Marie Jauffret-Roustide

A national cross-sectional study among drug-users in France: epidemiology of HCV and highlight on practical and statistical aspects of the design

BackgroundEpidemiology of HCV infection among drug users (DUs) has been widely studied. Prevalence and sociobehavioural data among DUs are therefore available in most countries but no study has taken into account in the sampling weights one important aspect of the way of life of DUs, namely that they can use one or more specialized services during the study period. In 2004–2005, we conducted a national seroepidemiologic survey of DUs, based on a random sampling design using the Generalised Weight Share Method (GWSM) and on blood testing.MethodsA cross-sectional multicenter survey was done among DUs having injected or snorted drugs at least once in their life. We conducted a two stage random survey of DUs selected to represent the diversity of drug use. The fact that DUs can use more than one structure during the study period has an impact on their inclusion probabilities. To calculate a correct sampling weight, we used the GWSM. A sociobehavioral questionnaire was administered by interviewers. Selected DUs were asked to self-collect a fingerprick blood sample on blotting paper.ResultsOf all DUs selected, 1462 (75%) accepted to participate. HCV seroprevalence was 59.8% [95% CI: 50.7–68.3]. Of DUs under 30 years, 28% were HCV seropositive. Of HCV-infected DUs, 27% were unaware of their status. In the month prior to interview, 13% of DUs shared a syringe, 38% other injection parapharnelia and 81% shared a crack pipe. In multivariate analysis, factors independently associated with HCV seropositivity were age over 30, HIV seropositivity, having ever injected drugs, opiate substitution treatment (OST), crack use, and precarious housing.ConclusionThis is the first time that blood testing combined to GWSM is applied to a DUs population, which improve the estimate of HCV prevalence. HCV seroprevalence is high, indeed by the youngest DUs. And a large proportion of DUs are not aware of their status. Our multivariate analysis identifies risk factors such as crack consumption and unstable housing.

Hepatitis C treatment as prevention of viral transmission and liver‐related morbidity in persons who inject drugs

Hepatitis C virus (HCV) seroprevalence remains high in people who inject drug (PWID) populations, often above 60%. Highly effective direct‐acting antiviral (DAA) regimens (90% efficacy) are becoming available for HCV treatment. This therapeutic revolution raises the possibility of eliminating HCV from this population. However, for this, an effective cascade of care is required. In the context of the available DAA therapies, we used a dynamic individual‐based model including a model of the PWID social network to simulate the impact of improved testing, linkage to care, and adherence to treatment, and of modified treatment recommendation on the transmission and on the morbidity of HCV in PWID in France. Under the current incidence and cascade of care, with treatment initiated at fibrosis stage ≥F2, HCV prevalence decreased from 42.8% to 24.9% (95% confidence interval: 24.8‐24.9) after 10 years. Changing treatment initiation criteria to treat from F0 was the only intervention leading to a substantial additional decrease in prevalence, which fell to 11.6% (95% CI: 11.6‐11.7) at 10 years. Combining this change with improved testing, linkage to care, and adherence to treatment decreased HCV prevalence to 7.0% (95% CI: 7.0‐7.1) at 10 years and avoided 15% (95% CI: 14‐17) and 29% (95% CI: 28‐30) of cirrhosis complications over 10 and 40 years, respectively. Conclusions: Major decreases in prevalent HCV infections occur only when treatment is initiated at early stages of fibrosis, suggesting that systematic treatment in PWID, where incidence remains high, would be beneficial. However, elimination within the 10 next years will be difficult to achieve using treatment alone, even with a highly improved cascade of care. (Hepatology 2016;63:1090–1101)

The undiagnosed chronically-infected HCV population in France. Implications for expanded testing recommendations in 2014.

Background Recent HCV therapeutic advances make effective screening crucial for potential HCV eradication. To identify the target population for a possible population-based screening strategy to complement current risk-based testing in France, we aimed to estimate the number of adults with undiagnosed chronic HCV infection and age and gender distribution at two time points: 2004 and 2014. Methods A model taking into account mortality, HCV incidence and diagnosis rates was applied to the 2004 national seroprevalence survey. Results In 2014, an estimated 74,102 individuals aged 18 to 80 were undiagnosed for chronic HCV infection (plausible interval: 64,920-83,283) compared with 100,868 [95%CI: 58,534-143,202] in 2004. Men aged 18-59 represented approximately half of the undiagnosed population in 2014. The proportion of undiagnosed individuals in 2004 (43%) varied from 21.9% to 74.1% in the 1945-1965 and 1924-1944 birth cohorts. Consequently, age and gender distributions between the chronically-infected (diagnosed and undiagnosed) and undiagnosed HCV populations were different, the 1945-1965 birth cohort representing 48.9% and 24.7%, respectively. Conclusions Many individuals were still undiagnosed in 2014 despite a marked reduction with respect to 2004. The present work contributed to the 2014 recommendation of a new French complementary screening strategy, consisting in one-time simultaneous HCV, HBV and HIV testing in men aged 18-60. Further studies are needed to assess the cost-effectiveness and feasibility of such a strategy. We also demonstrated that data on the undiagnosed HCV population are crucial to help adapt testing strategies, as the features of the chronically-infected HCV population are very distinct.

Dynamic modelling of hepatitis C virus transmission among people who inject drugs: a methodological review.

Equipment sharing among people who inject drugs (PWID) is a key risk factor in infection by hepatitis C virus (HCV). Both the effectiveness and cost–effectiveness of interventions aimed at reducing HCV transmission in this population (such as opioid substitution therapy, needle exchange programmes or improved treatment) are difficult to evaluate using field surveys. Ethical issues and complicated access to the PWID population make it difficult to gather epidemiological data. In this context, mathematical modelling of HCV transmission is a useful alternative for comparing the cost and effectiveness of various interventions. Several models have been developed in the past few years. They are often based on strong hypotheses concerning the population structure. This review presents compartmental and individual‐based models to underline their strengths and limits in the context of HCV infection among PWID. The final section discusses the main results of the papers.

Design-based inference in time-location sampling

Time-location sampling (TLS), also called time-space sampling or venue-based sampling is a sampling technique widely used in populations at high risk of infectious diseases. The principle is to reach individuals in places and at times where they gather. For example, men who have sex with men meet in gay venues at certain times of the day, and homeless people or drug users come together to take advantage of services provided to them (accommodation, care, meals). The statistical analysis of data coming from TLS surveys has been comprehensively discussed in the literature. Two issues of particular importance are the inclusion or not of sampling weights and how to deal with the frequency of venue attendance (FVA) of individuals during the course of the survey. The objective of this article is to present TLS in the context of sampling theory, to calculate sampling weights and to propose design-based inference taking into account the FVA. The properties of an estimator ignoring the FVA and of the design-based estimator are assessed and contrasted both through a simulation study and using real data from a recent cross-sectional survey conducted in France among drug users. We show that the estimators of prevalence or a total can be strongly biased if the FVA is ignored, while the design-based estimator taking FVA into account is unbiased even when declarative errors occur in the FVA.

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

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).

Limited access to HIV prevention in French prisons (ANRS PRI2DE): implications for public health and drug policy

BackgroundOverpopulation, poor hygiene and disease prevention conditions in prisons are major structural determinants of increased infectious risk within prison settings but evidence-based national and WHO guidelines provide clear indications on how to reduce this risk. We sought to estimate the level of infectious risk by measuring how French prisons adhere to national and WHO guidelines.MethodsA nationwide survey targeting the heads of medical (all French prisons) and psychiatric (26 French prisons) units was conducted using a postal questionnaire and a phone interview mainly focusing on access to prevention interventions, i.e. bleach, opioid substitution treatment (OST), HBV vaccination and post-exposure prophylaxis (PEP) for French prisoners. Two scores were built reflecting adherence to national and WHO international guidelines, ranging from 0 (no adherence) to 10 (maximum adherence) and 0 to 9 respectively.ResultsA majority (N = 113 (66%)) of the 171 prisons answered the questionnaires, representing 74% coverage (46,786 prisoners) of the French prison population: 108 were medical units and 12 were psychiatric units. Inmate access to prevention was poor. The median[IQR] score measuring adherence to national guidelines was quite low (4.5[2.5; 5.5]) but adherence to WHO guidelines was even lower 2.5[1.5; 3.5]; PEP was absent despite reported risky practices. Unsuitable OST delivery practices were frequently observed.ConclusionsA wide gap exists between HIV prevention policies and their application in prisons. Similar assessments in other countries may be needed to guide a global policy reform in prison settings. Adequate funding together with innovative interventions able to remove structural and ideological barriers to HIV prevention are now needed to motivate those in charge of prison health, to improve their working environment and to relieve French prisoners from their currently debilitating conditions.

Restrictions on access to direct-acting antivirals for people who inject drugs: The European Hep-CORE study and the role of patient groups in monitoring national HCV responses

Abstract In 2016, the World Health Organization (WHO) called for the elimination of viral hepatitis as a public health threat and established the targets of achieving an 80% reduction in new infections and a 65% reduction in deaths from the hepatitis C virus (HCV) by 2030. If European countries are to come close to reaching the WHO targets, they must squarely address the HCV prevention, testing and treatment needs of people who inject drugs (PWID). This viewpoint reports on findings from the 2016 European Hep-CORE study, which was unique in its utilisation of patient groups as a source of hepatitis policy information. We found widespread treatment restrictions affecting PWID in European countries and suggest that involving civil society stakeholders in monitoring is essential for implementing HCV treatment-as-prevention strategies as well as achieving broader viral hepatitis elimination targets.

HIV infection among persons who inject drugs: ending old epidemics and addressing new outbreaks.

Des Jarlais et al. [1] highlight how HIV transmission among persons who inject drugs (PWID) has decreased considerably since the implementation of harmreduction policies. They provide a stimulating reflection on how to end old HIV epidemics and address new outbreaks in PWID [1]. Focusing on New York, Vancouver and France, their analysis shows how localized epidemics can still spread, even in countries where HIV seroprevalence has noticeably declined. However, some of the French data used are not suitable to reliably document the epidemic’s current dynamic, and more recent data are available.

Hep-CORE: a cross-sectional study of the viral hepatitis policy environment reported by patient groups in 25 European countries in 2016 and 2017

The first World Health Organization (WHO) global health sector strategy on hepatitis B and C viruses (HBV and HCV) has called for the elimination of viral hepatitis as a major public health threat by 2030. This study assesses policies and programmes in support of elimination efforts as reported by patient groups in Europe.