A hepatitis A, B, C and HIV prevalence and risk factor study in ever injecting and non-injecting drug users in Luxembourg associated with HAV and HBV immunisations

The prevalence of hepatitis C virus (HCV) infection in injecting drug users varies between regions in Europe from 40 to 90% [1]. Before 2005, data on the prevalence of hepatitis B virus (HBV) infection in IDUs were limited. Prevalence figures for Europe in 2007-08 [2] were highly variable due to differences in vaccination coverage. The positivity of the Hepatitis core antibody (anti-HBc) which indicates a contact with the viral particle reveals a hepatitis B prevalence over 40%. Limited prevalence data exist for hepatitis A (HAV) infection in the same population. Human immunodeficiency virus type 1 (HIV-1) prevalence in IDUs ranges between 0% and 21% in the European Union, although it does not exceed 5% in most Member states [3].

Prevalence of HCV among nIDUs varies in Europe between 10 and 20% [4] and remains higher than among the general population. The same prevalence trend is observed among nIDUs for HBV and HIV infections [4‐6].

Epidemiological follow-up of problem drug use in Luxembourg relies on a nation-wide multi-sector surveillance system called "RELIS". RELIS was established in 1995 and conceived on the methodological assumption that data exclusively collected from drug treatment settings may not provide an accurate picture of the problem drug-using population as it notably excludes out-of-treatment drug users who for instance have had conflicts with law enforcement bodies due to the problematic aspect of their drug use. The RELIS network includes in- and out-patient treatment centres (100% coverage), including hospitals providing detoxification treatment, national prisons and law enforcement agencies. Data collection is performed via a series of contextual protocols ("first contact", "update" or "identification" protocol), self-reported data and setting-related data (number of: contacts, syringes exchanged...). The yearly output of RELIS largely contributes to the publication of the national annual drugs report. According to RELIS data [3] a weak upward trend in HIV/IDUs self-reported prevalence has been observed from 3.5% in 1998 to 5% in 2004, and hepatitis C prevalence stood at 74% in 2004. In 1998, the first published data about Luxembourg prison [7] reported HIV and HCV prevalence in IDU prison inmates of 4.3%, respectively 37%. Among all reported new cases of HIV-1 infection in Luxembourg, few seem to occur in IDUs [4]: 6 HIV-1 infections out of 30 new cases (20%) occurred through injecting drug use in 1999 compared to only 3 out of 60 (5%) in 2004 [8].

Our study pursued three goals: i) defining the prevalence of viral hepatitis B, C and HIV in IDUs and nIDUs in Luxembourg, ii) analysing risk factors of viral infections in IDUs and iii) assessing the need and feasibility of HAV and HBV immunisations in PDUs.

Our work aims to provide a comprehensive nationwide insight into selected chronic viral infections in IDUs and non IDUs. All types of PDU care settings were included in the study and about 15% of the estimated PDU population in Luxembourg was recruited with a low participation rate of 31% following initial contact. Part of the explanation may lie within the recruitment in low-threshold services with PDUs often deferring participation and not reappearing later.

A comparison between respondents and non-respondents in this hard-to-reach population was not possible in our study. However, we gathered the most representative sample of the Luxembourg PDU population although a selection bias stands with lower participation rate in outpatients (84%) and higher ones in inpatients (100%) and prisons (99%). A cross-sectional study conducted in Luxembourg in 1999 also showed a 33.9% response rate [13]. Other limitations of the study can be detected in the recruitment method targeting exclusively the PDUs in contact with ITCs, OTCs or PCs, thereby not reaching those not in contact with such institutions. Secondly, the heterogeneity of the types of PDUs (injectors or not) attending the various settings makes the interpretation of the results somewhat uneasy. Since the initiation of the project had an action-research design, the first priority was to reach, test and treat if required as many PDUs as possible, which implies less selective recruitment criteria. Also, the questionnaire items did not allow differentiating between ever- and current injectors, which would have allowed further in-depth analysis.

Overall, HCV prevalence was 81.3% in IDUs and 19.1% in non IDUs. Those rates put Luxembourg in the upper range of HCV prevalence among IDUs in Europe [1]. Among nIDUs the rate is lower compared to Italy or Spain [5, 6], but remains much higher than the estimated HCV prevalence rate (0.5%-1%) in the general population [14].

Compared to PCs (86.3%; 95%CI: 80.2-92.3), the prevalence of HCV was lower in ITCs (75.4%; 95%CI: 64.6-86.2) and OTCs (57.3%; 95%CI: 48.8-65.8). There may be a selection bias in recruitment as outpatients showed less motivation to participate in the study by postponing their participation. Also, in prison the access to sterile material brings IDUs to be more at stake when it comes to infection risks.

Alike, Belgium [15] reported higher HCV prevalence rates in imprisoned drug injectors (76%). In the HCV multivariate analysis, being an IDU older than 25 years and being in ITC or PC rather than in OTC increased the risk (OR: 4.2) of HCVab. Consistent with other studies, each year of injection drug use increases the risk of contracting HCV by a factor of 1.14, and drug use in prison generates a risk of 3.16 fold [10, 16].

Since no viral load assays were performed in our study, we were unable to distinguish chronic active from past resolved HCV infections. Based on literature, we can estimate however that about 55-85% of seropositive had indeed an ongoing chronic infection [17]. In addition, a viral genotype assay might have added valuable information. A recent study performed in Luxembourg suggests that IDUs are 4.54 times more likely to be infected by HCV genotype 3 than other patients, even if adjusted for age and gender [14]. Genotype 3 has roughly 80% of chances of sustained response to a standard 6-month interferon/ribavirin treatment. Preliminary data now show that a shorter treatment course of only 3 months may have the same cure rate [18]. Therefore, one might speculate that offering short antiviral treatments to a large number of IDUs with genotype 3 would have the potential to reduce the transmission rate in the population by dramatically lowering the infectious reservoir.

In IDUs, HBVab prevalence was 29.1%. Again we found significantly higher HBVab prevalence in prisons (34.8%;95%CI: 26.1-43.5) compared to other settings. In IDUs, national prevalence rates for HBcAb, HBsAg and HBsAb are scarce in Europe, ranging respectively from 0.7%-64%, 2.3%-6.1% and 25%-37% [19]. Belgium reports 18% HBVab (acute/chronic infections and cured infections) in IDUs [15]. Our study shows high HBsAb (65.4%) probably due to a relatively high HBV vaccination rate in IDUs when compared to other countries [20, 21]. Also, only about 3.9% (95%CI: 1.5-6.3) of IDUs presented active HBV infection (Antigen HBs positive), leaving little room for therapeutic interventions. On the other hand, with only 46% of IDUs (95%CI: 40.0-52.2) protected by vaccination and 19.3% (95%CI: 14.5-24.2) having acquired HBV, there is clearly a need for an improved vaccination policy at an earlier stage. Among nIDUs, HBVab prevalence was 8.9%, showing a lower rate than Italy or Spain (respectively 22.8%, 20.7%) [5, 6]. In the HBV multivariate analysis, increasing age, more than 6 years' speedball career and non-Luxembourg nationality increases the risk of contracting HBV.

The results of the multivariate analysis with increasing age, more than 6 years' speedball career and non-Luxembourg nationality favouring HBV transmission are consistent with those of other studies [20, 22]. They concur with the need to improve an early stage vaccination policy and the one to target non-nationals.

Vaccinations for PDUs are recommended in all the settings wherever feasible and although no difference in HBV vaccination rates according to different settings has been observed, awareness should be further raised among physicians regarding the importance and usefulness of HBV vaccination in PDUs.

We found no case of acute HAV infection; however, 41% of PDUs were unprotected against HAV and would have benefited from immunisation.

The prevalence of HIV among IDUs was 2.5%. Again the highest prevalence was found in prison (7.7%). In the European Union, HIV prevalence in IDUs varies from 1% in the UK to 30% in Spain [23]; Neighbouring Belgium reports 3% and 4% in prisons among IDUs [15]. The lower rates for HIV infection compared to HCV might be explained by lower viral infectivity [24, 25]. Among nIDUs, HIV prevalence was 4.8% showing a higher rate than in Italy (1.6%) and Spain (2.7%) [5, 6]. This rate is also higher than the estimated 0.2% HIV infection rate in the general population of Luxembourg. Nevertheless, the highest risk of HIV contamination in Luxembourg, remains through male homosexual intercourse or heterosexual contacts [26].

Our data shows that co-infections are common. The univariate analysis in the IDU population associates gender with HBV, age with HBV and HCV, and nationality with HCV infection. Likewise findings from other studies [20, 21] showed that duration of drug use was significantly associated with an increase in HBV and HCV infections (Table 3).

Drug injectors are particularly exposed to infection risks [27, 28] as they are apt to lend or borrow paraphernalia. Cups and filters were the most commonly exchanged objects in our study, even though free of charge, sterile and ready-to-use kits for drug use are widely available in the vicinity of the main consumption spots. Sixty-five percent of drug-injecting study respondents reported discarding their used syringes in syringe exchange programmes. Worrisome, however, is that syringes are inappropriately eliminated in 23% of the cases with a syringe/needle separation occurring in 15% and needles discarded in an inadequate place in 8% of the cases. These types of behaviour result in increased infection risks for others. Cleaning or disinfection of used syringes and needles is predominantly observed in prisons. Yet, 72% use only water (which does not disinfect) for cleaning, which points out to the fact that appropriate prevention measures were not readily available in prisons. As lifestyle and consumption habits of PDUs as well as daily constraints to procure drugs rarely comply with appointments, the organisation and maintenance of medical interventions were highly challenging. As long as the treatment centres' employees and the field investigator who had established close contacts with the participants, reminded them of their appointments, about half (54.6%) of the tested PDUs saw the physicians and received immunisations where appropriate. After the 8-month inclusion period, only the physicians were active in the field in order to complete the immunisation programmes. Although the system was meticulously planned, not one additional follow-up was obtained under these conditions. One way of improvement might be rapid, point-of-care tests providing results in a few minutes and allowing immediate advice and immunisation if appropriate. However, even if completing a vaccination scheme was the ultimate goal, one has to bear in mind the concept « One dose is better than no dose » [29], which suggests that there is a protective effect even from uncompleted schemes.

In conclusion, our findings confirm that the prevalence of chronic viral infections and especially HCV is high among IDUs in Luxembourg. Also, the prevalence among nIDUs is noticeable for HBV. Therefore low- threshold opportunities for immediate testing, information on prevention, access to prevention material, immunisation and treatment if appropriate should be improved among PDUs. A syringe distribution programme for IDUs in prisons is highly suggested and has been in force in Luxembourg since the summer of 2005. Awareness should be further raised among physicians regarding the importance and usefulness of HBV/HAV vaccination in PDUs at the earliest stage of PDU. Tackling the problem of chronic viral infections in PDU is difficult, especially when it comes to gaining adherence to screening and immunisation schemes as shown in our study. In order to evaluate future trends in viral infections and effects of prevention programmes, the implementation of a continuous surveillance system for chronic viral infections in the PDU population should be considered [30, 31].