Updated Experience of a Needle-Syringe Exchange Program NEPs in Malmö, Sweden

1. Updated Experience of a Needle-Syringe Exchange Program NEPs in Malmö, Sweden Marianne Alanko, Vilma Molnegren, Per Björkman, Anders Widell Departments of Clinical Microbiology and Infectious Diseases University Hospital of Malmö, Sweden

2. The NEPs in Sweden NEP = Needle (and syringe) Exchange Programme Free exchange of used injection gear against similar number of CLEAN needles /syringes) to reduce circulation time of infected gear IVDU = Intravenous Drug User • Lund NEP started in 1986, local initiative to prevent HIV spread • Malmö started 1987, 6 mo later, also local initiative • Other projects started, but discontinued by 1989

3. The NEPs in Sweden • Major criticism and concern from “official Sweden” • Both Malmö and Lund projects were reluctantly allowed on a trial evaluation project basis • In the outside World NEPs rapidly became one cornerstone in HIV prevention • In 2007 Swedish government decided to transfer NEP permissions to local counties – so far limited response, except Helsingborg 2010, Kristianstad 2011? • Probably Stockholm will follow, in a limited way

4. Physical features of NEPs • Offer free needles and syringes, under exchange format – leading to less reuse, shorter circulation • Offer regular testing • Provide a non criminalizing environment which the IVDU can and will return to • A platform for vaccination against HAV, HBV • First, HIV prevention but also against blood borne viruses – and bacteria • And sexually transmitted diseases/ free condoms

5. Build Mental barriers against infection risks • Provide Correct and updated knowledge of the IVDU´s own infection status • Health education • Close contacts • Leaflets, • Films • Interviews for new trends and habits • Prevention against Overdose - the ultimate harm – and its management • Motivate for Methadone and Sobutex mainenance therapy participation

6. So what are the potentials of NEPs? • Beyond direct prevention – be prospective sampling platforms for unique, biological materials covering both incident and chronic infections. • Independent on clinical disease • Understanding transmission patterns - phylogeny • Test for “new” infections in high risk groups • This should lead to improved NEPs • The ultimate goals remain • long term drug freedom after detoxification • if impossible, maintenance methadone therapy • treatment of acquired infections • Return to more normal life

7. The Malmö NEP Malmö 280000 inhabitants, presumably 1000-1500 IVDUs Malmö NEP Requirements: participants > 20years and signs of ongoing injection >6000 participants since start in 1987 • Goal: Blood sampling every 3 months, sera tested for anti-HIV, HBsAg, anti-HBc, anti HCV • Sere then biobanked, traceable by Swedish 10-digit personal numbers • Next visits, retest on sero-negative markers

8. First Malmö NEP study 1990-1993 (Månsson, Widell, SCJID, 2000) • The whole cohort was studied by serological markers (anti-HIV, HBsAg, anti-HBc, anti-HCV • Number of patients= 515 • Results • Low baseline prev of HIV, high of HBV and highest of HCV • No new HIV cases in cohort spanning 4 years • High incidences of HBV (11.7/100 /pyr) • High incidence of HCV (26.3/100 pyr)

9. Conclusions of first NEP study 1990-1993 (Månsson, Widell, SCJID, 2000) • HIV did not spread – like in Stockholm • But background prevalence was low • HBV incidence was high – but could subsequently be influenced by vaccination • HCV incidence even higher – with no vaccine available – HCV incidence reflects “leakage” in NEP • HCV good surrogate marker in non exposed, but 60 % already exposed • NEPs can be improved

10. New participants 1997-2005 N=1661 Without ID-number N=454 With ID-number 1207 Cohort for follow-up N=832 One blood sample only N=351 No blood samples within NEP N=24 Second study, 1997-2005, focusing on the freshly recruited IVDUs (Alanko, JVH, 2010)Serology supported by Nucleic Acid Testing on HCV

11. One blood sample only N=351 HIV 2 (0.6%) A-HIV+ HBV 144 (41.0%) A-HBc + HCV 258 (73.7%) A-HCV+ 1997-2005 study, baseline virus prevalence in subset providing one blood sample only (MA)

12. Cohort for follow-up N=832 HIV 1 (0.12%) A-HIV+ HBV 236 (28.4%) A-HBc + HCV 500 (60.1%) A-HCV+ 1997-2005 study, baseline virus prevalence in IVDU cohort providing >2 blood samples (MA)

13. Incidence – normalized to new suceptible cases per 100 person years *) Månsson et al, Scand J Infect Dis 32: 253-258, 2000

14. HBV and vaccination in 1997-2005 • In the longitudinal cohort, 588 persons were susceptible to HBV at entry. • 351 (60%) received at least three doses of vaccine, and protective levels of anti-HBs were achieved in 321 (91%). • HBV infection occurred in 39 participants (21 with documented HBsAg and anti-HBc, 18 with anti-HBc only) in a median interval between NEP enrolment and anti-HBc seroconversion was 17

15. HBV incidence and vaccination • Nineteen (48%) of the 39 incident HBV cases had begun vaccination; 11 had obtained only one dose and two had received two. • Six of the subjects with incident HBV were fully vaccinated (3 doses) but had never achieved anti-HBs > 10mIU/mL. • No incident case of HBV occurred in vaccine responders. • Five of the incident HBV cases developed chronic HBV infection.

16. The rest of this presentation will focus on HCV, as mentioned our best surrogate marker for NEP ”leakage” Starting with baseline risk factors….

18. Confounder of HCV incidence in the NEP – IVDUs in HCV window phase when enrolling? • HCV RNA PCR (Roche Taqman) revealed viremia in 67 of the last anti-HCV negative blood samples. • 37 participants had registered in the window phase (> women). • Adjusted incidence 31.5/100 pyr (compared to 38/100 pyr by antibody detection)

19. Figure 1. Detectable HCVviremia in last anti-HCV negative sample in 186 incident HCV infections Viremia in anti-HCV negative sample at NEP enrolment Viremia in anti-HCV negative sample within NEP No detectable viremia in anti-HCV negative sample Number of persons Time in NEP (years)

20. No improvement in HCV incidence from 1997-2005 Fraction of anti-HCV negative IDUs Months

21. Quantitative retrospective HCV RNA testing in 198 seroconverters • Roche Ampliprep/Taqman quantitative RNA assay • Dynamic range: 15 IU/ml - 69 million IU/ml • Normal test volume: 1 ml of plasma. • We used 100 µl of biobanked IVDU serum diluted with 900 µl anti-HCV neg serum • Thus a lower linear detection limit < 150 IU/ml • The last anti-HCV negative serum, • The first anti-HCV positive serum, • Span between samples normally 3-6 months, • A serum drawn approximately 1 year later

22. Ongoing specifically biobank related work • This prospectively collected serum biobank of silently seroconverting IVDUs is valuable for further studies, like • Viral genotype, NS5B phylogenetics including Baysian • Mixed HCV genotype infection - Luminex • Neutralization (HCVpp, HCVcc) • Other viruses HTLV, Parv4, XMRV, HEV?? • Bringing the NEP biobank studies from retrospective risk analysis into truly PROSPECTIVE • And remember – we have patients PIN

23. Crash plan for incident HCV Prospective, early identification of incident HCV • HCV Ag on anti-HCV negative NEP participants • HCV RNA and phylogenetic analysis • Questionnaire at each sampling • Deep interview early in each incident case “Recover Black Box” • Deepen our understanding how much paraphernalia (utensils beyond needles and syringes) contribute to transmission. • Optimal needle/syringe coverage – opening times • If noting is done, vulnerability for HIV remains

24. Summary – our overall NEP goals for NEP partipants • Survival • Stop further transmission of HIV and other viruses • Initiate long term drug freedom after detoxification • If impossible, transfer to maintenance methadone therapy • Offer treatment of acquired infections • Make a return to more normal life/family/work possible

25. And for HCV specifically • Study the natural course of infection in our NEP participants acquiring HCV since 90% of incident HCV infections are subclinical and acute “icteric, clinical hepatitis C may not be representative for the overall pattern in hepatitis C • Whatever pattern that leads to chronic viremia – these are the patients who will be the bulk of our patients

26. Thank You