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

Sweden

Marianne Alanko, Vilma Molnegren, Per Björkman,

Anders WidellDepartments of Clinical Microbiology and Infectious

Diseases University Hospital of Malmö, Sweden

The NEPs in SwedenNEP = Needle (and syringe) Exchange

ProgrammeFree 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

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

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

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

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

The Malmö NEP

Malmö280000 inhabitants, presumably 1000-1500

IVDUs

Malmö NEPRequirements: 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

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)

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

Second study, 1997-2005, focusing on the freshly recruited IVDUs (Alanko, JVH, 2010)Serology supported by Nucleic Acid Testing on HCV

New participants 1997-2005

N=1661

Without ID-numberN=454

With ID-number1207

Cohort for follow-upN=832

One blood sample only

N=351

No blood samples within

NEPN=24

1997-2005 study, baseline virus prevalence in subset providing one blood sample only (MA)

One blood sample only

N=351

HIV2 (0.6%) A-HIV+

HBV144 (41.0%) A-HBc

+

HCV258 (73.7%) A-

HCV+

1997-2005 study, baseline virus prevalence in IVDU cohort providing >2 blood samples (MA)

Cohort for follow-upN=832

HIV1 (0.12%) A-

HIV+

HBV236 (28.4%) A-

HBc +

HCV500 (60.1%) A-

HCV+

Incidence – normalized to new suceptible cases per 100 person years

Number of

susceptibles

Number of

seroconversions

Years at

risk

Seroconversions

/100 pyr

Compared to

1990–1993**

HIV 830 2 2433 0.08 0.00

HBV 588 39 1160 3.4 11.7

HCV 332 186 486 38.3 (31.5*) 26.3

*) Månsson et al, Scand J Infect Dis 32: 253-258, 2000

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

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.

The rest of this presentation will focus on HCV, as mentioned our best surrogate marker for NEP ”leakage”

Starting with baseline risk factors….

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)

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en

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60

50

40

30

20

10

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Inte v iremi

Viremi i A-HCV negativt prov senare

Viremi vid inträdet

Viremi

Time in NEP (years)

Viremia in anti-HCV negative sample at NEP enrolmentViremia in anti-HCV negative sample within NEPNo detectable viremia in anti-HCV negative sample

Number ofpersons

Figure 1. Detectable HCVviremia in last anti-HCV negative sample in 186 incident HCV infections

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0,8

0,6

0,4

0,2

0,0

03-05-censored00-02-censored97-99-censored

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Survival Functions

Time to HCV or time in NEP

Survival functions

Year of registration in NEP

Cum

Surv

ival

Fra

ctio

n of

ant

i-HC

V n

egat

ive

IDU

s

Months

No improvement in HCV incidence from 1997-2005

Quantitative retrospective HCV RNA testing in 198 seroconverters Roche Ampliprep/Taqman quantitative RNA assay Dynamic range: 15 IU/ml - 69 million IU/mlNormal test volume: 1 ml of plasma.We used 100 µl of biobanked IVDU serum diluted with 900 µl anti-HCV neg serumThus 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

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

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

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 infectionsMake a return to more normal

life/family/work possible

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

Thank You