Drug users (DUs) are at high risk for HIV and HCV infections 1. Among DUs, HCV, like HIV, is mainly transmitted through needle sharing. However, HCV (Hepatitis C Virus) is more easily transmitted than HIV because its prevalence is greater than for HIV (Human Immunodefiency Virus), it is more resistant to desiccation 23 and is also linked to the sharing of drug paraphernalia (water, filter, spoon) 45678. HCV infection can, therefore, occur after much less injection and sharing episodes 9101112. To minimize the risk of HIV and HCV, harm reduction policies have been adopted in many industrialized countries 1314151617. Many studies have studied the epidemiology and risk factors for HCV infection among DUs 18192021222324252627 and shown that harm reduction policies have had a major impact on HIV among DUs but a much more limited impact on HCV infection 10282930313233343536. HCV prevalence estimates remain high 37, over 50% in the majority of countries where data are available 38. In all these studies, prevalence and sociobehavioural data among DUs are available and useful for public health issues. So far, 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. This has an impact on their inclusion probabilities, and accordingly on estimates.

In France, most data on HIV and HCV infection among DUs come from notifications or highly selected population samples 39404142 and no prevalence estimates of HIV and HCV infection based on laboratory confirmation were available among DUs. In 2004–2005, we therefore conducted a national survey among DUs who resided in metropolitan France (the ANRS-Coquelicot study) to assess the prevalence of HIV and HCV infections based on serum testing, the frequencies of at risk practices, and the risk factors for HCV prevalence. To improve the estimate of HIV and HCV prevalences, we used a sampling design including the Generalised Weight Share Method (GWSM) described by Ardilly and Lavallee 4344, taking into account the use of specialized services by each DU during the study period.

In 2004–2005, we conducted a two stage random survey of DUs in five French large cities (Lille, Strasbourg, Paris, Bordeaux and Marseilles). Given the expected size of the sample, these five cities were chosen due to the important number of specialized structures for DUs, and the prevalence of drug use in each city. Prevalence rates of drug addiction were estimated from available data on opiate substitution treatments (OST) 31. The five cities from five different regions were also selected to represent the diversity of drug addiction (products and modes of consumption) in France. The first stage of the design was constituted of high-and low-threshold care structures for DUs and of general practitioners (GPs) and the second stage by DUs. A DU to be included in the survey was a person >18 years who had injected or snorted drugs "at least once in its life" and accepted to participate in the survey after informed consent.

Among the 2389 DUs who were invited to participate in the survey, 483 refused, 444 did not correspond to the population of interest and 1462 accepted. The participation rate was 75%. There was no significant difference between those who participated and those who did not for age, gender and by type of services. Reasons of refusals included lack of time to respond (65%), psychological or physical status judged not compatible with the completion of a questionnaire (13%), lack of interest for the study (8.5%), refusal without reason (7.8%), 4.6% of refusals were not documented and only 3 refusals were linked to a care structures' staff.

Among DUs who participated, 79% accepted to provide a fingerprick blood sample. Reasons for not providing a blood sample were obtained on a sub sample of 53 refusals and included: lack of a confined space for collecting blood or no microlancet available (24.5%), thickness of finger skin (18.9%), refusal to self use the microlancet (20.8%), no time (13.2%), psychological or physical status judged not compatible with the test (11.3%) and religious reasons (3.8%). Only 3.8% persons refused by fears to be identified and 3.8% of refusals were linked to the non restitution of the test result. In multivariate analysis, the main factors associated to refusal of blood sampling were no prior HIV and HCV testing, knowing HCV transmission routes and having been recruited outside a general medical practice.

To our knowledge this is the first national survey among DUs, enabling estimates of HIV and HCV prevalence rates and their confidence intervals, based on a random sampling design using the Generalised Weight Share Method (GWSM) and blood testing. It is also the first attempt to apply the GWSM to a public health study. This method was previously used in a demographic survey of French homeless people 43 whose relationships with support facilities are almost similar to those of DUs. Our random sampling design allowed us to make inference to the French DUs reached by specialized services and GPs, and to obtain correct confidence intervals.

The use of GWSM with blood testing is a way to obtain more valid estimates of HCV prevalence. We showed that 27% of DUs were not aware of their HCV-seropositive status, probably because they had become infected since their last test. Therefore, HCV prevalence estimates based on declarative data do not reflect the real prevalence among DUs.

Because our study targeted DUs managed in specialized centers and by GPs, it does not provide information on "hidden" populations of DUs that do not use such services 4849. Furthermore, without available precise census data on the French DUs population, no post stratification could be done. In our study, the youngest, the most socially inserted and the females DUs are less likely to use DUs specialized structures which may have biased our estimates. However, better socially inserted DUs were partly included in the study through recruitment by GPs. A declaration bias by structures of the size of the population of DUs they care for is possible to increase public funding and could impact the sampling design. However, nothing allows us to assert that certain structures had overestimated DUs' visits more than others. We made an important effort to limit such biases by securing a high confidentiality of data collection and recording. A desirability bias is also possible as in all studies of stigmatized behaviours. To limit its impact we used professional interviewers who were totally independent of the investigated structures. Interviewers were trained and followed up during field data collection through meetings to maintain homogeneity, create a reliable climate towards DUs and to limit the social desirability bias. Although cities were not chosen at random, structures were included in 5 cities all over France to reflect the diversity of drug use in France and visit days in the structures and DUs were randomly selected. There were no differences by sex, age and service between participants and those who refused participation, however, no other data was available for comparison and guarantee comparability of those who refused and participated.

Despite these limitations, we believe that using this innovative statistical approach has improved the efficiency of our study and gave more valid estimates of the HIV and HCV public health burden among DUs and associated risk factors.

In the ANRS-Coquelicot study, the HCV seroprevalence (59.8%) is more than five times greater than for HIV (10.8%) and almost all those infected by HIV were also infected with HCV which stresses the huge public health burden of both infections in this population. HCV seroprevalence did not differ significantly among the five cities included, although HIV prevalence differed significantly between Lille (1%) and Marseilles (31.5%). This finding is probably related to differences in at-risk behaviour by city: in Marseille DUs are known to inject more (83% had ever injected) than DUs from other cities (65%). In the years 1970s to 1990s, DUs from south of France (including Marseille) injected heroin much more than in the North of France (including Lille) where heroin was more often smoked which is at much lower risk of HIV transmission.

Our analysis by year of birth indicates that the French harm reduction policy, fully implemented since 1994 (SEP and OST), had probably a strong impact on HIV transmission but much less and delayed for HCV transmission. We recognize that one must be careful when establishing a link between harm reduction programmes and their differentiated impact on HIV and HCV using a cross-sectional study. However, in France and in other western countries, the decrease of HIV prevalence among DUs, although partially explained by mortality, and the small proportion of DUs among HIV patients who recently discovered their HIV status observed since the implementation of harm reduction policies strongly suggest a link with harm reduction programmes 10282930313233343536.

The high HCV seroprevalence among DUs with about 30% of those under 30 years of age affected is a finding of high public health concern. It results from a combination of several factors, including the high prevalence of HCV infection (59.8%) in the global population, the higher transmissibility of HCV compared to HIV, and difficulties for DUs to reduce further behaviors at risk of HCV infection 50. In addition to syringe and needles sharing, HCV is also transmitted by sharing drug paraphernalia (water, spoon, filter...) 478. In our study the level of drug paraphernalia sharing (38%) remains substantial, and syringe reuse (74%) is very high. Reuse of a personal syringe can also be risky for HCV transmission if the drug solution is drawn from a shared container and can be considered as an "indirect sharing". The high HCV seroprevalence before 30 years old indicates that DUs are rapidly infected after drug initiation. New and young DUs are often initiated by older peers (83% in our study) who, because they are older, are more likely to be infected with HCV 5152. Furthermore, a third of DUs (27%) are not aware of their HCV seropositive status. HCV infection often occurs early after adoption of the intravenous route 912535455. Therefore, the opportunity of HCV transmission will remain substantial without implementing new prevention strategies that target all these critical points.

Our multivariate analysis confirmed known risk factors for HCV infection, such as age, injection at least once and HIV seropositivity 235657. We also identified crack consumption and unstable housing conditions as risk factors. Social vulnerability and precarious housing conditions expose DUs to a greater risk of HCV transmission because they are dependent on others for injection, less able to anticipate the time of injection and prepare safely the necessary equipment. They may also have to inject in public places or in the homes of other DUs which favor unsafe practices and the sharing of injection equipment. However, precarious housing conditions may also be a consequence of HCV infection 585960.

The link between HCV infection and crack smoking (in the last month) can be interpreted in two ways. In France, most crack users had injected heroine in the 1980s when no harm reduction policy was in place. Alternatively, sharing of crack pipes has been shown to be a possible way to transmit HCV 46162. Glass crack pipes become very warm and break which result in cuts and lip lesions that can serve as routes for HCV transmission 636465. Therefore, this association is interesting but complex to interpret. Indeed, it is difficult to say whether the association is due to crack users injection patterns in the past, whether it is due to transmission by crack pipes, or whether former injection drug users, many of whom could be infected by HCV, have switched to non-injection use of crack to try and lower their risk of infection with other pathogens.

Although the prevalence of HCV infection was similar by gender (56% among females vs 61% in males) it does not imply similar risk factors as shown in our analysis stratified by gender. While our results by gender must be interpretated cautiously because of model unstability (wide confidence intervals of OR), in a sociological analysis done within our study, women have been shown to be highly engaged in at-risk behaviours while consuming drugs or having sex 49. Other studies have also reported differences in risk factors by gender among DUs, with females being more vulnerable than males 366676869.

In our study, questions on drug consumption and at-risk practices explored the month prior to interview. Therefore, the impact of long-term consumption and behaviours could not be assessed. It would have been useful to collect drug consumption over entire life to assess drug consumption trajectory of DUs. We chose not to include these variables in our questionnaire because the interview could not last more than 30 minutes in field conditions.

The incidence of HCV infection in the most recent cohort study of DUs varied from 2% in the Netherlands in 2005 70 to 10% in France in 2000 71, 18% in the United States in 2000–2001 72 and 42% in London in 2001 33. If most of the studies show that harm reduction policies have not yet had a perceptible impact on HCV transmission among DUs 73, a recent study in the Netherlands indicates that HCV transmission among DUs can be reduced by intense and large scale harm reduction policies combining access to SEP and opiate substitutive treatments 7074 and that it takes longer to observe a measurable impact on HCV than on HIV. In France, it is too early to document a similar impact since the harm reduction policy was implemented later than in the Netherlands.

Our study shows that HCV seroprevalence is very high (59.8%) among DUs in France. The high frequency of third-party initiation in drug injection, the persistence of at risk behaviours, the lack of awareness of HCV serostatus, and the extreme social vulnerability facilitate HCV transmission, particularly for the youngest and most recent DUs. It is therefore necessary to focus prevention strategies on avoiding starting drug injection, sharing of injection paraphernalia and own reuse, and initiation of injection for both the initiator and the initiated. Additional preventive strategies are needed for crack users and educational programmes for safer injection of injectors. It is also important to take into account the health of DUs more globally through integrated social services and to improve access to screening and treatment of HCV.

ANRS: agence nationale de recherches sur le sida et les hépatites; CI: confidence interval; DBS: dried blood spot; DU(s): drug users(s); GPs: General Practioners; GWSM: Generalised Weight Share Method; HCV: hepatitis C virus; HIV: human immunodeficiency virus; OR: Odd Ratio; PR: prevalence ratio; OST: Opiate Substitution Treatment; SEP: syringe exchange programmes

The authors declare that they have no competing interests.

All authors read and approved the final manuscript. MJR is the main investigator for this research. She designed the survey, coordinated its implementation, data collection and scientific activites, conducted the main analysis and wrote the epidemiological section of the article. YLS prepared the sampling strategy of the survey, produced weighted parameter estimates and wrote the statistical section. EC merged the biological and epidemiological data and contributed to cleaning the database and to the preliminary analysis. DT did the biological analyses for the survey. MR and GG contributed to data analysis. MQ coordinated the field survey. NR contributed to the sampling strategy of the survey. JE designed the survey with MJR. FB designed the biological part of the survey and wrote the section on biological testing. JCD supervised the whole survey design and scientific work and edited the manuscript