Hepatitis C virus (HCV) infection is a source of significant and costly morbidity and mortality in the United States. Chronic HCV infection significantly increases the risk of liver disease, especially cirrhosis and liver cancer. It is estimated that one third of all persons currently awaiting a liver transplant have HCV-associated liver disease.
Although HCV can be transmitted in several ways, the primary mode of HCV exposure is percutaneous with injection drug use remaining the largest risk factor for HCV infection. Injection drug users account for approximately 60%-70% of the incidence of new HCV infections in the United States. The prevalence of HCV infection in injection drug users ranges between 40% and 90% and has been observed to be as high as 98%. Harm reduction interventions aim to reduce individual and societal harms stemming from drug use by targeting risky behaviors and risky settings. A needle exchange program (NEP) is one popular harm reduction intervention that seeks to reduce risky settings by providing clean needles in exchange for used needles to minimize the reuse of needles contaminated with HCV during drug injection. Unfortunately, studies examining the relationship between needle exchange programs and the prevention of HCV in people who inject drugs remain equivocal. Given the former, the primary objective of this study is to conduct a systematic review with meta-analysis to determine the effects of needle exchange programs on preventing HCV in people who inject drugs.
The a priori inclusion criteria for this systematic review with meta-analysis will be as follows:
(1) observational studies,
(2) injection drug users,
(3) NEP use,
(4) HCV status ascertained by serological testing (saliva or serum),
(5) studies published after January 1, 1989, and
(6) data available or calculable for measures of association between participation in a NEP and HCV infection.
Studies will be excluded based on inappropriate study design, population, intervention, or lack of available information to calculate a measure of association between program participation and HCV seroconversion. Studies published in any language will be considered.
The following four databases will be searched for studies published after January 1, 1989:
(3) Web of Science and
In addition, cross-referencing from retrieved studies and reviews will also be conducted. The following search terms and combinations will be used: (hepatitis C OR HCV) AND (intravenous drug abuse OR intravenous drug use OR drug misuse OR drug addict OR injecting drug use OR drug abuse OR people who inject drugs OR IDU OR PWID) AND (prevention OR risk factor OR epidemiology OR prevalence OR incidence OR seroprevalence OR seroincidence OR seroconversion OR genotype OR coinfect*) AND (needle exchange OR needle exchange program OR syringe exchange program OR syringe access program) AND ("1989/01/01"[Date - Publication] : "3000"[Date - Publication]).
Types of study to be included
Studies will be eligible if they are observational studies that present data which allow calculation of a measure of association between needle exchange program attendance and HCV seroconversion.
Condition or domain being studied
The primary outcome for this study is Hepatitis C virus (HCV) infection.
Studies will be limited to participants who are injection drug users regardless of age, gender, race, or other demographic factors. Any studies not meeting these participant criteria will be excluded.
The exposure for this study is a needle exchange program.
The control condition will be non-attenders of a needle exchange program.
Needle exchange programs that provide clean needles in exchange for used needles will be included. Pharmacies or other sites that only provide clean syringes with no needle exchange will be excluded.
Supervised injection facilities will also be excluded because needle exchange may not always occur at such sites.
Hepatitis C virus seroconversion.
Injection behavior (number of times a clean needle is used, sharing or borrowing of needles).
Data extraction, (selection and coding)
Two researchers will independently review studies for selection and abstract data from eligible studies. Discrepancies will be resolved by consensus and if necessary, discussion with a third researcher. A codebook will be developed using Microsoft Excel. The major categories of variables coded will include
(1) study characteristics (author, journal, year, funding status, design, inclusion criteria, recruitment method, recruitment locations, method of determining injection drug use status, specimen type, and HCV test method, etc.),
(2) participant characteristics (age, gender, ethnicity, duration of drug use, type of drug used, frequency of use, etc.), and
(3) outcome characteristics (prevalence, incidence, number of person years, sample size, variables adjusted).
Risk of bias (quality) assessment
Risk of bias will be assessed using the Newcastle-Ottawa Scale.
Strategy for data synthesis
An aggregate data meta-analysis is planned. The overall relative risk (or odds ratio) of HCV seroconversion will be calculated for each result from each study. Results will then be pooled using the random-effects model of DerSimonian and Laird. Heterogeneity will be assessed using Cochran's Q statistic while inconsistency will be assessed using I-squared. Assuming at least 10 effect sizes, small-study effects (publication bias, etc.) will be assessed using funnel plots and Egger’s regression intercept test (one-tailed). Influence analysis will be conducted with each study deleted from the model once in order to examine the effects of each study result on the overall pooled effect. Cumulative meta-analysis, ranked by year of publication, will be conducted in order to examine the accrued results over time. To assess the robustness of results, sensitivity analysis will be conducted by examining whether or not results are sensitive to different observational study designs. Mixed-effects meta-regression will be used to examine for potential covariates.
Analysis of subgroups or subsets
This review will be submitted for presentation consideration at a professional conference as well as being submitted for publication consideration in a peer-reviewed journal.
Contact details for further information
WVU Department of Emergency Medicine
1 Medical Center Drive, HSS Rm. 2223
Morgantown, WV 26506
Organisational affiliation of the review
West Virginia University, Departments of Emergency Medicine, Social and Behavioral Sciences, Biostatistics, and Medicine, Section of Infectious Diseases
Professor Stephen Davis, Department of Emergency Medicine, West Virginia University Dr Alfgeir Kristjansson, Department of Social and Behavioral Sciences, West Virginia University Dr George Kelley, Department of Biostatistics, West Virginia University Dr Melanie Fisher, Department of Medicine, Section of Infectious Diseases, West Virginia Univeristy Mr Shay Daily, Department of Social and Behavioral Sciences, West Virginia University
Anticipated or actual start date
11 July 2016
Anticipated completion date
30 July 2017
G. Kelley is partially supported by the National Institute of General Medical Sciences, Award #U54GM104942. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Formal screening of search results against eligibility criteria
Risk of bias (quality) assessment
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.