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Review
. 2017 Sep 18;9(9):CD012021.
doi: 10.1002/14651858.CD012021.pub2.

Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs

Lucy Platt  1 , Silvia Minozzi, Jennifer Reed, Peter Vickerman, Holly Hagan, Clare French, Ashly Jordan, Louisa Degenhardt, Vivian Hope, Sharon Hutchinson, Lisa Maher, Norah Palmateer, Avril Taylor, Julie Bruneau, Matthew Hickman
Affiliations
Review

Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs

Lucy Platt et al. Cochrane Database Syst Rev. .

Abstract

Background: Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak.

Objectives: To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs.

Search methods: We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers.

Selection criteria: We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at an NSP or all injections covered by a new needle/syringe) or low NSP coverage (irregular attendance at an NSP or less than 100% of injections covered by a new needle/syringe) compared with no intervention or reduced exposure.

Data collection and analysis: We followed the standard Cochrane methodological procedures incorporating new methods for classifying risk of bias for observational studies. We described study methods against the following 'Risk of bias' domains: confounding, selection bias, measurement of interventions, departures from intervention, missing data, measurement of outcomes, selection of reported results; and we assigned a judgment (low, moderate, serious, critical, unclear) for each criterion.

Main results: We identified 28 studies (21 published, 7 unpublished): 13 from North America, 5 from the UK, 4 from continental Europe, 5 from Australia and 1 from China, comprising 1817 incident HCV infections and 8806.95 person-years of follow-up. HCV incidence ranged from 0.09 cases to 42 cases per 100 person-years across the studies. We judged only two studies to be at moderate overall risk of bias, while 17 were at serious risk and 7 were at critical risk; for two unpublished datasets there was insufficient information to assess bias. As none of the intervention effects were generated from RCT evidence, we typically categorised quality as low. We found evidence that current OST reduces the risk of HCV acquisition by 50% (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.40 to 0.63, I2 = 0%, 12 studies across all regions, N = 6361), but the quality of the evidence was low. The intervention effect remained significant in sensitivity analyses that excluded unpublished datasets and papers judged to be at critical risk of bias. We found evidence of differential impact by proportion of female participants in the sample, but not geographical region of study, the main drug used, or history of homelessness or imprisonment among study samples.Overall, we found very low-quality evidence that high NSP coverage did not reduce risk of HCV acquisition (RR 0.79, 95% CI 0.39 to 1.61) with high heterogeneity (I2 = 77%) based on five studies from North America and Europe involving 3530 participants. After stratification by region, high NSP coverage in Europe was associated with a 76% reduction in HCV acquisition risk (RR 0.24, 95% CI 0.09 to 0.62) with less heterogeneity (I2 =0%). We found low-quality evidence of the impact of combined high coverage of NSP and OST, from three studies involving 3241 participants, resulting in a 74% reduction in the risk of HCV acquisition (RR 0.26 95% CI 0.07 to 0.89).

Authors' conclusions: OST is associated with a reduction in the risk of HCV acquisition, which is strengthened in studies that assess the combination of OST and NSP. There was greater heterogeneity between studies and weaker evidence for the impact of NSP on HCV acquisition. High NSP coverage was associated with a reduction in the risk of HCV acquisition in studies in Europe.

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Conflict of interest statement

Lucy Platt: none known.

Jennifer Reed: none known.

Silvia Minozzi: none known.

Peter Vickerman: received research grant funding off Gilead for doing work unrelated to this project.

Holly Hagan: none known.

Clare French: none known.

Ashly Jordan: none known.

Louisa Degenhardt: I have received untied educational grants from Reckitt Benckiser for the postmarketing surveillance of buprenorphine‐naloxone tablets and soluble film (2006 to 2013), the development of an opioid‐related behaviour scale (2010), and from Mundipharma for the conduct of postmarketing surveillance studies following the introduction of a new formulation of oxycodone in Australia. All such studies' design, conduct and interpretation of findings are the work of the investigators; the funders had no role in these. They had no knowledge of this work.

Vivian Hope: none known.

Sharon Hutchinson: outside the submitted work, received honoraria from pharma (Abbvie and Gilead) for speaking at conferences/meetings on the epidemiology and treatment of HCV infection.

Lisa Maher: none known.

Norah Palmateer: none known.

Avril Taylor: the Scottish Government funded the Needle Exchange Surveillance Initiative. Some of the data from this is used in the paper under consideration.

Julie Bruneau: outside the submitted work, received honoraria from pharma (Merck and Gilead) as advisor on the treatment of HCV infection among people who inject drugs.

Matthew Hickman: none known.

Figures

1
1
Study flow diagram.
2
2
Forest plot of comparison: 1 Current OST versus no OST, outcome: 1.1 HCV incidence adjusted analyses by region.
3
3
Funnel plot of comparison: 1 Current OST versus no OST, outcome: 1.1 HCV incidence adjusted analyses by region.
4
4
Forest plot of comparison: 2 High NSP coverage versus no/low NSP coverage, outcome: 2.1 HCV incidence adjusted analyses by region.
5
5
Forest plot of comparison: 4 Combined OST and high/low NSP versus no OST and low/no NSP, outcome: 4.1 HCV incidence adjusted analyses.
1.1
1.1. Analysis
Comparison 1 Current OST versus no OST, Outcome 1 HCV incidence adjusted analyses by region.
1.2
1.2. Analysis
Comparison 1 Current OST versus no OST, Outcome 2 HCV incidence adjusted analysis by study design.
1.3
1.3. Analysis
Comparison 1 Current OST versus no OST, Outcome 3 HCV incidence unadjusted analyses by different modes of OST provision.
2.1
2.1. Analysis
Comparison 2 Sensitivity analysis: OST versus no OST, adjusted analyses excluding unpublished datasets, Outcome 1 HCV incidence.
3.1
3.1. Analysis
Comparison 3 Sensitivity analysis: OST versus no OST, adjusted analyses excluding studies at critical risk of bias, Outcome 1 HCV incidence.
4.1
4.1. Analysis
Comparison 4 Sensitivity analysis: OST versus no OST, adjusted analyses excluding cross‐sectional studies, Outcome 1 HCV incidence.
5.1
5.1. Analysis
Comparison 5 OST versus no OST, unadjusted analysis, Outcome 1 HCV incidence.
6.1
6.1. Analysis
Comparison 6 High NSP coverage versus no/low NSP coverage, Outcome 1 HCV incidence adjusted analyses by region.
6.2
6.2. Analysis
Comparison 6 High NSP coverage versus no/low NSP coverage, Outcome 2 HCV incidence adjusted analyses by study design.
7.1
7.1. Analysis
Comparison 7 Sensitivity analysis: high NSP versus low/no NSP, excluding unpublished data, Outcome 1 HCV incidence.
8.1
8.1. Analysis
Comparison 8 Sensitivity analysis: high NSP versus low/no NSP, excluding cross‐sectional surveys, Outcome 1 HCV incidence.
9.1
9.1. Analysis
Comparison 9 High NSP coverage versus low/no coverage, unadjusted estimates, Outcome 1 HCV incidence.
10.1
10.1. Analysis
Comparison 10 Low NSP coverage versus no coverage, Outcome 1 HCV incidence, adjusted analyses.
11.1
11.1. Analysis
Comparison 11 Low NSP coverage versus no NSP, unadjusted analysis, Outcome 1 HCV incidence.
12.1
12.1. Analysis
Comparison 12 Combined OST and high/low NSP versus no OST and low/no NSP, Outcome 1 HCV incidence adjusted analyses.
12.2
12.2. Analysis
Comparison 12 Combined OST and high/low NSP versus no OST and low/no NSP, Outcome 2 HCV incidence unadjusted analyses.
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Mikolajczyk 2013 {published data only}
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Nasir 2011 {published data only}
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Parrino 2003 {published data only}
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Peles 2011 {published data only}
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Sanders‐Buell 2013 {published data only}
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Seal 2004 {published data only}
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Shi 2007 {published data only}
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Solomon 2010 {published data only}
    1. Solomon SS, Celentano DD, Srikrishnan AK, Vasudevan CK, Murugavel KG, Iqbal SH, et al. Low incidences of human immunodeficiency virus and hepatitis C virus infection and declining risk behaviors in a cohort of injection drug users in Chennai, India. American Journal of Epidemiology 2010;172(11):1259‐67. - PMC - PubMed
Spencer 1997 {published data only}
    1. Spencer JD, Latt N, Beeby PJ, Collins E, Saunders JB, McCaughan GW, et al. Transmission of hepatitis C virus to infants of human immunodeficiency virus‐negative intravenous drug‐using mothers: rate of infection and assessment of risk factors for transmission. Journal of Viral Hepatitis 1997;4(6):395‐409. - PubMed
Steffen 2001 {published data only}
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Stephens 2013 {published data only}
    1. Stephens BP, Tait J, Evans M, Dillon JF. The natural history of the acquisition of HCV in chaotic PWID. Hepatology 2013;58:1103A.
Strathdee 1997 {published data only}
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Sylvestre 2006 {published data only}
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Tait 2013a {published data only}
    1. Tait JM, Stephens BP, McIntyre P, Evans M, Dillon JF. Dry blood spot testing for hepatitis C in people who injected drugs: reaching the populations other tests cannot reach. Journal of Hepatology 2013;58:S204. - PMC - PubMed
Tait 2013b {published data only}
    1. Tait J, Stephens BP, Evans M, Cleary S, Dillon JF. People who inject drugs (PWID): difficult to get into services, easy to cure. Hepatology 2013;58:1102A‐3A.
Todd 2015 {published data only}
    1. Todd CS, Nasir A, Stanekzai MR, Fiekert K, Sipsma HL, Vlahov D, et al. Hepatitis C and HIV incidence and harm reduction program use in a conflict setting: an observational cohort of injecting drug users in Kabul, Afghanistan. Harm Reduction Journal 2015;12(1):Article Number: 22. [DOI: 10.1186/s12954-015-0056-z] - DOI - PMC - PubMed
Tracy 2014 {published data only}
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Tsirogianni 2013 {published data only}
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Tsui 2009 {published data only}
    1. Tsui JI, Vittinghoff E, Hahn JA, Evans JL, Davidson PJ, Page K. Risk behaviors after hepatitis C virus seroconversion in young injection drug users in San Francisco. Drug and Alcohol Dependence 2009;105(1‐2):160‐3. - PMC - PubMed
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    1. Valdez A, Neaigus A, Kaplan C, Cepeda A. High rates of transitions to injecting drug use among Mexican American non‐injecting heroin users in San Antonio, Texas (never and former injectors). Drug and Alcohol Dependence 2011;114(2‐3):233‐6. - PMC - PubMed
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References to studies awaiting assessment

Bruneau 2016 {published data only}
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Chun 2006 {published data only}
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Duan 2013 {published data only}
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