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Best Practice/Intervention: MacArthur GJ. et al. (2014) Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness. International Journal of Drug Policy, 25(1):34-52. Date of Review: June 14, 2015 Reviewer(s): Christine Hu Part A Category: Basic Science Clinical Science Public Health/Epidemiology Social Science Programmatic Review Best Practice/Intervention: Focus: Hepatitis C Hepatitis C/HIV Other: Level: Group Individual Other: Target Population: people who inject drugs (PWID) Setting: Health care setting/Clinic Home Other: Country of Origin: United Kingdom Language: English French Other: Part B YES NO N/A COMMENTS Is the best practice/intervention a meta-analysis or primary research? Please go to Comments section. Systematic review of reviews to assess the effectiveness of harm reduction interventions in relation to HIV, HCV transmission and injecting risk behavior. - Synthesize latest review-level evidence regarding the effectiveness of: needle and syringe programs, provision of injection paraphernalia, opiate substitution treatment, information, education and counseling, and supervised injecting facilities Criteria Grid Best Practices and Interventions for the Prevention and Awareness of Hepatitis C

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Page 1: Criteria Grid Best Practices and Interventions for the ... … · Best Practices and Interventions for the Prevention and Awareness of Hepatitis C . The best practice/intervention

Best Practice/Intervention: MacArthur GJ. et al. (2014) Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness. International Journal of Drug Policy, 25(1):34-52.

Date of Review: June 14, 2015

Reviewer(s): Christine Hu

Part A

Category: Basic Science Clinical Science Public Health/Epidemiology

Social Science Programmatic Review

Best Practice/Intervention: Focus: Hepatitis C Hepatitis C/HIV Other:

Level: Group Individual Other:

Target Population: people who inject drugs (PWID)

Setting: Health care setting/Clinic Home Other:

Country of Origin: United Kingdom

Language: English French Other:

Part B

YES NO N/A COMMENTS

Is the best practice/intervention a meta-analysis or primary research? Please go to Comments section.

Systematic review of reviews to assess the effectiveness of harm reduction interventions in relation to HIV, HCV transmission and injecting risk behavior.

- Synthesize latest review-level evidence regarding the effectiveness of: needle and syringe programs, provision of injection paraphernalia, opiate substitution treatment, information, education and counseling, and supervised injecting facilities

Criteria Grid Best Practices and Interventions for the Prevention and Awareness of Hepatitis C

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The best practice/intervention shows evidence of “scale up” ability

This article is an update and extension of previous published review of review on evidence for effectiveness of needle/syringe program in the prevention of HIV and HCV among PWID

The best practice/intervention shows evidence of transferability

The best practice/intervention shows evidence of adaptation

Do the methodology/results described allow the reviewer(s) to assess the generalizability of the results?

YES NO N/A COMMENTS

Are the best practices/methodology/results described applicable in developed countries?

Results of this review of review are applicable to people who inject drugs worldwide.

Are the best practices/methodology/results described applicable in developing countries?

The best practice/intervention has utilized a program evaluation process

Consultation and feedback with community has taken place

The best practice/intervention is sensitive to gender issues

Review articles included in this review may have done analysis of gender difference and various population difference in HCV and HIV transmission among PWID

The best practice/intervention is sensitive to multicultural and marginalized populations

The best practice/intervention is easily accessed/available electronically

Purchase/journal subscription required for access from

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http://www.sciencedirect.com/

Is there evidence of a cost effective analysis? If so, what does the evidence say? Please go to Comments section

How is the best practice/intervention funded? Please go to Comments section

The study was funded by the European Centre of Disease Prevention and Control (ECDC) and the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).

Is the best practice/intervention dependent on external funds?

Other relevant criteria:

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International Journal of Drug Policy 25 (2014) 34– 52

Contents lists available at ScienceDirect

International Journal of Drug Policy

journa l h o me page: www.elsev ier .com/ locate /drugpo

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nterventions to prevent HIV and Hepatitis C in people who injectrugs: A review of reviews to assess evidence of effectiveness

eorgina J. MacArthura,∗, Eva van Velzenb, Norah Palmateerc, Jo Kimberd,nastasia Pharrise, Vivian Hopef,g, Avril Taylorh, Kirsty Royc, Esther Aspinall i,avid Goldbergc, Tim Rhodes f, Dagmar Hedrich j, Mika Salminene,atthew Hickmana, Sharon J. Hutchinsonc,h

School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UKNHS Sutton and Merton/London KSS Specialty School of Public Health, UKHealth Protection Scotland, Glasgow, UKUniversity of New South Wales, Sydney, AustraliaEuropean Centre for Disease Prevention and Control, Solna, SwedenCentre for Research on Drugs and Health Behaviour, London School of Hygiene and Tropical Medicine, London, UKHealth Protection Services, Health Protection Agency, London, UKUniversity of the West of Scotland, Paisley, Scotland, UKDepartment of Mathematics and Statistics, University of Strathclyde, Glasgow, UKEuropean Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal

r t i c l e i n f o

rticle history:eceived 27 June 2012eceived in revised form 25 June 2013ccepted 3 July 2013

eywords:epatitis CIVarm reductioneople who inject drugseview

a b s t r a c t

Background: Injecting drug use is a major risk factor for the acquisition and transmission of HIV andHepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is criticalto reduce ongoing transmission, morbidity and mortality.Methods: A review of reviews was undertaken involving systematic literature searches of Medline,Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000–2011) to identify English languagereviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCVtransmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes(NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, educa-tion and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into ‘core’ or‘supplementary’ using critical appraisal criteria, and the strength of review-level evidence was assessed.Results: Twelve core and thirteen supplementary reviews were included. From these reviews we identi-fied: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission,insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence inrelation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV trans-mission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, theprovision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reduc-ing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or

HCV transmission.Conclusion: Review-level evidence indicates that harm reduction interventions can reduce IRB, with evi-dence strongest for OST and NSP. However, there is comparatively little review-level evidence regardingthe effectiveness of these interventions in preventing HCV transmission among PWID. Further studies areneeded to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction

e HIV

interventions to minimis

∗ Corresponding author. Tel.: +44 0 117 928 7295; fax: +44 0 117 331 2094.E-mail address: [email protected] (G.J. MacArthur).

955-3959/$ – see front matter © 2013 Elsevier B.V. All rights reserved.ttp://dx.doi.org/10.1016/j.drugpo.2013.07.001

and HCV transmission among PWID.© 2013 Elsevier B.V. All rights reserved.

Introduction

Recent estimates suggest that there may be between 11 and 21

million people who inject drugs (PWID) worldwide (Mathers et al.,2008). Through the sharing of drug injection equipment, these indi-viduals are at increased risk of acquiring blood-borne viruses suchas HIV and Hepatitis C virus (HCV), and thus substantial morbidity
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nd mortality. It is estimated that approximately 3 million (range.8–6.6 million) PWID might be living with HIV (Mathers et al.,008), whilst 10 million (range 6.0–15.2 million) might have HCVNelson et al., 2011). Country-specific estimates of HIV prevalencemongst PWID are generally below 20%, but estimated prevalences at least 40% in Spain, parts of Eastern Europe, Asia, Latin Americand Sub-Saharan Africa (Mathers et al., 2008; Wiessing et al., 2008).stimates of HCV prevalence among PWID are generally greaterhan 40%, and many countries have reported prevalence estimatesreater than 60% (Nelson et al., 2011; Wiessing et al., 2011).

Prevention of primary infection with HIV and HCV is criti-al to reduce long-term morbidity in PWID. There is evidence toupport the effectiveness of harm reduction interventions suchs needle and syringe programmes (NSP) and opiate substitutionreatment (OST) in reducing HIV transmission (Degenhardt et al.,010; Kimber et al., 2010; Palmateer et al., 2008; Tilson et al., 2007),nd recent studies indicate that the combination of OST and NSPan significantly reduce HCV and HIV incidence (Hagan, Pouget,

Des Jarlais, 2011; Turner et al., 2011; Van Den Berg, Smit, Vanrussel, Coutinho, & Prins, 2007). However, evidence relating tohe effectiveness of NSP alone in relation to HCV transmission isess clear (Hagan et al., 2011; Palmateer et al., 2010) and there isomparatively little evidence regarding the effectiveness of otherarm reduction interventions such as supervised injecting facil-

ties (SIFs) and behavioural interventions in relation to HIV andCV transmission (Hedrich, 2004; Kerr, Kimber, Debeck, & Wood,007; Sacks-Davis, Horyniak, Grebely, & Hellard, 2011). To date,ew reviews have systematically examined evidence on the impactf the full range of harm reduction interventions in relation to bothIV and HCV transmission among PWID.

We previously published a review of reviews (RoR) (includ-ng reviews published up to March 2007) on evidence for theffectiveness of NSP in the prevention of HIV and HCV amongWID (Palmateer et al., 2010). In this paper, we update and extendhe previously published RoR to collate and synthesise the latesteview-level evidence regarding the effectiveness of the follow-ng harm reduction interventions: NSP, OST, information, educationnd counselling (IEC) and SIFs in preventing injecting risk behaviourIRB), HIV and HCV transmission among PWID. Related reviewsave informed European guidance for the prevention of infectiousiseases among PWID, published jointly by the European Centreor Disease Prevention and Control (ECDC) and the European Mon-toring Centre for Drugs and Drug Addiction (EMCDDA) (Europeanentre for Disease Prevention, 2011).

ethods

We used a review of reviews (RoR) approach: given thencreasing number of reviews of effectiveness of public healthnterventions in the literature, the RoR aims to bring togethervidence from reviews of the effectiveness of public health inter-entions, rather than undertaking a systematic review of therimary literature itself.

The methodology has been described elsewhere (Kelly et al.,002; Palmateer et al., 2010). Briefly, the RoR entails: a systematicearch of the literature for published reviews; selection and criticalppraisal of the reviews; and synthesis of the findings into anvidence briefing, including summary evidence statements (Ellist al., 2003) (Table 1).

Studies were included if they were a systematic review, syn-hesis, meta-analysis, or literature review that considered the

ffectiveness of interventions in relation to the prevention of HIV,CV or IRB. The interventions considered were: NSP and models of

ts delivery (e.g. vending machines, pharmacies); the provision ofterile drug preparation equipment (including the provision of foil,

al of Drug Policy 25 (2014) 34– 52 35

in terms of stimulating the transition from injecting to smoking);IEC; OST; and SIFs. The outcomes considered were: HIV prevalenceor incidence; HCV prevalence or incidence; and self-reportedIRB (which included the borrowing, lending or re-use of nee-dles/syringes or other drug preparation equipment; and injectingfrequency). For OST, drug-related risk – assessed using tools suchas the risk assessment battery and HIV risk-taking behaviour scale(Navaline, Snider, & Petro, 1994; Ward, Darke, & Hall, 1990) – wasalso included as an IRB-related outcome.

Studies were included if they were published in the Englishlanguage between January 2000 and March 2011. Studies relatingto the distribution of foil were included if they were publishedbetween 2007 and March 2011, owing to the fact that this inter-vention has been implemented more recently. Reviews wereexcluded if they had considered only the sexual transmission ofHIV or HCV, or had considered interventions delivered exclusivelyin the prison setting.

Systematic searches were carried out using the CochraneLibrary, EMBASE, Medline, CINAHL and PsychINFO. IBSS wassearched to identify reviews relating to all topics covered in thestudy except drug treatment; searches for studies relating to drugtreatment were carried out at a different site. We also searched forgrey literature published by key international agencies, such as theECDC, the EMCDDA, the National Institute on Drug Abuse, the USInstitute of Medicine, the United Nations Office on Drug Control andPrevention, and the World Health Organization. Search strategiescombined text words and MESH terms to maximise the retrieval ofrelevant studies.

Abstracts of identified papers were first screened by onereviewer for relevance. Thereafter, the full-text articles werescreened by two reviewers for relevance and the selected paperswere critically appraised by two reviewers using a tool developedby the Health Development Agency (Kelly et al., 2002). This toolconsiders the strength of the methods used in the reviews includingthe identification of relevant literature, the quality of the appraisalprocess and the appropriateness of the review’s conclusions. Usingthis tool, reviews were categorised into either high-quality ‘core’reviews, which formed the basis of evidence used to assess effec-tiveness of interventions, or ‘supplementary’ reviews, which werenot considered to be of sufficient quality to rely on the authors’ con-clusions but potentially provided information on primary papersto complement the core reviews. This approach to appraisal andclassification of reviews has been described in detail elsewhere(Palmateer et al., 2010).

From each review, we extracted information on the authors’assessment of the evidence and the design and findings of rel-evant primary studies. The level of evidence in support of, ordiscounting, the effectiveness of an intervention was classified as‘sufficient’, ‘tentative’, ‘insufficient’ or ‘no’ review-level evidence,using a framework (previously developed and adopted) basedon the design and findings of the primary studies included inreviews, and concluding statements made by core review authors(Table 1) (Ellis et al., 2003; Palmateer et al., 2010). Using thisapproach, studies with longitudinal and case-control designs areconsidered more robust, whilst those with cross-sectional or eco-logical designs are considered to be weaker (Palmateer et al.,2010).

Results

A total of 1827 papers were identified in relation to NSP, the

provision of sterile drug preparation equipment, IEC, SIFs, and theprovision of foil; and 787 titles were identified in relation to OST.After removal of duplicates, screening of abstracts and full texts,and critical appraisal of relevant papers, twelve core reviews and
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36 G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52

Table 1Types of evidence statements and the level of evidence required to support each statement.

Evidence statement Level of evidence

Sufficient review-level evidence to either support ordiscount the effectiveness of an intervention

• Clear and consistent statement from one or more core reviews based on multiple robust studies, or• Consistent evidence across multiple robust studies within one or more core reviews, in the absence of aclear and consistent statement in the review(s)

Tentative review-level evidence to either support ordiscount the effectiveness of an intervention

• A tentative statement from one or more core reviews based on consistent evidence from a small numberof robust studies or multiple weaker studies, or• Consistent evidence from a small number of robust studies or multiple weaker studies within one ormore core reviews, in the absence of a clear and consistent statement in the review(s), or• Conflicting evidence from one or more core reviews, with the stronger evidence weighted towards oneside (either supporting or discounting effectiveness) and a plausible reason for the conflict, or• Consistent evidence from multiple robust studies within one or more supplementary reviews, in theabsence of a core review

Insufficient review-level evidence to either support ordiscount the effectiveness of an intervention

• A statement of insufficient evidence from a core review, or• Insufficient evidence to either support or discount the effectiveness of an intervention (either becausethere is too little evidence or the evidence is too weak), in the absence of a clear and consistent statementof evidence from a core review(s), or• Anything less than consistent evidence from multiple robust studies within one or more supplementaryreviews

No review-level evidence • No core or supplementary reviews of the topic identified, possibly due to a lack of primary studies

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odified from Ellis et al. (2003). Here, longitudinal cohort and case-control desross-sectional designs were considered to be weaker studies.

hirteen supplementary reviews were identified in relation to all ofhe harm reduction interventions (Fig. 1).

eedle and syringe provision (NSP)

Three core reviews (Gibson, Flynn, & Perales, 2001; Tilson et al.,007; Wodak & Cooney, 2004) and three supplementary reviews

A. Selec�on of pa per s rela�ng to needle and syringe progra mmes, the provision of s terile drug prepara�on equipment (including foil); informa�on, educa�on and counselling; and supervised injec�on facili�es (2000-2011).

Abst racts and �tles iden �fied (n = 1827)

Duplicates excluded (n = 251)

Remaini ng ab stracts scre ened for relevan ce (n = 1576)

Abst racts exc luded as not relevant

(n = 1406)

Remaini ng full text papers sc reened by tw o re viewers

(n = 170)

Papers excluded as not relevant (n = 149 )

Full text papers cri�cally ap prai sed by tw o re viewers

(n = 21)

Supple menta ry re views (n = 11 )

Core reviews (n = 10)

Cochrane (n=62)CINAHL (n=515)EMBASE (n=675)Medline (n=382)PsychINFO & IBSS (n=163)Grey literatur e (n=30)

ig. 1. Studies identified in the review of reviews. (A) Selection of papers relating to neeincluding foil); information, education and counselling; and supervised injection facilit2000–2011) (*) One core and one supplementary review identified here in relation to OSTquipment, IEC and SIFs.

ere considered to be robust studies, while ecological, serial cross-sectional and

(Hong & Li, 2009; Nacopoulos, Lewtas, & Ousterhout, 2010; Wright& Tompkins, 2006) were identified in relation to NSP (Table 2).

Effects on injecting risk behaviour

The three core reviews included 43 primary studies betweenthem, 26 of which appeared in at least two of the reviews (Avants

B. Selec�on of pa per s rela�ng to opiat e su bs� tu�on tre atment (2000 -2011 )

* One core and on e su pplementary re view iden� fied her e in re la�on to OST were al so iden�fied in the sea rch for NSP, the prov ision of ster ile dru g prepa ra�on e quipment , IEC and SIFs.

Abstracts and �tles iden�fied n = (787 )

Dupli cates e xcluded (n = 108)

Remaini ng ab stracts scre ened for relevan ce (n = 67 9)

Abst racts exc luded as not relevant(n =618)

Remaining full text papers screened by tw o re viewers

(n = 61)

Papers excl ude d as not relevant (n =55)

Full text papers cri�cally ap prai sed by tw o re viewers

(n = 6)

Cochrane (n=10)CINAHL (n=95)EMBASE (n=449)Medline (n=218)PsychINFO (n =8)Grey lite ratur e (n=7)

Core reviews* (n = 3)

Supple menta ry re views*(n = 3)

dle and syringe programmes, the provision of sterile drug preparation equipmenties (2000–2011). (B) Selection of papers relating to opiate substitution treatment

were also identified in the search for NSP, the provision of sterile drug preparation

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G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52 37

Table 2Summary of core and supplementary reviews of the effectiveness of NSP, alternative access to needles and syringes, and the provision of sterile drug preparation equipment.

Author and date Title Dates covered Intervention covered inreview

Type of review Number of relevantprimary studiesincluded in thereview, by outcome

Gibson et al. (2001) Effectiveness of syringe exchangeprograms in reducing HIV riskbehaviour and HIV seroconversionamong PWID

Up to 1999 NSP Core 3 HCV6 HIV23 IRB

Gillies et al. (2010) The provision of non-needle/syringe drug injectingparaphernalia in the primaryprevention of HCV among PWID: asystematic review

Up to Feb 2010 Injection drug useequipment (specified asdrug cookers, filters and/orwater)

Core 1 HCV0 HIV13 IRB

Hong and Li (2009) HIV/AIDS behaviouralinterventions in China: a literaturereview and recommendation forfuture research

Up to April 2008 NSP (among other harmreduction interventions)

Supplementary 2 HIV/HCV1 HCV

Islam andConigrave (2007)

Assessing the role of syringedispensing machines and mobilevan outlets in reachinghard-to-reach and high-risk groupsof injecting drug users (PWID): areview

Not specified Alternative access to NSP:vending machines

Supplementary 1 IRB

Islam, Wodak et al.(2008)

The effectiveness and safety ofsyringe vending machines as acomponent of needle syringeprogrammes in communitysettings

Up to 2008 Alternative access to NSP:community vendingmachines

Supplementary 1 IRB

Jones et al. (2010) Optimal provision of needle andsyringe programmes for injectingdrug users: A systematic review

Up to January 2008 Alternative access to NSP:pharmacy NSP, fixed NSP,outreach NSP, vendingmachines; not prison based

Core 2 HCV/HIV9 IRB

Nacopoulos et al.(2010)

Syringe exchange programs:Impact on injection drug users andthe role of the pharmacist from aU.S. perspective

Up to 2010 NSP Supplementary 6 HCV/HIV9 IRB

Tilson et al. (2007) Preventing HIV infection amonginjecting drug users in high-riskcountries: an assessment of theevidence

Up to Jan 2006 NSP; alternative access toNSP (pharmacy NSP andvending machines); andinjection drug useequipment (among otherharm reductioninterventions)

Core 6 HCV

12 HIV24 IRB

Wodak and Cooney(2004)

Effectiveness of sterile needle andsyringe programming in reducingHIV/AIDS among injecting drugusers

Up to 2002 NSP (among other harmreduction interventions);prison NSP; alternativeaccess to NSP (pharmacyNSP and vendingmachines)

Core 1 HCV10 HIV28 IRB

Wright andTompkins (2006)

A review of the evidence for theeffectiveness of primary

Up to end 2002 NSP (among other harmreduction interventions)

Supplementary 9 HCV

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prevention interventions forHepatitis C among injecting drugusers

t al., 1999; Avants et al., 2004; Baker et al., 1993; Ball et al., 1998;atki et al., 1989; Bluthenthal et al., 1998; Bluthenthal et al., 2000;rooner et al., 1998; Calsyn et al., 1992; Colon et al., 2009; Cox et al.,000; Deren et al., 1995; Des Jarlais et al., 2000, 1994; Donoghoet al., 1992; Donoghoe et al., 1989; Frischer and Elliott, 1993;ibson et al., 2002; Gleghorn et al., 1998; Guydish et al., 1998,995; Hagan et al., 1993; Hart et al., 1989; Hartgers et al., 1989,992; Heimer et al., 2002; Heimer et al., 1998; Supplementaryable 1). Supplementary reviews are not described in relationo IRB since the evidence included in these reviews did not alterhe evidence statement derived based on studies identified inore reviews (see Table 1). The majority of studies (i.e. thirty nineut of forty three studies) included in the core reviews reported

positive finding, i.e. a reduction in IRB associated with NSPTable 3; Huo and Ouellet, 2007; Iguchi, 1998; Keene et al., 1993;ipke et al., 1997; Klee and Morris, 1995; Kwiatkowski and Booth,001; Lamden et al., 1998; Latkin et al., 2003; Lott et al., 2006;

Magura et al., 1991; Mandell et al., 1994; Meandzija et al., 1994;Monterroso et al., 2000; Oliver et al., 1994; Paone et al., 1994;Peak et al., 1995; Power and Nozhkina, 2002; Robles et al., 1993;Sarkar et al., 2003; Schoenbaum et al., 1996; Sears et al., 2001a;Sears et al., 2001b; Shore et al., 1996; Simpson et al., 1995; Steinet al., 2002; Sterk et al., 2003; Strang et al., 2000; van Ameijdenand Coutinho, 1998; van Ameijden et al., 1994; van den Hoek et al.,1989; Vazirian et al., 2005; Vertefeuille et al., 2000; Vlahov et al.,1997; Watters et al., 1994; Supplementary Table 1).

Tilson et al. (2007) included fourteen prospective studies thatfound that participation in multi-component harm reduction pro-grams, including NSP, resulted in reductions in self-reported needlesharing (Supplementary Table 1). However, the authors acknowl-

edged limitations of reliance of self-reported measures in suchstudies. Wodak and Cooney (2004) included twenty eight stud-ies, twenty four of which reported positive findings. One additionalstudy in this review reported negative findings and three reported
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38 G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52

Table 3Summary of evidence used to generate evidence statements for each intervention and outcome measure.

Intervention Outcome Statements from core reviews Summary of findings from primarystudiesa

Evidence Statement

Provision of needles/syringes and other injecting equipmentb

(1) Needle andsyringeprogrammes (NSP)

IRB Tilson et al. (2007) provides a clearstatement of evidence in support of NSP

43 studies identified in core reviews:39 positive (20 COH, 1 EC, 18 CS)

Sufficient evidence to support theeffectiveness of NSP in reducing IRB

Wodak and Cooney (2004) does notprovide a statement of evidence

1 negative (1 CS)3 no association (1 COH, 2 CS)

Gibson (2001) provides a clearstatement of evidence in support of NSPbased on consistent evidence frommultiple robust studies

HIV Tilson et al. (2007) provides a tentativestatement of evidence in support of NSP

16 studies identified in core reviews:10 positive (2 COH, 4 EC, 4 CS)

Tentative evidence to support theeffectiveness of NSP in preventing HIV

Gibson (2001) and Wodak and Cooney(2004) both provide a clear statement ofevidence in support of NSP, butconflicting with the primary studiesreviewed

2 negative (2 COH)4 no association (2 COH, 2 CC)

HCV Tilson et al. (2007) provides a tentativestatement of evidence discounting theeffects of NSP

17 studies identified in core andsupplementary reviews:9 positive (1 CC, 6 CS, 2 EC)

Insufficient evidence to either supportor discount the effectiveness of NSP inpreventing HCV

Gibson (2001) and Wodak and Cooney(2004) do not provide statements ofevidence

2 negative (2 COH)6 no association (3 COH, 3 CS)

(2) Alternativeaccess to needlesand syringes:(a) Pharmacy

IRB Jones et al. (2010) did not provide aclear statement of evidence relating toeffectiveness

13 studies identified in core reviews:8 positive (8 CS)2 negative (2 CS)

Tentative evidence to supporteffectiveness of pharmacy access toneedles/syringes in reducing IRB

Tilson et al. (2007) provides a tentativestatement of evidence in support ofpharmacy NSP based on a small numberof studies

3 no association (1 RCT, 2 CS)

Wodak and Cooney (2004) provides atentative evidence statementsupporting pharmacy NSP

HIV Jones et al. (2010) provides a statementof insufficient or incoherent evidence

4 studies identified in core reviews:4 positive (4 CS)

Insufficient evidence to either supportor discount the effectiveness ofpharmacy access to needles/syringes inpreventing HIV

Wodak and Cooney (2004) provides atentative evidence statementsupporting pharmacy NSP butconflicting with evidence from primarystudies included

HCV No reviews identified No review-level evidence to support ordiscount effectiveness

(b) Vendingmachines

IRB Jones et al. (2010) provides a statementof insufficient evidence

3 studies identified in core andsupplementary reviews:

Insufficient evidence to either supportor discount the effectiveness ofvending machine access toneedles/syringes in reducing IRB

Tilson et al. (2007) provides a statementof insufficient evidence

1 positive (1 CS)2 no association (2 CS)

Wodak and Cooney (2004) provides astatement of evidence in support ofvending machines but conflicting withevidence from the primary studiesincluded

HIV Jones et al. (2010) does not provide anevidence statement

1 study identified in core reviews:1 no association (1 CS)

Insufficient evidence to either supportor discount the effectiveness ofvending machine access toneedles/syringes in preventing HIV

Tilson et al. (2007) does not provide anevidence statementWodak and Cooney (2004) provides astatement of evidence in support ofvending machines but conflicting withevidence from the primary studiesincluded

HCV No core reviews identified No studies identified in either core orsupplementary reviews

No review-level evidence

(c) Mobile vans IRB No core reviews identified 1 study identified in core review:1 negative (1 CS)

No review-level evidence

HIV Jones et al. (2010) does not provide astatement of evidence

1 study identified in core review:1 negative (1 CS)

Insufficient evidence to either supportor discount the effectiveness of mobilevan access to needles/syringes inpreventing HIV

HCV No core reviews identified No studies identified in either core orsupplementary reviews

No review-level evidence

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G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52 39

Table 3 (Continued)

Intervention Outcome Statements from core reviews Summary of findings from primarystudiesa

Evidence Statement

(3) Provision ofdrug preparationequipment

IRB Gillies et al. (2010) provides a tentativestatement of evidence in support of theprovision of sterile injectingparaphernalia

15 studies identified in core reviews:10 positive (6 COH, 4 CS)5 no association (2 COH, 3 CS)

Tentative evidence to support theeffectiveness of drug preparationequipment provision in reducing IRB

Tilson et al. (2007) do not provide astatement of evidence

HIV No core reviews identified No studies identified in either core orsupplementary reviews

No review-level evidence

HCV Gillies et al. (2010) do not provide astatement of evidence

1 study identified in core review:1 positive (1 CS)

Insufficient evidence to either supportor discount the effectiveness of drugpreparation equipment provision inpreventing HCV

Drug dependence treatmentAgonistpharmacologicaltreatment (i.e. OST)

IRB Gowing et al. (2008) provides astatement of evidence in support ofOST

35 studies identified in core reviews inrelation to:(a) injecting frequency:22 positive (3 RCT, 16 COH, 3 CS)(b) sharing of injecting equipment:16 positive (4 RCT, 8 COH, 4 CS)3 no association (1 COH, 2 CS)(c) drug-related risk:6 positive (1 RCT, 3 COH, 2CS)1 no association (1 RCT)c

Sufficient evidence to support theeffectiveness of OST in reducing IRB

Tilson et al. (2007) provides astatement of evidence in support ofOSTSorensen and Copeland (2000) providea statement of evidence in support ofOST

HIV Gowing et al. (2008) provides astatement of evidence in support ofeffectiveness of OST

8 studies identified in core reviews:5 positive (4 COH, 1 CC)3 no seroconversions observed (2 RCT,1 CS)

Sufficient evidence to support theeffectiveness of OST in preventing HIV

Tilson et al. (2007) provides a tentativestatement of evidence in support ofcontinuous OSTSorensen and Copeland (2000) providea statement of evidence in support ofOST

HCV No core reviews identified 12 studies identified in supplementaryreviews:4 positive (1 MA, 2 COH, 1 CC)8 no association (8 COH)

Tentative evidence to support theeffectiveness of OST in preventing HCV

Information, education and counselling (IEC)IEC IRB Medley et al. (2009) provides a

tentative statement of evidence insupport of peer educationinterventions.

28 studies identified in core reviews:18 positive (7 RCT, 10 COH, 1CS)10 no association (8 RCT, 2 CS)

Tentative evidence to support theeffectiveness of outreach whichincludes IEC in reducing IRB.

Herbst et al. (2007) do not provide astatement of evidenceTilson et al. (2007) provides a tentativestatement of evidence in support ofoutreach and educationNeedle et al. (2005) provides astatement of evidence in support ofcommunity-based outreachPrendergast et al. (2001) provides atentative statement of evidence insupport of IEC delivered within a drugtreatment programCopenhaver et al. (2006) provides astatement of evidence in support ofbehavioural interventions

HIV Tilson et al. (2007) does not provide astatement of evidence

3 studies identified in core andsupplementary reviews:3 positive (1 COH, 1 CS, 1 EC)

Insufficient evidence to either supportor discount the effectiveness of IEC inpreventing HIVNeedle et al. (2005) provides a

tentative statement of evidence insupport of community based outreach

HCV No core reviews identified 1 study identified in a supplementaryreview:1 positive (1 CS)

Insufficient evidence to either supportor discount the effectiveness of IEC inpreventing HCV

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40 G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52

Table 3 (Continued)

Intervention Outcome Statements from core reviews Summary of findings from primarystudiesa

Evidence Statement

Supervised drug consumptionSupervisedinjecting facilities(SIFs)

IRB Tilson et al. (2007) provides statementthat evidence, while encouraging, isinsufficient

7 studies identified in core andsupplementary reviews:4 positive (2 COH, 2 CS) 3 no association(3 CS) [6 further studies document thatclients’ report of positive changes totheir injecting practices can beattributed to SIF]

Tentative evidence to support theeffectiveness of SIFs in reducing IRB

HIV Tilson et al. (2007) does not provide anevidence statement

1 study identified in core andsupplementary reviews:1 no association (1 CS)

Insufficient evidence to either supportor discount the effectiveness of SIFs inpreventing HIV

HCV Tilson et al. (2007) does not provide anevidence statement

1 study identified in core andsupplementary reviews:1 no association (1 CS)

Insufficient evidence to either supportor discount the effectiveness of SIFs inpreventing HCV

a Findings of primary studies were extracted from reviews. A “positive” finding refers to a reduction in the stated outcome associated with the intervention, while a“negative” finding refers to an increase in the stated outcome associated with the intervention, and “no association” refers to no change in the outcome, or a change that didnot reach statistical significance, associated with the intervention. Robust studies refer to meta-analyses (MA), randomised controlled trials (RCT), as well as longitudinalc l (EC)

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ohort (COH) and case-control (CC) designs, while weaker studies refer to ecologicab The provision of foil is not included in the table because no reviews were identic Note that some studies reported data relating to more than one of these IRB ou

ndeterminate findings. Gibson et al. (2001) identified a furtherwo studies (Broadhead, van Hulst, & Heckathorn, 1999; Hagan,es Jarlais, & Friedman, 1994) that were suggestive of a protectiveffect of NSP (Supplementary Table 1). Overall, the majority of stud-es reported positive associations. Thus, given consistent evidencecross multiple robust studies, and strong statements of evidenceupporting NSP from two core reviews, we concluded that there isufficient review-level evidence of effectiveness in relation to IRBTable 3).

IV transmissionAlthough IRB can be viewed as a proxy for risk of HCV

nd HIV transmission, the primary studies included in the coreeviews (Gibson et al., 2001; Tilson et al., 2007; Wodak & Cooney,004) report mixed findings regarding the impact of NSP on HIV

ncidence. Among the sixteen studies included in core reviewsSupplementary Table 1), ten reported reduced HIV incidence asso-iated with NSP participation whilst four studies of robust designeported null findings (Table 3). Two prospective studies reportedn increased risk of HIV transmission associated with NSP (Bruneau,ranco, & Lamothe, 1997; Bruneau et al., 1997; Strathdee, Patrick,urrie et al., 1997). However, Tilson et al. (2007) acknowledgedhat these findings might relate to: individuals that use NSPseing at higher risk of HIV infection or having higher baseline HIVrevalence; the extent of provision of needles/syringes not beingufficient to reduce risky injecting practices; and the possibility thathose classed as ‘non-users’ of NSPs might be able to access cleaneedles/syringes from other sources, such as pharmacies. Tilsont al. (2007) also acknowledged that HIV prevalence has decreasedince those studies were published whilst NSP access has increased.

Overall, the primary studies with the most rigorous designseported mixed findings with an equal number of cohort studieseporting positive, null and negative associations (Table 3). Thereas greater consistency in findings among ecological studies, but

hese were regarded as having a weaker design. Thus, based ononsistent evidence from less robust primary studies and a ten-ative statement from one core review (Tilson et al., 2007), weoncluded that there is tentative review-level evidence to sup-ort the effectiveness of NSP in reducing HIV transmission amongWID.

CV transmissionIn relation to HCV incidence, the three core reviews (Gibson

t al., 2001; Tilson et al., 2007; Wodak & Cooney, 2004) identified

, serial cross-sectional and cross-sectional (CS) designs.

s.

seven studies between them, whilst supplementary reviews (Hong& Li, 2009; Nacopoulos et al., 2010; Wright & Tompkins, 2006) iden-tified an additional ten studies, three of which were identified inthe two more recent supplementary reviews (Supplementary Table2). Primary studies with stronger study designs (cohort and case-control studies) included in the core and supplementary reviewsshowed mixed findings: three found no association between NSPand HCV seroconversion (Hagan et al., 1999; Holtzman et al.,2009; van Ameijden, van den Hoek, Mientjes, & Coutinho, 1993),two found a negative association (Mansson, Moestrup, Nordenfelt,& Widell, 2000; Patrick et al., 2001), and one found a positiveassociation (Hagan, Jarlais, Friedman, Purchase, & Alter, 1995).Positive associations (i.e. a reduction in HCV seroconversions asso-ciated with NSP) were mainly reported by weaker primary studiesusing ecological or cross-sectional design (Des Jarlais et al., 2005;Goldberg, Cameron, & McMenamin, 1998; Goldberg et al., 2001;Hutchinson et al., 2002; MacDonald et al., 2000; Neaigus et al.,2008; Smyth, Keenan, & O’Connor, 1999; Somaini et al., 2000;Taylor et al., 2000; Wu et al., 2007). As such, based on an absenceof clear statements from core reviews, and inconsistent evidencefrom studies identified in both core and supplementary reviews,we found that there is insufficient review-level evidence to supportor discount the effectiveness of NSP in reducing HCV transmission(Table 3).

Delivery of NSPWe identified three core reviews (Jones, Pickering, Sumnall,

McVeigh, & Bellis, 2010; Tilson et al., 2007; Wodak & Cooney, 2004)and two supplementary reviews (Islam & Conigrave, 2007; Islam,Stern, Conigrave, & Wodak, 2008a; Islam, Wodak, & Conigrave,2008b) that included evidence relating to NSP delivery (Table 2).

Pharmacy-based access

Injecting risk behaviourThree core reviews (Jones et al., 2010; Tilson et al., 2007; Wodak

& Cooney, 2004) included thirteen studies, eight of which reportedpositive findings in relation to pharmacy-delivered NSP and IRB(Supplementary Table 3). However, twelve of these studies hadweaker study designs (Table 3; Supplementary Table 4).

Wodak and Cooney (2004) included six studies that reportedreductions in IRB associated with access to needles/syringes viapharmacies (Calsyn, Saxon, Freeman, & Whittaker, 1991; Gleghorn,Jones, Doherty, Celentano, & Vlahov, 1995; Groseclose et al., 1995;

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ngold & Ingold, 1989; Nelson et al., 1991; Richard, Mosier, &tkinson, 2002) but were cross-sectional in design; whilst onedditional cross-sectional study identified by Tilson et al. (2007)eported reduced syringe sharing following liberalisation of lawsllowing syringe sale from pharmacies in New York (Pouget et al.,005).

The most recent review (Jones et al., 2010) included six addi-ional studies: one RCT (Fisher, Fenaughty, Cagle, & Wells, 2003)xamined differences in injecting frequency between one groupf PWID that attended a pharmacy where needles/syringes wereold and another group that attended an NSP (or that used NSP andharmacy). All participants reduced injection frequency over timeith no difference between the groups. Five cross-sectional stud-

es were also included, two of which found a negative associationBluthenthal et al., 2004; Rhodes et al., 2004); two of which reportedo difference in IRB associated with pharmacy distribution or other

orms of distribution (Khoshnood, Blankenship, Pollack, Roan, &ltice, 2000; Obadia, Feroni, Perrin, Vlahov, & Moatti, 1999), andne of which reported significant reductions in IRB as NSP provi-ion increased, with greater likelihood of sharing among those notccessing needles/syringes via a pharmacy (Singer, Himmelgreen,eeks, Radda, & Martinez, 1997). Given tentative statements from

wo core reviews, and the large amount of evidence from studies ofeaker design, we concluded that there is tentative review-level

vidence that pharmacy access to NSP is at least as effective asedicated NSP in reducing self-reported injecting risk behaviourTable 3).

IV transmissionIn relation to HIV transmission, two of the core reviews (Jones

t al., 2010; Wodak & Cooney, 2004) included four studies relat-ng to HIV incidence (Table 3; Supplementary Table 4): one serialross-sectional (Hunter, Donoghoe, Stimson, Rhodes, & Chalmers,995) and three cross-sectional studies (Miller, Tyndall, Spittal,i, & Palepu, 2002; Nelson et al., 1991; Singer et al., 1997) whicheported lower HIV prevalence among those with ready access toterile syringes via pharmacies; among PWID who used pharmaciesather than other types of NSP; or associated with time periodsf increased access to needles/syringes via NSP and pharmacies.wo additional studies were referred to by Wodak and Cooney2004) in light of their contribution to the evidence base, whichighlighted low HIV prevalence rates associated with availabilityf pharmacy distribution of needles/syringes (De Jong, Tsagarelli, &chouten, 1999; Des Jarlais et al., 1995). However, in light of a state-ent of insufficient evidence from one core review, and a tentative

tatement from a second core review; as well as the small num-er of studies using weaker designs, we concluded that there is

nsufficient review-level evidence to draw conclusions around thempact of access to NSP via pharmacies in relation to HIV incidenceTable 3).

CV transmissionWe did not identify any reviews which assessed the impact of

harmacy NSPs in relation to HCV incidence.

ending machines

njecting risk behaviourThe most recent core review (Jones et al., 2010) included a

ross-sectional study which reported no difference in the reportedharing of needles among PWID who were primary users of vend-ng machines compared to PWID who were primary users of NSP

r pharmacy NSPs, although those who primarily used vendingachines were less likely to report sharing of injection parapher-

alia compared to those who used other sources (Obadia et al.,999). Two core reviews (Tilson et al., 2007; Wodak & Cooney,

al of Drug Policy 25 (2014) 34– 52 41

2004) included a cross-sectional pilot study of vending machines ina German prison (Heinemann & Gross, 2001); although the reviewauthors’ conclusions were slightly different, both inferred a pos-itive finding. Lastly, a supplementary review which specificallyassessed the effectiveness of vending machines (Islam, Stern et al.,2008; Islam, Wodak et al., 2008) included an additional study whichreported that needle sharing did not differ between individualswho used vending machines compared to those who used NSPor pharmacy NSP (Islam, Stern et al., 2008; Islam, Wodak et al.,2008). Given the lack of primary evidence included in both the coreand supplementary reviews, we concluded that there is insufficientreview-level evidence to support or discount the effectiveness ofneedle/syringe vending machines in reducing IRB (Table 3).

HIV transmissionTwo core reviews (Jones et al., 2010; Wodak & Cooney, 2004)

identified one cross-sectional study (Obadia et al., 1999), whichreported a reduced likelihood of HIV seropositivity among thosewho primarily used vending machines, although this was not sta-tistically significant after adjustment. Thus there was insufficientreview-level evidence to support or discount effectiveness of vend-ing machines in relation to HIV transmission (Table 3).

HCV transmissionNo reviews were identified that assessed the effects of vending

machines on HCV incidence.

Outreach NSP (mobile vans)

Injecting risk behaviourNo reviews were identified that examined the impact of out-

reach NSP in relation to IRB.

HIV transmissionOne core review (Jones et al., 2010) included one cross-sectional

study (Miller et al., 2002b), which indicated that PWID whoobtained needles/syringes via fixed site NSP and mobile vans hadhigher HIV prevalence compared to those using pharmacies. How-ever, overall, there is currently insufficient evidence to support ordiscount the effectiveness of the provision of NSP via outreach inrelation to HIV incidence.

HCV transmissionNo reviews were identified that examined the impact of out-

reach NSP in relation to IRB or HCV incidence.

The provision of sterile drug preparation equipmentFor the purposes of this review, drug preparation equipment

or paraphernalia is defined as equipment for injecting or prepar-ing drugs other than needles or syringes. Two core reviews (Gillieset al., 2010; Tilson et al., 2007) assessed evidence regarding theeffectiveness of the provision of injecting paraphernalia.

Injecting risk behaviourIn relation to IRB, ten out of fifteen primary studies identified

in the core reviews, including six cohort studies and four cross-sectional studies, reported positive findings, whilst five studiesreported no association (Supplementary Tables 5 and 6). The mostrecent core review (Gillies et al., 2010) included thirteen studies:nine of these studies reported positive findings and four reportednull findings. The authors tentatively concluded that ‘current evi-dence suggests that attendance at NSP providing sterile injecting

paraphernalia may be associated with reduced sharing of non-needle/syringe injecting paraphernalia’.

Tilson et al. (2007) identified two studies included by Gillieset al. (2010) (Hagan & Thiede, 2000; Longshore, Bluthenthal, &

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tein, 2001) and a further two cohort studies, one of which reportedositive findings (Ouellet, Huo, & Bailey, 2004), whilst the otherHuo, Bailey, Garfein, & Ouellet, 2005) reported no associationetween use of NSP (assumed to provide drug preparation equip-ent although this was not explicitly stated) and the sharing of

uch equipment. Given consistent evidence from a small numberf robust studies and a tentative statement of evidence from a coreeview, we concluded that there is tentative review-level evidenceo support the effectiveness of the provision of injecting parapher-alia in reducing IRB (Table 3).

IV transmissionNo reviews examined the impact of provision of sterile drug

reparation equipment in relation to HIV transmission.

CV transmissionOne core review (Gillies et al., 2010) assessed the impact of

roviding sterile drug preparation equipment in relation to HCVncidence. This review included only a single cross-sectional studyMorissette et al., 2007) that reported positive findings; thus, weoncluded that there is insufficient evidence regarding the impactf sterile drug preparation equipment provision in relation to HCVransmission (Table 3).

rovision of foil to stimulate route transition

We did not find any reviews relating to the provision of foil totimulate route transition, i.e. from injecting to smoking drugs. Thiss unsurprising given that the provision of foil is a relatively recentntervention thus primary studies might not yet be published orncluded in reviews.

piate substitution treatment (OST)

njecting risk behaviourThree core reviews (Gowing, Farrell, Bornemann, Sullivan, & Ali,

008; Sorensen & Copeland, 2000; Tilson et al., 2007) were iden-ified in relation to IRB (Table 4). Supplementary reviews are notescribed in relation to IRB, since evidence from these reviews didot alter the evidence statement based on the studies identified inore reviews.

As for NSP, many more studies of OST focused on IRB outcomesompared to HIV or HCV incidence. A total of thirty-five studiesere identified in the three core reviews that related to shar-

ng needles/syringes or injection frequency (Supplementary Table). As shown in Table 3, twenty-two studies related to injectingrequency, nineteen to sharing of needles/syringes, and seven torug-related risk.

The majority of studies reported positive findings and usedobust study designs (Table 3). Tilson et al. (2007) and Gowingt al. (2008) together identified thirteen studies that assessed: therevalence of injecting drug use before and after OST; frequency of

njecting at baseline and follow up; or the proportion and frequencyf injecting. All of the studies reported a significant decrease inRB between baseline and follow-up, although studies varied withespect to the duration of follow-up (3–12 months) and measure-ent of frequency of injecting drug use. Nine additional studies

eported by Sorensen and Copeland (2000) reported positive effectsf OST in relation to prevalence and frequency of injecting (Supple-entary Table 7).In relation to needle/syringe sharing, eight of nine studies iden-

ified by Gowing et al. (2008) and Tilson et al. (2007) reported

eductions in the sharing of needles and syringes between base-ine and follow up (Camacho, Bartholomew, Joe, Cloud, & Simpson,996; Chatham, Hiller, Rowan-Szal, Joe, & Simpson, 1999; Dolant al., 2003; Gossop, Marsden, Stewart, & Rolfe, 2000; Grella, Anglin,

al of Drug Policy 25 (2014) 34– 52

Rawson, Crowley, & Hasson, 1996; Margolin, Avants, Warburton,Hawkins, & Shi, 2003; Schroeder, Epstein, Umbricht, & Preston,2006; Teesson et al., 2006) whilst one cohort study reported noassociation (King, Kidorf, Stoller, & Brooner, 2000). Eight of anadditional ten studies identified by Sorensen and Copeland (2000)reported positive findings (Caplehorn & Ross, 1995; Greenfield,Bigelow, & Brooner, 1995; Klee, Faugier, Hayes, & Morris, 1991;Longshore, Hsieh, Danila, & Anglin, 1993; Magura, Kang, Nwakeze,& Demsky, 1998; Rhoades, Creson, Elk, Schmitz, & Grabowski,1998; Saxon, Calsyn, & Jackson, 1994; Stark, Muller, Bienzle, &Guggenmoos-Holzmann, 1996) and two cross-sectional studiesreported no association (Baker, Kochan, Dixon, Wodak, & Heather,1995; Calsyn et al., 1991).

Lastly, seven studies included in two core reviews (Gowing et al.,2008; Tilson et al., 2007) reported impacts of OST on risk scores,for which a higher score indicates a higher level of risk behaviour.Four studies (Abbott, Moore, Weller, & Delaney, 1998; Avants,Margolin, Kosten, Rounsaville, & Schottenfeld, 1998; Chatham et al.,1999; Marsch, Bickel, Badger, & Jacobs, 2005) reported signifi-cant decreases in HIV risk behaviour scores before and after MMT;one study reported no significant difference in mean risk scoresbetween baseline and 6-month follow up (Sees et al., 2000); andtwo studies reported significantly lower mean scores in those cur-rently receiving MMT compared to those not in treatment (Bakeret al., 1995; Mark et al., 2006).

In light of primary evidence and statements of evidence fromcore reviews in support of OST, we concluded that there is sufficientevidence to support effectiveness of OST in reducing IRB.

HIV transmissionThe three core reviews (Gowing et al., 2008; Sorensen &

Copeland, 2000; Tilson et al., 2007) included evidence relating toHIV from eight studies, seven of which had more robust studydesigns. Three cohort studies demonstrated reduced odds of HIVseroconversion among PWID in continuous OST (Metzger et al.,1993; Moss et al., 1994; Williams, McNelly, Williams, & D’Aquila,1992). Lower dose of methadone and more time spent out of OSTwas reported to be associated with higher risk of HIV transmissionin a cohort study and case-control study (Hartel & Schoenbaum,1998; Serpelloni et al., 1994), and a cross-sectional study reportedthat no PWID receiving OST over the long-term had seroconverted(Novick et al., 1990). In two further studies, there were no sero-conversions among participants of an RCT comparing methadonedosage of 50 mg vs. 80 mg over a six month period (Rhoades et al.,1998) and no seroconversions among participants of an RCT ofprison-based MMT versus waitlist controls, although this was in thecontext of low HIV prevalence and a four-month follow up period(Dolan et al., 2003). Given supportive statements of evidence in corereviews and evidence from multiple robust studies, we concludedthat there is sufficient review-level evidence to conclude that OSTis effective in reducing HIV seroconversion (Table 3).

HCV transmissionFewer robust reviews were identified regarding effectiveness of

OST in relation to HCV transmission. No core reviews assessed theimpact of OST in relation to HCV incidence, but two supplemen-tary reviews were identified (MacArthur & Hickman, 2011; Wright& Tompkins, 2006) which included relevant studies. AlthoughMacArthur and Hickman (2011) was principally a RoR, it alsoincluded a review of more recent primary studies relevant to OSTand HCV transmission.

Together the two supplementary reviews included twelve stud-

ies: one meta-analysis, ten cohort studies and a case-control study.Wright and Tompkins (2006) identified six studies: a case-controlstudy (Rezza et al., 1996) which reported lower HCV incidence asso-ciated with methadone treatment; a cohort study (Thiede, Hagan, &
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G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52 43

Table 4Summary of reviews of the effectiveness of opiate substitution treatment (OST).

Author and date Title Dates covered Intervention covered inreview

Type of review Number of relevantprimary studiesincluded in thereview, by outcome

Degenhardt et al.(2010)

Prevention of HIV infection for peoplewho inject drugs: why individual,structural, and combinationapproaches are needed

Up to 2009 OST (among other harmreduction interventionsincluding antagonistpharmacotherapy)

Supplementary 2 HIV

Gowing et al.(2008)

Substitution treatment of injectionopioid users for prevention of HIVinfection

Up to July 2003 OST Core 5 HIV 24 IRB

MacArthur andHickman (2011)

Evidence for the effectiveness ofinterventions to prevent infectionsamong people who inject drugs Part 2:Drug treatment for preventinghepatitis C, HIV and injecting riskbehaviour

2000–2010 OST Supplementary 11 HIV 12 HCV 48IRB

Sorensen andCopeland (2000)

Drug use treatment as an HIVprevention strategy: a review

1988–1998 OST (among other types ofdrug use treatment, e.g.residential treatment)

Core 6 HIV 19 IRB

Tilson et al. (2007) Preventing HIV infection amonginjecting drug users in high-riskcountries: an assessment of theevidence

Up to January 2006 OST (among other harmreduction interventions)

Core 4 HIV 21 IRB

Wright andTompkins (2006)

A review of the evidence foreffectiveness of primary prevention

Up to April 2003 OST (among other harmreduction interventions)

Supplementary 6 HCV

Mior(eedSewptt

csPisarinnNsPaDsr(

cfieo

interventions for hepatitis C amonginjecting drug users.

urrill, 2000) which reported a non-significant reduction in HCVncidence among those in treatment compared to those who areut of treatment or who have left treatment; one cohort study thateported no decrease in annual HCV incidence associated with MMTin combination with NSP) over a four year period (van Ameijdent al., 1993); and three cohort studies which reported no differ-nce in HCV incidence among those in or out of MMT (Chamot,e Saussure, Hirschel, Deglon, & Perrin, 1992; Crofts, Nigro, Oman,tevenson, & Sherman, 1997; Selvey, Denton, & Plant, 1997). How-ver, the authors highlighted that the dose of OST used in studiesas unclear, with only one study reporting mean dose, raising theossibility that under-dosing of OST might have influenced effec-iveness. Moreover, the authors highlighted that PWID may presento treatment services in later years, after HCV has been contracted.

MacArthur and Hickman (2011) included a further fiveommunity-based primary studies and a meta-analysis of six UKtudies. One cohort study reported lower HCV incidence amongWID in treatment for seven to twelve months but not among thosen treatment for up to six months (Craine et al., 2009); one cohorttudy reported that MMT in the past 6 months was protectivegainst HCV infection (Miller et al., 2004); and a third cohort studyeported lower incidence among PWID in continuous compared tonterrupted OST although the difference was not statistically sig-ificant (Hallinan, Byrne, & Dore, 2004). One cohort study reportedo difference in risk of HCV infection among PWID recruited fromSP or OST programmes (Maher et al., 2006) and lastly a cohort

tudy demonstrated reduced risk of HCV seroconversion amongWID with full participation in harm reduction, i.e. OST and NSP,lthough this was not the case when MMT was provided alone (Vanen Berg et al., 2007). Critically, however, a pooling of data from UK

tudies demonstrated that OST alone was associated with reducedisk of HCV seroconversion in unadjusted and adjusted analysesTurner et al., 2011).

Overall, therefore, whilst a number of studies reported no asso-

iation between OST and NSP, four robust studies reported positivendings, one of which is a pooled analysis that provides strongvidence of effectiveness using a robust study design. In lightf other statements of insufficient review-level evidence in our

review being based on one or fewer robust studies, but tentativestatements being based on a small number of robust studies (or alarger number of weaker studies), we considered that the evidenceis more consistent with the latter. We thus conclude that there istentative review-level evidence to support the effectiveness of OSTin reducing HCV transmission (Table 3).

Information, education and counselling (IEC) and outreach

Six core reviews (Copenhaver, Johnson, Lee, Harman, & Carey,2006; Herbst et al., 2007; Needle et al., 2005; Prendergast, Urada,& Podus, 2001; Tilson et al., 2007) and two supplementary reviews(Coyle, Needle, & Normand, 1998; Hong & Li, 2009) were identifiedthat were relevant to effectiveness of IEC in relation to IRB, HIV orHCV transmission (Table 5). We describe studies included only inthese reviews since evidence from supplementary reviews did notalter the evidence statement.

Injecting risk behaviourAll six core reviews considered the impact of IEC on IRB, five

of which provided tentative or conclusive evidence statementsin support of effectiveness of IEC in reducing IRB (Table 3). Thecore reviews included twenty-eight studies. Eighteen studies werepositive (seventeen of which had robust study designs), and tenshowed no association (eight of which had robust study designs)(Table 3; Supplementary Table 8).

One core review (Copenhaver et al., 2006) reported findingsof a meta-analysis of randomised studies relating to education,condom use and self-management skills, and drug and sex-relatedrisk reduction. The study included twelve studies relating to IRB(Supplementary Table 8) and demonstrated that the inclusion ofIEC alongside other interventions was associated with significantreductions in drug use, although no significant reductions wereevident in the sharing of needles or equipment. The authors

highlighted that the latter finding might be related to comparisonwith control conditions that were similar to the interventionsbeing evaluated; a statement of evidence in support of behaviouralinterventions was nevertheless provided (Table 3).
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44 G.J. MacArthur et al. / International Journal of Drug Policy 25 (2014) 34– 52

Table 5Summary of reviews of the effectiveness of information, education, and counselling (IEC).

Author and date Title Dates covered Intervention covered inreview

Type of review Number of relevantprimary studiesincluded in thereview, by outcome

Copenhaver et al. (2006) Behavioural HIV risk reductionamong people who injectdrugs: Meta-analytic evidenceof efficacy

Up to Mar 2004 IEC (RCTs only) Core 12 IRB

Coyle et al. (1998) Outreach-based HIVprevention for injecting drugusers: a review of publishedoutcome data

Not specified IEC, Outreach Supplementary 20 IRB

Herbst et al. (2007) A systematic review andmeta-analysis of behaviouralinterventions to reduce HIVrisk behaviours of Hispanics inthe United States and PuertoRico

1988 to Dec 2005 IEC, Outreach (Latinopopulations only)

Core 3 IRB

Hong and Li (2009) HIV/AIDS behaviouralinterventions in China: aliterature review andrecommendation for futureresearch

Up to April 2008 HIV behaviouralinterventions (amongother interventions likeNSP and MMT)

Supplementary 1 HIV/HCV 2 IRB

Medley et al. (2009) Effectiveness of peer educationinterventions for HIVprevention in developingcountries: a systematic reviewand meta-analysis

Up to November2006

Peer education indeveloping countries (inc‘upper-middle incomecountries’)

Core 4 IRB

Needle et al. (2005) Effectiveness ofcommunity-based outreach inpreventing HIV/AIDS amonginjecting drug users

Not specified IEC, Outreach Core 2 HIV 4 IRB

Prendergast et al. (2001) Meta-analysis of HIV riskreduction interventions withindrug use treatment programs

1985 to 1998 IEC Core 2 IRB

Tilson et al. (2007) Preventing HIV infectionamong injecting drug users in

Up to Jan 2006 IEC, Outreach Core 1 HIV 4 IRB

aFB2aICcfi

tbtDPrai(toTba

&1

high-risk countries: anassessment of the evidence

Herbst et al. (2007) conducted a systematic review and meta-nalysis of studies in Latino populations in the United States.our studies assessed the impact of IEC on IRB (Castro & Tafoya-arazza, 1997; Colon, Robles, Freeman, & Matos, 1993; Robles et al.,004; Schilling, Fernando, Fontdevila, & El-Bassel, 2000). The meta-nalysis reported no significant effect of interventions includingEC and/or outreach in relation to needle sharing (OR 0.92, 95%I 0.81–1.04), but a significant effect on odds of sharing cotton orookers (OR 0.73, 95% CI 0.63–0.85). However, the impact of con-ounders was not explored owing to the small number of studiesncluded and the authors did not include a statement of evidence.

Prendergast et al. (2001) included two randomised controlledrials that examined the impact of counselling, discussion, skillsuilding, and demonstration of condom use and syringe disinfec-ion which demonstrated no association with IRB (Gibson, Lovelle-rache, Young, Hudes, & Sorensen, 1999; Sorensen et al., 1994).rendergast et al. (2001) also conducted a meta-analysis of HIVisk reduction interventions within drug treatment programmes,ll of which included IEC. The study pooled data from nine stud-es and demonstrated a beneficial effect on ‘risk reduction skills’mean difference 0.62, 95% CI 0.45–0.79) but not ‘injection prac-ices’ (mean difference 0.04, 95% CI −0.14–0.22), although theseutcomes were not precisely defined (Prendergast et al., 2001).he authors concluded that IEC ‘targeted specifically at HIV riskehaviours delivered within a drug treatment program can have

n impact over and above that produced by drug treatment alone’.

Tilson et al. (2007) included four studies (Colon, Sahai, Robles, Matos, 1995; Chen & Liao, 2005; Kumar, Mudaliar, & Daniels,998; Neaigus et al., 1990) and cited two reviews (Coyle et al., 1998;

Needle et al., 2005) and gave a tentative statement of evidence insupport of IEC. However, the authors highlighted that secular trendscould account for the changes observed in IRB and noted the dif-ficulty in assessing the impact of individual interventions whenseveral are implemented simultaneously.

One additional core review (Needle et al., 2005) was an updateof an earlier review (Coyle et al., 1998) and thus only includedstudies published after 1998. Three additional cohort studies wereincluded (Broadhead et al., 1998; Latkin, 1998; Wiebel et al.,1996), all of which reported a reduction in HIV-related riskbehaviour associated with outreach, and the authors concludedthat community-based outreach enables PWID to reduce the shar-ing of syringes or other drug preparation equipment.

Lastly, a recent systematic review and meta-analysis regardingthe effectiveness of peer education interventions (Medley,Kennedy, O’Reilly, & Sweat, 2009) included four studies (two cohortstudies and two cross-sectional studies), three of which reporteda statistically significant reduction in the sharing of drug injectionequipment (including needles/syringes, rinse water and/or cook-ers) (Broadhead et al., 2006; Hammett et al., 2006; Sergeyev et al.,1999) and one of which reported a non-significant reduction in nee-dle sharing (Li, Luo, & Yang, 2001). The meta-analysis identified asignificant reduction in equipment sharing after the implementa-tion of the interventions (OR 0.37, 95% CI 0.20–0.67) and the authorsconcluded that ‘peer education interventions were associated with

. . . and reduced equipment sharing among PWID’ (Medley et al.,2009).

Based on clear and tentative statements supporting the effec-tiveness of IEC in five core reviews, which base their conclusions

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n multiple weaker studies, we concluded that there is tentativeeview-level evidence to support the effectiveness of IEC, particu-arly in outreach settings, in reducing IRB in PWID (Table 3).

IV transmissionTwo core reviews considered evidence relating to HIV trans-

ission (Needle et al., 2005; Tilson et al., 2007), which identifiedwo relevant studies (Des Jarlais et al., 1998; Wiebel et al., 1996),hilst a supplementary review (Hong & Li, 2009) identified a

urther cross-sectional study (Wu et al., 2007) (Tables 3 and 5).ne prospective study of a street-based outreach intervention tar-eting social networks among HIV-negative PWID demonstrated

decline in HIV incidence over the four year follow up periodWiebel et al., 1996), whilst the other demonstrated that outreachas associated with maintained low HIV prevalence in several

ities, although it was acknowledged that the impacts of outreachould not be separated from the other interventions (Des Jarlaist al., 1998). Wu et al. (2007) reported that rates of HIV infectionere lower in communities receiving outreach whilst HIV rates

ither remained the same or increased in control communities,nd HIV incidence was significantly lower among PWID in onerovince of two where the intervention was implemented.

Needle et al. (2005) concluded that ‘community-basedutreach. . .provides credible risk reduction information and theeans for behaviour change to enable PWID populations to reduce

rug use, to reduce reuse of syringes and other drug injectingquipment. . .’ and that ‘reducing risk behaviours greatly reduces

IV transmission.’ Overall, however, in light of a lack of clear state-ents from core reviews and the small number of relevant primary

tudies, we concluded that there is insufficient review-level evi-ence to either support or discount the effectiveness of IEC and/orutreach in preventing HIV transmission.

able 6ummary of reviews of the effectiveness of supervised injecting facilities (SIFs).

Author and date Title Dates covered Ir

Dolan et al. (2000) Drug consumptionfacilities in Europe and theestablishment ofsupervised injectingcentres in Australia

Up to 2000 (no datesspecified in paper)

Df

Hedrich (2004) European report on drugconsumption rooms

Up to end 2003 Sc

Kerr et al. (2007) The role of safer injectionfacilities in the response toHIV/AIDS among injectiondrug users

Up to 2007 (no datesspecified in paper)

Si

Kimber et al.(2003)

Drug consumptionfacilities: an update since2000

Not specified Df

Tilson et al. (2007) Preventing HIV infectionamong injecting drug usersin high-risk countries: anassessment of the evidence

Up to Jan 2006 Sf

Wright andTompkins (2006)

A review of the evidencefor the effectiveness ofprimary preventioninterventions for HepatitisC among injecting drugusers

Up to end 2002 Dr

Wood (2006) Summary of findings fromthe evaluation of a pilotmedically supervised saferinjecting facility

2005–2006 Si

a Notifications of newly diagnosed infection.

al of Drug Policy 25 (2014) 34– 52 45

HCV transmissionWe did not identify any core reviews that examined the effects

of IEC in relation to HCV transmission (Table 3). One supplementaryreview (Hong & Li, 2009) identified a single serial cross-sectionalstudy that reported a reduction in HCV transmission associatedwith the introduction of a social marketing campaign in China (Wuet al., 2007). However, insufficient review-level evidence was iden-tified to support or discount the effectiveness of IEC in relation toHCV transmission.

Supervised injecting facilities (SIFs)

Injecting risk behaviourOne core review (Tilson et al., 2007) and six supplementary

reviews (Dolan et al., 2000; Hedrich, 2004; Kerr et al., 2007; Kimber,Dolan, Van Beek, Hedrich, & Zurhold, 2003; Wood, 2006; Wright &Tompkins, 2006) assessed effectiveness of SIFs (also known as drugconsumption rooms) in relation to IRB (Table 6).

Tilson et al. (2007) included two cross-sectional studies relat-ing to IRB (MSIC Evaluation Committee, 2003; Kerr, Tyndall, Li,Montaner, & Wood, 2005). One cross-sectional study (Kerr et al.,2005) in Vancouver demonstrated a statistically significant asso-ciation between attendance at the SIF and a reduction in thesharing of syringes (OR 0.30, 95% CI 0.11–0.82; p = 0.02), whilst across-sectional evaluation of a SIF in Australia (MSIC EvaluationCommittee, 2003) reported a non-significant difference in the useof sterile syringes and sharing of syringes or equipment amongSIF clients compared to non-SIF clients. Among the additional pri-mary studies identified in supplementary reviews, two prospective

cohort studies in Vancouver (Stoltz et al., 2007; Wood, Tyndall, &Stolz, 2005) and a series of cross-sectional studies relating to a SIFin Berne, Switzerland (Nejedly & burki, 1996; Reyes Fuentes, 2003;Ronco, Spuhler, & Kaiser, 1996) reported a positive association; and

ntervention covered ineview

Type of review Number of relevantprimary studiesincluded in the review,by outcome

rug consumptionacilities

Supplementary 4 IRB

upervised drugonsumption rooms

Supplementary 1 HCV/HIVa 1 HCV 12IRB

upervised safernjection facilities

Supplementary 10 IRB

rug consumptionacilities

Supplementary 2 IRB

upervised injectionacilities

Core 1 HCV/HIVa 2 IRB

rug consumptionooms

Supplementary 1 HCVa 5 IRB

upervised safernjecting facility

Supplementary 3 IRB

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wo cross-sectional studies (Benninghoff & Dubois-Arber, 2002;enninghoff, Solai, Huissoud, & Dubois-Arber, 2003) reported nossociation in reported sharing among SIF clients compared toWID (Table 6; Table 3; Supplementary Table 9). Additional stud-es that were included in core and supplementary reviews thateported impacts of SIFs on injecting practices outside the remitf our study are listed in Supplementary Table 9.

Tilson concluded that ‘the evidence regarding SIFs.whilstncouraging – is insufficient for drawing conclusions on the effec-iveness of this[sic] intervention in reducing drug-related HIV risksmong IDUs’, whilst Hedrich concluded that ‘consumption rooms.rovide a hygienic environment for drug use and, for regular atten-ees at least, decrease exposure to risks of infectious diseases.hey contribute to a reduction in levels of risk-taking among theirlients..’ Kerr et al. (2007) concluded that ‘a growing body of quanti-ative data point to the impact of SIF use on syringe sharing’. Basedn a statement of insufficient evidence from a core review, ten-ative statements of evidence from two supplementary reviews,nd evidence from a number of robust studies, we concludedhat there is tentative review-level evidence to support the effec-iveness of SIFs in reducing IRB and improving injecting hygieneTable 3).

IV transmissionTilson et al. (2007) included one serial cross-sectional study

also identified by Hedrich, 2004) which reported no evidence ofn increase or decrease in the number of HIV infections associatedith introduction of the SIF, although the authors note low preva-

ence of HIV among PWID over the time period of evaluation (MSICvaluation Committee, 2003). The authors of one of the supplemen-ary reviews (Kerr et al., 2007) concluded that SIFs can complementIV prevention strategies and that they can attract individualst heightened risk of HIV infection, but no primary studies werencluded in the review that directly assessed HIV transmission. Asuch, we concluded that there is insufficient review-level evidenceo support or discount the effectiveness of SIFs in relation to HIVransmission (Table 3).

CV transmissionTilson et al. (2007) and Hedrich (2004) reported findings of the

SIC evaluation (2003) outlined above, which reported no evi-ence of an increase or decrease in HCV incidence which coulde attributed to the SIF. Overall, therefore, in light of the lack ofobust studies relating to this outcome, we concluded that there isnsufficient review-level evidence to either support or discount theffectiveness of SIFs in relation to HCV transmission (Table 3).

iscussion

In this study, we have undertaken a RoR to update and expandn a previous study by our group (Palmateer et al., 2010) relat-ng to the effectiveness of harm reduction interventions for PWID.he RoR includes only the most robust reviews and takes intoccount the quality of the reviews, the conclusions of the reviewuthors, and the design and findings of primary studies included.he updated RoR identified sufficient or tentative review-level evi-ence to support the effectiveness of NSP, the provision of sterilerug preparation equipment, OST, IEC and SIFs in relation to IRBr HIV or HCV transmission among PWID. However, we found

lack of tentative or sufficient review-level evidence to supportffectiveness of any single intervention in relation to all threeutcomes.

Evidence was strongest for effectiveness of NSP and OST; foroth of these interventions we identified sufficient or tentative-eview-level evidence of effectiveness in relation to IRB and HIV.owever, despite identifying a number of reviews and primary

al of Drug Policy 25 (2014) 34– 52

studies that demonstrated effectiveness of interventions in rela-tion to IRB, we found little review-level evidence relating to theimpact on HCV transmission. Whilst we cannot discount the possi-bility that this finding may reflect the lack of recent reviews whichprevented inclusion of more recent studies relating to HCV trans-mission, the lack of review-level evidence is of concern given thehigh incidence and prevalence of HCV in PWID (Miller, Tyndall,Spittal, Li, & Laliberte, 2002; Nelson et al., 2011; Roy et al., 2006;Ruan et al., 2007; Turner et al., 2011) and the substantial morbid-ity and mortality associated with HCV infection (Wong, McQuillan,McHutchison, & Poynard, 2000).

However, it is possible that reductions in IRB observed in the pri-mary studies identified are not sufficient to reduce risk of incidentHCV infection. HCV has greater transmissibility via syringe shar-ing or needle-stick injury compared to HIV (Bell, 1997; Gerberding,1995) and very low levels of sharing (e.g. a few times per month)may be required to have a substantial impact on the extent of HCVtransmission between PWID, particularly among those that havebeen injecting for a number of years (Kretzschmar & Wiessing,1998; Vickerman, Hickman, & Judd, 2007). Moreover, evidence sug-gests that interventions need to target recent initiators of injectingdrug use as well as longer-term injectors to impact on HCV inci-dence (Vickerman et al., 2007).

Recent studies also report that combined provision of sev-eral harm reduction services at sufficient coverage have a greaterimpact on BBV transmission compared to single interventions(Degenhardt et al., 2010; Hagan et al., 2011; Turner et al., 2011;Van Den Berg et al., 2007) and it is possible that the provision ofNSP or OST alone is not sufficient to impact on HCV transmissionbetween PWID. A recent meta-analysis of UK studies demonstrateda synergistic impact of NSP and OST in relation to HCV incidencesuch that those receiving OST and at least one sterile needle fromNSP per injection had a 79% reduction in risk of HCV seroconversioncompared to those not receiving OST and with less than one ster-ile needle per injection (Turner et al., 2011), whilst a cohort studyreported greater benefit of participation in NSP and OST comparedto NSP or OST alone in relation to both HCV and HIV transmission(Van Den Berg et al., 2007). Modelling studies also suggest that NSPand OST have a greater impact on HIV incidence at higher coverage(Degenhardt et al., 2010).

Despite these findings, global provision of key interventionsremains low with just 6–12% of PWID estimated to be in receiptof OST and 1–4 needles and syringes estimated to be distributedper PWID per month (Mathers, 2010; Sharma, Burrows, andBluthenthal, 2007). Critically, provision is minimal in many of thecountries where the incidence and prevalence of both HIV and HCVis highest (Mathers, 2010; Mathers et al., 2008; Nelson et al., 2011;Sharma et al., 2007). Taken together, the above studies suggestthat scale up of combinations of harm reduction interventions pro-vided with sufficient coverage is needed to impact on HCV and HIVincidence.

Where services are provided, the mode of their delivery mayneed to be tailored to account for different characteristics andpatterns of drug use among attendees (Craine et al., 2010) to facil-itate maximum attendance and thus high coverage. For instance,in relation to NSP, low prices, access to NSP, convenience of loca-tion and time, supportive attitudes, and the option to receiveadditional services all facilitate attendance, whilst inconvenientopening hours, a lack of privacy and a fear of being caught by policecan act as barriers to attendance (Green et al., 2010; Trubnikov,Khodakevich, Barkov, & Blagovo, 2003) (Cooper et al., 2011; Sarang,Rhodes, & Platt, 2008; Voytek, Sherman, & Junge (2003); Williams

and Metzger, 2010). A greater awareness of preferred models ofdelivery of services among PWID and the impact of setting mayenhance their potential effectiveness in preventing HIV and HCVinfection.
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Whilst much of the evidence focused on effectiveness of NSP andST, the lack of primary and review-level evidence relating to theffectiveness of additional harm reduction interventions is of con-ern and must not be overlooked. Although we identified additionalvidence and/or updated evidence statements following our previ-us study (Palmateer et al., 2010), either no reviews or insufficienteview-level evidence were identified in relation to SIFs, IEC, therovision of drug preparation equipment and alternative access toSP in relation to HCV and HIV incidence. We acknowledge, how-ver, that SIFs are not a common intervention which may accountor the lack of evidence on the effectiveness of this intervention.ur finding is supported by recent systematic reviews that identi-ed a small number of robust studies and a lack of effectiveness ofehavioural interventions, non-OST drug treatment, and syringeisinfection in relation to HCV and HIV incidence (Hagan et al.,011; Sacks-Davis et al., 2011; Tilson et al., 2007). Further studiesre needed to examine the impact of the full range of available inter-entions and the effectiveness of combinations of interventions inelation to HIV/HCV incidence in PWID.

We have used a rigorous process to identify and appraise thevailable evidence, and have derived evidence statements in thisaper based on the quality of the reviews, the conclusions of reviewuthors, and designs and findings of primary studies included inhe reviews. However, it must be noted that the ‘review of reviews’

ethod has limitations. It is possible that relevant primary stud-es might not have been included in the reviews identified; wencluded core reviews covering papers on the key interventionsublished up to 2006, and supplementary reviews covering papersublished up to 2010 (up to 2007 for SIFs). The studies identified

n different reviews, the extent to which authors considered biasnd limitations of individual studies, and the conclusions drawny authors were variable between reviews. The inclusion only ofeviews published in the English language may also have excludedmportant studies.

Identification of insufficient review-level evidence relatingo particular interventions does not necessarily highlight a lackf effectiveness, but rather a gap in the evidence base, a lack ofdequate power to detect an effect in primary studies, inappro-riate design of studies, or findings that may not yet have beenublished. Furthermore, variation in contextual factors betweenarm reduction programmes, variability in prevalence and inci-ence of HIV or HCV and the inclusion of PWID at highest risk, may

imit the conclusions that can be drawn (Bastos and Strathdee,000; Bruneau, Franco et al., 1997; Bruneau et al., 1997; Strathdee,atrick, Archibald et al., 1997).

Although we have considered the ‘weight’ of evidence primarilyn relation to study design, primary studies in this field may alsoe at risk of bias, due to weaker study design and the inclusion of aelf-selecting group of people who inject drugs that access serviceshich may over or underestimate the effects reported (Bruneau,

ranco et al., 1997; Bruneau et al., 1997; Sorensen and Copeland,000; Strathdee, Patrick, Archibald et al., 1997; Tilson et al., 2007).otably, the authors of reviews identified in our study empha-

ised the difficulties of examining the impact of single interventionsn isolation, given that other interventions may be available con-urrently or may even be part of the intervention under study.evertheless, evidence relating to the impact of combinations of

nterventions is increasing.Overall, our findings demonstrate that whilst individual harm

eduction interventions such as OST, NSP or IEC can be effectiven reducing HIV or HCV transmission and/or IRB, the evidencease regarding the impact of the range of harm reduction inter-

entions on HIV and HCV transmission remains limited. Emergingvidence indicates that interventions need to be provided atigh coverage and in combination to minimise the risk of HCVnd HIV infection in PWID. As such, there remains a clear need

al of Drug Policy 25 (2014) 34– 52 47

to strengthen the evidence base pertaining to the effectiveness,and the impact of scaling up, of a range and combination ofharm reduction interventions in different settings to preventHIV and HCV infection across populations of people who injectdrugs.

Funding

This work was supported by the European Centre for DiseasePrevention and Control (ECDC) and the European Monitoring Cen-tre for Drugs and Drug Addiction (EMCDDA).

GJM was supported by the South West Public Health TrainingScheme, UK.

The funders did not influence the design of the study, analysisor interpretation of data.

Appendix A. Supplementary data

Supplementary material related to this article can be found,in the online version, at http://dx.doi.org/10.1016/j.drugpo.2013.07.001.

Conflict of interest

Conflict of Interest to be provided at a later date.

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