélin, Sébastien Mouveroux, even with a much-improved offer of care. The new HCV Fabrice Olivet, Brigitte Reiller, Perrine Roux, Gilles Rozsypal, Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 7 of 9 Acknowledgements 7. Weill-Barillet L, Pillonel J, Semaille C, Léon L, Le Strat Y, Pascal X, Barin F, We wish to acknowledge all the members of the French working group Jauffret-Roustide M. Hepatitis C virus and HIV seroprevalences, (“Organization of the care and follow-up of HCV-positive drug users.”) sociodemographic characteristics, behaviors and access to syringes among who contributed to the recommendations presented in this article. All drug users, a comparison of geographical areas in France, ANRS-Coquelicot are mentioned in the manuscript: 2011 survey. Rev Epidemiol Sante Publique. 2016;64(4):301–12. Xavier Aknine, general practitioner, Gagny; Antoine Bachelard, University 8. Grebely J, Raffa JD, Lai C, Kerr T, Fischer B, Krajden M, Dore GJ, Tyndall MW. Hospital, Créteil; Georges Brousse, University Hospital, Clermont-Ferrand; Impact of hepatitis C virus infection on all-cause and liver-related mortality Michel Doffoel, University Hospital, Strasbourg; Stéphanie Dominguez, in a large community-based cohort of inner city residents. J Viral Hepat. University Hospital, Créteil; Martine Lacoste, Clémence Isaure regional 2011;18(1):32–41. Association, Toulouse; Pascal Mélin, SOS Hepatitis Association, Bagnolet; 9. Yu A, Spinelli JJ, Cook DA, Buxton JA, Krajden M. Mortality among British Sébastien Mouveroux, Aides Association, Pantin; Fabrice Olivet, Drug Columbians testing for hepatitis C antibody. BMC Public Health. 2013;13:291. Users Support group ASUD, Paris; Gilles Rozsypal, Merlet Farm (CEID), 10. Czernichow P. Hépatites B et C : mieux savoir pour mieux agir. Bull Saint-Martin-de-Laye. Epidemiol Hebd. 2016;13-14:222–3. We also thank Ray Cooke who provided editorial assistance. 11. Hepworth J, Bain T, van Driel M. Hepatitis C, mental health and equity of access to antiviral therapy: a systematic narrative review. Int J Equity Health. 2013;12(1):1–8. Authors’ contributions 12. Schaefer M, Sarkar R, Diez-Quevedo C. Management of Mental Health JMD conceived the study and drafted the manuscript. 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Treatment for hepatitis C virus infection among people who inject drugs attending opioid substitution treatment and community health clinics: the ETHOS study. Addiction. 2016;111(2):311–9. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology, Medicine and Policy Springer Journals

Hepatitis C virus prevention and care for drug injectors: the French approach

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Abstract

After France removed hepatitis C treatment reimbursement restrictions on 25 May 2016, an expert report presented recommendations, which focused on vulnerable groups including people who inject drugs (PWID). This commentary presents the key points of the chapter with a particular focus on policy. Thanks to the official lifting of restrictions based on disease stage and to the excellent efficacy and tolerance of the new DAA (Direct-Acting Antivirals) among PWID, the main issue is to improve the HCV care cascade. In France, many HCV-infected PWID, especially active/current PWID, remain undiagnosed and unlinked to care. Our challenge is to improve HCV screening by point of care testing (POCT), outreach methods with mobile teams, rapid tests, FibroScan, etc. and to provide PWID with appropriate services in all the settings they attend, such as drug treatment or harm reduction services, social services, prisons, etc. Another important issue is the prevention of reinfection through comprehensive and long-term follow-up. The report recommends a new national policy: testing and treating PWID as a priority, since this is the best way to eliminate HCV infection. It requires a global strategy consisting of combined and long-term interventions: prevention, outreach, screening, DAA, drug treatment programs including opiate substitution treatment (OST) and various harm reduction programs, including needle exchange programs (NEP). Ideally, these services should be delivered in the same place with an integrated approach. This should lead to meeting the national objective set by the government of eliminating hepatitis C by 2025. Keywords: Drug users, Injection, Guidelines, HCV, PWID, Harm reduction, Treatment costs, Strategy, France Hepatitis C virus prevention and care for drug in Western Europe [6]. It is even around 65% in France so injectors: the French approach the problem is particularly acute [7]. PWID pay a heavy The hepatitis C virus (HCV) epidemic is a major price for this infection in terms of mortality [8, 9] public health concern [1–3]. In France, the number and they are the primary source of HCV transmission of HCV-infected people was estimated at 193,000 in in France [4, 10]. 2011 [4]. Since then, more than 40,000 patients have benefited from the new treatments, the direct-acting Background antivirals (DAA), including 15,000 in 2016 and prob- For a long time, HCV treatments were not recom- ably 20,000 in 2017. The number of patients still mended for active PWID in France as in many other de- needing treatment is estimated at almost 115,000, of veloped countries or they were deferred and challenged whom about 75,000 have not yet been tested [5]. [11] for more or less explicit and acknowledged reasons. PWID are the main focus of attention particularly in These included lack of concern and involvement of PWID, developed countries, where the prevalence of infection professionals’ concerns about the frequent psychiatric co- (antibody anti-HCV positive) is estimated to be 53% morbidities, a particular intolerance to interferon as well as poor compliance with treatment [12]which is poten- * Correspondence: jm.delile@ceid-addiction.com tially worsened by social instability (absence of resi- Comité d’étude et d’information sur la drogue et les addictions (CEID), 20, dence, isolation, etc.), and worries about reinfection place Pey-Berland, 33000 Bordeaux, France Full list of author information is available at the end of the article [13]. However, very often treatment is deferred only © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 2 of 9 because PWID feel stigmatized, as is also the case with vulnerable groups like PWID [35]. PWID are an import- HIV infection [14]. ant population to target to improve HCV prevention The introduction of the DAA, which are simple to take, using the TasP approach. To this end, the ANRS and the effective and well-tolerated, has made it realistic to plan not CNS were mandated to make recommendations to en- only to cure most patients but also to control the HCV epi- sure that the most vulnerable groups and the furthest re- demic by reducing the risk of transmission [15, 16]. moved from healthcare services received the most Given the limited impact on HCV transmission of adequate HCV therapeutic management. In 2014 and current harm reduction interventions among PWID, it 2016, almost 200 clinicians, researchers, patients and seems that access to DAA will prove efficient in decreas- non-profit organizations were mobilized to produce the ing HCV-related morbidity and mortality among PWID, recommendations drafted in these two reports. as with HIV [17–19]. In combination with high coverage Our contribution to the report was to coordinate needle and syringe programs (HCNSP) and OST, treat- the chapter for proposing recommendations on PWID ing infected people with DAA is the best way to prevent and TasP. the spread of HCV and “to achieve substantial reduc- tions (> 50 %) in HCV chronic prevalence over 10 years.” Organization of care and follow-up of HCV-positive drug [15, 20, 21]. It would be feasible to envisage not only the users elimination of HCV infection but also its potential eradi- Our group was composed of clinicians (hepatologists, cation, an ail consistent with the concept of treatment as addiction specialists, general practitioners, psychologists prevention (TasP) [22–25]. and social workers), as well as researchers (epidemiologists Indeed, modeling studies [26–29] have shown that and social scientists), community representatives and drug HCV prevalence can be significantly reduced by treating users from self-support groups. To achieve our goal, we PWID infected with the virus, whereas the impact of harm needed to identify the foreseeable difficulties and organize reduction interventions (OST or needle exchange pro- access to DAA for PWID in the most efficient manner. In- grams, NEP) remains limited [30]. The TasP approach is terventions should be well adapted and all-encompassing also cost-effective [16]. The maximum effect is obtained to successfully engage and maintain PWID in treatment by associating DAA and harm reduction interventions and care, as most people have psychiatric comorbidities such as OST and NEP [21, 31]. and social vulnerabilities which make access to care With regard to DAA availability, Cousien et al. used a and follow-up particularly challenging [13, 36]. Positive dynamic individual-based model including the PWID so- results often depend on personalized assistance [12]. cial network to simulate the impact of improved testing, To overcome these limitations, therapeutic progress linkage to care, adherence to treatment and modified should be accompanied by validated harm reduction in- treatment recommendations on the transmission and terventions [21] that provide a real continuum of care. the morbidity of HCV infection in PWID in France. This was the basis for the working group’s recommenda- With the current incidence and cascade of care, HCV tions, which are organized in four main topics: prevention, prevalence decreased from 42.8 to 24.9% (95% confi- testing, treatment and an integrated approach. dence interval: 24.8–24.9) after 10 years when treatment was initiated at fibrosis stage ≥F2. Changing treatment Drug use and healthcare provision: the French context initiation criteria to treat from F0 was the only interven- As defined by OEDT/EMCDDA (Observatoire Européen tion leading to a substantial additional decrease in HCV des Drogues et des Toxicomanies/European Monitoring prevalence, which fell to 11.6% (95% CI: 11.6–11.7) at Center for Drugs and Drug Addiction), problematic drug 10 years. Combining this change with improved testing, users are those who use opiates, cocaine, crack, am- linkage to care and adherence to treatment decreased phetamines, and people on OST (opioid substitution HCV prevalence to 7.0% (95% CI: 7.0–7.1) at 10 years treatment), as well as those who injected their drugs in and avoided 15% (95% CI: 14–17) and 29% (95% CI: the previous month. This is one of the five EMCDDA key 28–30) of cirrhosis complications over 10 and 40 years, indicators required in the European Union countries. respectively [32, 33]. France is in the higher half of the European Union In this context, and following the first report on viral countries for problematic drug use (Janssen & Bastianic, hepatitis [34] which concluded the third national action 2013) with an estimated 275,000 to 360,000 users (includ- plan to fight HCV and HBV, the French Ministry of ing 105,000 injectors) and a prevalence estimated at 7‰ Health decided in May 2016 to grant universal access to and 9‰ (15 to 64 years old) [37]. Addiction care is mainly DAA, which were until then reserved for patients pre- given in 430 specialized centers (CSAPA, Centre de soins, senting a high degree of fibrosis. The ministry commis- d’accompagnement et de prévention en addictologie) sioned a second report with updated recommendations countrywide. These outpatient care services run by multi- for effectively reaching all affected people, especially the disciplinary teams treated around 280,000 people in Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 3 of 9 2014, including 80,000 for drug-related problems other than (individually tailored support and education for safer in- cannabis such as heroin and opiate abuse (Palle, 2016). jection), seem very promising [42, 43]. By observing users’ injecting practices, they can be given face-to-face Prevention information on safer ways to inject depending on their Interventions must address the risk of contamination by personal behavior. Moreover, France has recently de- emphasizing prevention and harm reduction. In 2014 cided to experiment drug consumption rooms (DCR). the number of PWID in France was estimated at 105000 Whether fixed or mobile, DCR can be tested in different with at least one injection during the previous year, in- sites and with high-risk marginalized populations like cluding 85,000 active injectors, i.e. at least one injection “squatters” and recent immigrants, especially those from during the previous month, including 35,770 who were Eastern Europe. AERLI can thus be given in DCR. The monitored by a CSAPA in 2014. Of these, 27,674 were Health Decree of January 27, 2016 authorized the imple- active injectors (Janssen, 2016). Some of the injectors mentation of three experimental DCR in France for the who do not go to the CSAPAs go to harm reduction next 6 years. The first two opened in 2016 in Paris and units in the CAARUD (Centre d’accueil et d’accompag- Strasburg, to be followed by Bordeaux in 2019. However, nement à la réduction des risques pour les usagers de more than three DCR will be needed in the future. drogues). However, special attention is required for those furthest away from the CAARUD, e.g. women, Testing for HCV infection young people, prisoners, migrants, rural residents, slam- Routine HCV testing is essential as it functions on two mers, etc. through adapted programs created for these levels: first, it reduces HCV incidence as knowing one’s vulnerable groups. Recent data has shown that, on aver- status helps to reduce risky behaviors [44, 45]; second, it age, a third of PWID visiting CAARUD (75,000 in 2014) makes it easier to locate people who could benefit from in French urban areas had difficulty getting new syringes in treatment, which is a another way to reduce HCV preva- the previous 6 months [7]. Nevertheless, the CAARUD still lence and therefore transmission. To date, many PWID form the backbone of NEP in France with nearly 7 million have not been screened including recent injectors, syringes distributed every year compared with fewer than PWID from vulnerable groups, but also occasional users 5 million in pharmacies [38]. Therefore, it is crucial to or ex-users who are often socialized, not in touch with a continue to develop the CAARUD since they provide ac- CSAPA or a CAARUD or no longer, and for whom gen- cess to information, education about safer injection and eral practitioners end up being the main link to care. provide injection, inhalation and snorting equipment. Additionally, an investigation carried out in several As the Amsterdam study demonstrated [39], combin- CAARUD and CSAPA indicated that although more ing OST with integrated harm reduction interventions than 9 PWID out of 10 are screened during their life- like NEP and allowing safer injection practices can in- time, one third and especially the recent ones are un- deed have a beneficial effect on the reduction of HCV aware of their HCV positivity [46]. The people and transmission. Moreover, OST contributes indirectly to centers who are in contact with PWID, as well as the harm reduction by increasing access to care and encour- treatment providers, harm reduction centers, and social aging better compliance [40]. It has been shown that workers must therefore do more to increase screening to OST is associated with a 50% reduction in the risk of reach the patients who could be treated with DAA. new HCV acquisition, and this effect is increased to 74% More outreach with mobile teams is needed wherever by the concomitant use of clean drug injecting equip- users gather, including squats, festivals, etc. Therefore, ment [31, 41]. The premature discontinuation of HCV promoting provider-initiated testing and counselling treatments is more frequent among “active” PWID who (PITC) (WHO, 2007) in the prevention or care centers are currently injecting and not enrolled in OST. In 2014, where PWID gather is essential (Morano, 2016). around 180,000 people in France were enrolled in OST, AERLI has helped to increase uptake of HCV testing of whom 150,000 were seen in an urban medical practice [43, 47]. The new rapid testing methods are therefore (105,000 with buprenorphine HD, 45000 with metha- valuable. In 2014, the French Health Authority (HAS, done), and 50,000 in a CSAPA (30,000 with methadone Haute Autorité pour la Santé) approved the use of a and 20,000 with buprenorphine HD), as well as 5000 in rapid HCV test as part of its HCV screening strategy prison with some patients receiving dual medical care, [48]. To improve screening, it is important to combine which is why the total number is greater than 180,000 counselling strategies with targeted tracking, POCT, out- (Brisacier, 2015). reach and rapid non-invasive tests. They are easy to im- A complementary approach is education about the plement and can reach many PWID [49], in particular safety of injections. The experimental programs in this the most marginalized. For example, the new molecular area like AERLI (accompagnement et education aux ris- testing kits that give a reading of HCV load by a simple ques liés à l’injection), which is equivalent to ITSESI hair sample and a drop of blood taken from the finger Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 4 of 9 are very promising [50]. General practitioners also have transmission [18, 21, 26, 58]. Therefore, one of the best a crucial role to play when it comes to another “hidden” strategies to reduce HCV transmission among PWID is to population, i.e. ex-drug users or “socialized” PWID, who treat them. DAA clinical trials classically exclude patients have potentially been contaminated for a long time but currently injecting, but they sometimes include phase 2 have moved away from the drug world (and therefore the and phase 3 OST patients. In this population, the reinfec- specialized centers), who are now socially well-adjusted tion rate after viral eradication is lower than that of the in- and are likely to go to a doctor’s office. The general popu- cidental rate, and the SVR rates among OST patients lation who may be in touch with “hidden” users should appear to be equivalent to those found in other patients also be made aware of how treatments have changed and [60–62]. No studies to date have reported problematic in- of the need for PWID to be treated without stigma. Many teractions between DAA and OST and adjustments of ex-PWID, including some who are infected with HCV, OST dosages do not seem necessary [41, 61, 63–66]. challenge and refuse testing and/or treatment as a denial Moreover, a recent study found that the longer the dur- of the past or because they fear former treatments that ation of OST (methadone), the better the capacity to con- were not well tolerated and which had little effect on tinue to receive HCV treatment and the better the SVR them. This fear is often based on ignorance of current rates [54]. Lastly, concomitant alcohol consumption does therapeutic progress and the new protocols, so it is im- not compromise the effectiveness of the treatment, so it is portant that they should be known about widely. not contraindicated, even though patients should be en- The data concerning screening frequency is limited, couraged to reduce their consumption. but given the high incidence of HCV infection among All these data led the health authorities to radically PWID in Europe [51] and the great benefit that may be change their policy, going from injection drug use being a expected, at least one annual screening is recommended criterion for exclusion [67] to making it a primary indica- for all PWID [52] and a screening every 6 months for tion in terms of public health objectives [25, 52, 60, 68]. active injectors, i.e. at least one injection in the current Therefore in June 2016, the HAS officially declared that month. On the other hand, once contamination has oc- “in an integrative approach to control the HCV epidemic, curred, HCV morbidity and mortality can only be re- the patients at highest risk of virus transmission, drug duced by treatment [17]. users and others likely to disseminate HCV infection should be able to benefit from these new DAA treatments, Accessing HCV care regardless of their level of hepatic fibrosis” [69]. This pos- Various studies summarized in a recent review [49]dem- ition was endorsed in their recommendations published onstrate the benefit of providing DAA treatment at sites December 2016 following the expert report that same year used by PWID. People living far away from hospitals and by the new professional recommendations of the should also have access to the new treatments. The teams French Hepatology Society (AFEF) published in March 2018. should adapt their offer to these new patients living fur- These recommendations are supported by the Francophone thest away from care settings and provide external help Infectious Pathology Society (SPILF), which incorporated the through mobile programs, particularly in rural areas [53] simplified therapeutic recommendations made possible by and at GPs’ offices [54]. the new pangenotypic treatments (http://www.afef.asso.fr/ ckfinder/userfiles/files/recommandations-textes-officiels/ Eligibility for care recommandations/VF%20INTERACTIF-%20RECO-VHC In the past, HCV treatments were not recommended for %20AFEF.pdf) and by the latest European guidelines (EASL active PWID or they were deferred and debated [11]. How- 2018, https://doi.org/10.1016/j.jhep.2018.03.026)[41]. ever, current data show that PWID benefit considerably from DAA because they have a higher risk of HCV trans- Treatment initiation mission and often have a sustained viral response (SVR) Therapeutic pre-evaluation should be multidisciplinary when given adapted comprehensive care [49, 55]and are to provide the most comprehensive care including addic- enrolled in an OST program [56]. Therefore, treatment is tion treatment like OST, harm reduction awareness, recommended in France for all infected PWID regardless hepatic care, psychological support and social services. of their fibrosis level. The goal is to obtain an SVR (un- Psychosocial interventions that are designed for patients, detectable HCV RNA 3 months post-treatment). Studies of their entourage and health professionals can facilitate classical treatments (pegylated interferon-ribavirin) show the initiation of HCV treatment by creating the frame- equivalent rates of SVR with PWID including active work for an integrated approach, particularly if the pa- injectors and other patients [57–59]. Treatment by tient has psychiatric comorbidities [12, 56, 70]. PWID DAA without interferon of a shorter duration is very are more likely to adhere to HCV treatment if they are well tolerated and effective, and major benefit can be introduced to them by their entourage, most likely social expected, in particular in terms of preventing HCV workers or peers, in settings where their drug addiction Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 5 of 9 problems are understood [71, 72]. HCV infection is a based mainly on the strategy as mentioned above, in- chronic liver disease with a risk of cirrhosis. Therefore, cluding the combination of OST and NEP. The risk of patients should be offered non-invasive evaluation of re-infection is a major issue as new contamination can liver fibrosis with blood markers such as the FibroTest limit the preventive effect of treatment. It can also or liver stiffness measurement like the FibroScan. In have a negative psychological impact on patients the event of cirrhosis, abdominal ultrasonography is themselves, as some professionals may be reticent to needed every 6 months for hepatocellular carcinoma prescribe future access to treatments. However, recent screening, even after a sustained virologic response is data from seven studies [84]including theAmsterdam obtained. cohort study [85] is reassuring, highlighting the relatively low rates of re-infection in treated PWID ranging Treatment adherence and compliance from 0.8 to 4.7% person-year. These relatively low In principle, compliance with DAA should be easier than rates may be due in part to the conditions of the with the former treatments: better tolerance, fewer pills former treatments (pegylated interferon-ribavirin) which to take, simpler and less restrictive treatment, shorter required a well-selected compliant population receiving a duration of treatment. Adherence is much better if the high-level intervention [85]. motivation to initiate treatment has been strengthened. The question arises, however, as to the outcomes of Supervised administration of medication can also im- people living far from the treatment centers, who do prove compliance [56], in particular in OST programs not really request treatment or even have a clinically [73]. Other studies have shown that compliance is also identified pathology, are potentially more unstable and improved by multidisciplinary approaches [74] involving marginal, and are still injecting. One can assume that nurses [75] and psycho-educational techniques [76]. they will be at high risk of re-infection, so harm reduc- tion interventions will likely require a specific module Integrated care for preventing re-infection. As stated by Andrew Ball Experience with AIDS has shown that the quality of addic- [82, 86], drug use is associated with multiple and chan- tion treatment and its associated disorders is a key factor ging health risks and harms that require diverse and in patients’ involvement in their treatment, as it im- complex responses. In an integrated approach, harm re- proves compliance at a level similar to that in non-HCV duction comprises a set of interventions that can be patients [77, 78]. Drug services and hepatic care should adapted to various places and to people with specific be located in the same place.Therefore,the CSAPA needs. A harm reduction package could combine DAA, and CAARUD provide a full range of care to patients. OST, NEP, ITSESI, fixed and mobile DCRs, psychosocial Although their technical infrastructure may be limited, support and peer interventions as well as an advocacy these frontline facilities contribute to improving screen- component for social changes aiming at reducing the ing rates and encouraging patients to attend consulta- stigma surrounding PWID. The impact of HCV treat- tions regularly, as well providing access to hepatic care. ments is increased when they are combined with preven- Some offer full liver examinations onsite, a factor which tion, harm reduction interventions and care. Similarly, an contributes to better compliance [79]. They also have a increase in the positive effects of HIV and HCV treat- favorable impact on treatment and the prevention of ments has been observed when they are associated recontamination. They are essential components of the with better access to drug treatment and social services harm reduction arsenal, because their approach is [56, 87, 88]. Peer involvement is also an essential asset, multidisciplinary [80]. as demonstrated by the web platform “Hepatitis”,man- The comprehensive “one-stop shop” offered in the aged in France by a PWID support group (Auto-support usa- CSAPA and CAARUD consists of global HCV testing and gers de drogues, ASUD, http://www.asud.org/hepatite-c/). treatment, [81], hepatologic consultation, treatment initi- Support from the Aides Federation has also been cru- ation and follow-up. Once a cure is achieved, follow-up is cial to cope with the emerging HCV epidemic in HIV- annual. In the event of cirrhosis, it is performed every six positive men who have sex with men, where a particularly months and should include sonographic screening for high level of reinfection seems to exist according to the hepatic carcinoma. NEAT data (European AIDS Treatment Network). Therefore, harm reduction, treatment and prevention Prevention of re-infection: harm reduction as a are complementary: harm reduction interventions pro- comprehensive intervention [82, 83] mote access to treatment and healthcare reinforces the Unlike a relapse, recontamination is a new HCV infec- effectiveness of harm reduction [89]. The maximum ef- tion resulting from continued risky injection practices fect is therefore obtained by a combined approach asso- or resumptionofdrug injectionuse,despiteacureof ciating DAA and harm reduction (OST and NEP) [21]in the previous infection. Prevention of re-infection is a continuum of care and prevention [68]. Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 6 of 9 Exceptional funding treatments make it possible to treat all patients effectively Universal access to the new HCV treatments is costly. as well as to envisage the eradication of HCV infection by Approximately 750 million € have been invested in HCV treating all infected PWID. To achieve elimination of HCV each year since 2015, which made it possible to treat and to avoid HCV reinfection, it is also crucial to nearly 15,000 patients per year. At this pace, the epi- strengthen and extend harm reduction policies. These pub- demic in France could be eradicated in about ten years. lic health objectives require an outreach to people with se- To limit this considerable burden on public finances, the vere psychosocial vulnerabilities, who often live far from government has set up a unique tax mechanism, named care facilities or harm reduction services. The programs W, which fixes a ceiling on industrial profits. If the ex- should be adapted to facilitate access to testing and treat- penditure generated by treatments exceeds this budget ment, and to support the monitoring and prevention of re- (a reference amount W), the surplus would be taxed at infection. The present recommendations are based on the 100% so no additional public expenditure would be re- international consensus and data showing that treating quired. In addition, very strict price negotiations have PWID is easily achievable and effective. This should con- made it possible to obtain less exorbitant drug prices, tribute to making treatment efficient and available through- given the arrival of new molecules on the market which out France. This should lead to meeting the national circumvented Gilead’s monopoly with Sovaldi®. In April objective set by the government of eliminating hepatitis C 2017, new prices were fixed: under 28,700 €, versus 41,000 by 2025 in accordance with the WHO strategy [2, 3]. € previously. A similar agreement has been reached for the pangenotypic medications which were launched in Recommendations 2017 and 2018 (Epclusa® and Maviret®). Simplified, pan- genotypic anti-HCV treatment recommendations are now 1: PWID should be routinely tested for HCV every possible [41]. Furthermore, provisions concerning num- 12 months and active PWID (at least one injection bers have been made. If the number of patients being during the past month) every six months. treated were to increase, which is the public health goal, 2: Given its benefits on the reduction of transmission, the cost per unit would decrease accordingly. This would treatment is recommended for all PWID with allow better control of overall expenditure. The W mech- chronic HCV infection. anism should not need to be triggered, nor should prices 3: Cessation of injection is not a requirement of HCV need to be fixed. However, if necessary, these deterrents treatment. would remain available. With this financial framework in 4: PWID should receive anpre-therapeutic HCV place, the strategy proposed in the expert report and the assessment which includes a multidisciplinary HAS recommendations of December 2016 that followed evaluation of psychosocial status and drug and it, it would be possible to reimburse DAA fully in France. alcohol use, allowing for an integrated follow-up. Furthermore, it was decided in March 2018 that the new 5: PWID should receive individualized HCV treatment pangenotypic drugs could henceforth be delivered in phar- in a clinical setting enabling access to a macies and no longer only in hospitals. multidisciplinary team including drug and alcohol The next step will be to increase the number of pre- services, as well as psychiatric and social services, if scribing physicians, which is currently limited to hospital possible in a single location. gastroenterologists, hepatologists, and specialists of in- 6: Harm reduction information and counselling should ternal medicine and infectious diseases. To move towards be provided during HCV treatment to prevent HCV the recommendations of the expert report and to be able re-infection after a successful treatment, especially to implement the ministry’s decision, the abovementioned with PWID who exhibit ongoing risk-behaviors. treatment strategy should be able to be prescribed not 7: Following SVR, screening for HCV re-infection in only by these specialists but also by the clinicians working PWID should be performed yearly with HCV RNA. in the CSAPA and CAARUD and by general practitioners who are members of the hepatitis networks. Such a meas- This research did not receive any special grant from ure is likely to be taken in May 2018. funding agencies in the public, commercial or not-for-profit sectors. Conclusion Major decreases in prevalent HCV infections occur only Endnotes when treatment is initiated at the early stages of fibrosis, Jean-Michel Delile (coordinator), Xavier Aknine, Antoine suggesting that systematic treatment of PWID would be Bachelard, Georges Brousse, Michel Doffoel, Stéphanie beneficial. However, elimination of HCV within the next Dominguez, Juliette Foucher, Marie Jauffret-Roustide, 10 years will be difficult to achieve by treatment alone, Martine Lacoste, Pascal Mélin, Sébastien Mouveroux, even with a much-improved offer of care. The new HCV Fabrice Olivet, Brigitte Reiller, Perrine Roux, Gilles Rozsypal, Delile et al. Hepatology, Medicine and Policy (2018) 3:7 Page 7 of 9 Acknowledgements 7. Weill-Barillet L, Pillonel J, Semaille C, Léon L, Le Strat Y, Pascal X, Barin F, We wish to acknowledge all the members of the French working group Jauffret-Roustide M. Hepatitis C virus and HIV seroprevalences, (“Organization of the care and follow-up of HCV-positive drug users.”) sociodemographic characteristics, behaviors and access to syringes among who contributed to the recommendations presented in this article. All drug users, a comparison of geographical areas in France, ANRS-Coquelicot are mentioned in the manuscript: 2011 survey. Rev Epidemiol Sante Publique. 2016;64(4):301–12. Xavier Aknine, general practitioner, Gagny; Antoine Bachelard, University 8. Grebely J, Raffa JD, Lai C, Kerr T, Fischer B, Krajden M, Dore GJ, Tyndall MW. Hospital, Créteil; Georges Brousse, University Hospital, Clermont-Ferrand; Impact of hepatitis C virus infection on all-cause and liver-related mortality Michel Doffoel, University Hospital, Strasbourg; Stéphanie Dominguez, in a large community-based cohort of inner city residents. J Viral Hepat. University Hospital, Créteil; Martine Lacoste, Clémence Isaure regional 2011;18(1):32–41. Association, Toulouse; Pascal Mélin, SOS Hepatitis Association, Bagnolet; 9. Yu A, Spinelli JJ, Cook DA, Buxton JA, Krajden M. Mortality among British Sébastien Mouveroux, Aides Association, Pantin; Fabrice Olivet, Drug Columbians testing for hepatitis C antibody. BMC Public Health. 2013;13:291. Users Support group ASUD, Paris; Gilles Rozsypal, Merlet Farm (CEID), 10. Czernichow P. Hépatites B et C : mieux savoir pour mieux agir. Bull Saint-Martin-de-Laye. Epidemiol Hebd. 2016;13-14:222–3. We also thank Ray Cooke who provided editorial assistance. 11. Hepworth J, Bain T, van Driel M. Hepatitis C, mental health and equity of access to antiviral therapy: a systematic narrative review. Int J Equity Health. 2013;12(1):1–8. Authors’ contributions 12. Schaefer M, Sarkar R, Diez-Quevedo C. Management of Mental Health JMD conceived the study and drafted the manuscript. Prof VdL carried out Problems Prior to and during treatment of hepatitis C virus infection in the hepatological screening and gave treatment. MJR provided patients with drug addiction. Clin Infect Dis. 2013;57(suppl 2):S111–7. epidemiological data and helped to draft the manuscript. PR contributed epidemiological data. BR as addictologist and JF as hepatologist participated 13. Soriano V, Gallego L. Viral hepatitis: treating hepatitis C in injection drug in the integrated approach chapter. Prof DD conceived of the study with users. Nat Rev Gastroenterol Hepatol. 2013;10(10):568–9. JMD, participated in its design and coordination and helped to draft the 14. Meyer JP, Althoff AL, Altice FL. Optimizing care for HIV-infected people who manuscript. All authors read and approved the final manuscript. use drugs: evidence-based approaches to overcoming healthcare disparities. Clin Infect Dis. 2013;57(9):1309–17. 15. Martin N, Vickerman P, Foster G, Hutchinson S, Goldberg D, Hickman M. Can Ethics approval and consent to participate antiviral therapy for hepatitis C reduce the prevalence of HCV among Not applicable. injecting drug user populations ? A modeling analysis of its prevention The manuscript does not report on or involve the use of any animal or utility. J Hepatol. 2011;54:1137–44. human data or tissue, this section is not applicable to your submission. 16. Martin NK, Vickerman P, Miners A, Foster GR, Hutchinson SJ, Goldberg DJ, Hickman M. Cost-effectiveness of hepatitis C virus antiviral treatment for Competing interests injection drug user populations. Hepatology. 2012;55(1):49–57. The authors declare that they have no competing interests. 17. Ball AL. Universal access to HIV/AIDS treatment for injecting drug users: keeping the promise. Int J Drug Policy. 2007;18:241–5. 18. Martin NK, Vickerman P, Dore G, Hickman M. The HCV epidemics in key Publisher’sNote populations (including PWID, prisoners, and MSM): the use of DAAs as Springer Nature remains neutral with regard to jurisdictional claims in treatment for prevention. Curr Opin HIV AIDS. 2015;10(5):374–80. published maps and institutional affiliations. 19. Cousien A, Tran VC, Deuffic-Burban S, Jauffret-Roustide M, Mabileau G, Dhersin JS, Yazdanpanah Y. Effectiveness and cost-effectiveness of Author details interventions targeting harm reduction and chronic hepatitis C cascade of Comité d’étude et d’information sur la drogue et les addictions (CEID), 20, care in people who inject drugs; the case of France. J Viral Hepat. 2018 Apr place Pey-Berland, 33000 Bordeaux, France. Hôpital du Haut-Lévêque, 16. https://doi.org/10.1111/jvh.12919. [Epub ahead of print Pessac, France. Cermes 3 (Inserm U988/CNRS UMR 8211/EHESS/Paris Descartes University) and French National Public Health Agency, Paris, 20. 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Hepatology, Medicine and PolicySpringer Journals

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