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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis

GJ MacArthur, S Minozzi, N Martin, P Vickerman, S Deren, J Bruneau, L Degenhardt, and M Hickman.

Review published: 2012.

CRD summary

This generally well-conducted review concluded that opiate substitution as maintenance therapy reduced the risk of HIV infection among people who inject drugs. The authors acknowledged the limitations of the evidence, and that high levels of motivation to change behaviour participants of such studies may mean the results were not generalisable. These conclusions are likely to be reliable.

Authors' objectives

To quantify the effect of opiate substitution treatment in relation to HIV transmission among people who inject drugs. Secondary objectives were to examine the effect of aspects of treatment regimen such as dose and duration, geographical region, setting, and characteristics of participants.


MEDLINE, EMBASE, PsycINFO, and The Cochrane Library were searched without language restrictions from inception to October 2011 without language restrictions. Reference lists of well-conducted reviews were also searched. The search strategy was apparently available in a separate online appendix, but this could not be located.

Study selection

Randomised controlled trials (RCTs), prospective cohort studies or case-control studies of people who inject drugs that directly examined the impact of opiate substitution treatment on HIV incidence were eligible for inclusion. Studies that prospectively examined HIV incidence in people who inject drugs but did not report data on the impact of opiate substitution treatment were also eligible. Studies were included if they assessed: the impact of continuous or interrupted opiate substitution treatment; current, recent, or previous opiate substitution treatment; or opiate substitution treatment at baseline. Cross-sectional studies, retrospective analysis of routine medical records, studies conducted in prisons, and studies that reported fewer than two seroconversions during follow-up were excluded.

Most of the included studies were conducted in the USA or Canada. Across studies included in the meta-analysis, the median age ranged from 26 to 39 years, the proportion of men ranged from 61% to 93%, and the proportion from an ethnic minority group ranged from 15% to 92%.

Two independent reviewers selected studies for the review; disagreements were resolved by discussion.

Assessment of study quality

Study quality was assessed for sequence generation, allocation concealment, performance bias, detection bias, attrition bias, comparability of cohorts, selection of non-exposed participants, contamination and ascertainment bias.

The authors did not report how many reviewers performed the quality assessment.

Data extraction

Two reviewers extracted incidence rates, or unadjusted and adjusted measures of effect (along with the adjustment for confounders). Odd ratios (OR) and 95% confidence intervals (CI) were calculated. The authors of studies that did not report data on the impact of opiate substitution treatment were contacted to obtain unpublished results. Poisson regression was used to obtain incidence rate ratios and 95% confidence intervals from raw data in unpublished datasets, and where information on seroconversion and person years of follow-up was provided in published studies. Where more than one paper was available from the same cohort study, those that had the largest number of seroconversions and/or that reported adjusted and unadjusted analyses were selected.

Methods of synthesis

Pooled odds ratios and 95% confidence intervals were calculated using a random-effects meta-analysis. Heterogeneity was assessed using Χ² and Ι². Studies that examined methadone maintenance treatment compared with methadone detoxification treatment were excluded from the primary meta-analysis; these were included in subgroup analyses. Adjusted and unadjusted effect estimates were pooled in separate analyses.

Univariable random-effects meta-regression was used to investigate geographical region, the provision of monetary incentives, site of recruitment, duration of exposure to opiate substitution treatment, gender and ethnicity. Sensitivity analyses were conducted to assess the impact of exposure to methadone maintenance treatment at baseline, risk of bias, studies measuring incidence rate ratio, and adjustment for confounders.

Publication bias was assessed using a funnel plot and the Egger test.

Results of the review

Fifteen studies were included in the review (10,654 participants, range 80 to 2546; 1016 incident HIV infections; over 26,738 person years of follow-up). All of the included studies were judged to be at high risk of selection bias and low risk of performance bias; most were at low risk of ascertainment bias. Nine studies had a high risk of attrition bias. Few adjusted for confounders. Nine studies were included in the meta-analysis (819 incident HIV infections; 23,608 person years of follow-up).

Opiate substitution was associated with a 54% reduction in the risk of HIV infection (rate ratio 0.46, 95% CI 0.32 to 0.67; Ι²=60%). Studies that adjusted for confounders showed methadone maintenance to be associated with a 40% reduction in the risk of incident HIV (rate ratio 0.60, 95% CI 0.42 to 0.85; Ι²=23%; six studies; 450 incident HIV infections; 10,064 person years of follow-up).

Inclusion of data evaluating the impact of methadone maintenance at baseline, studies at a low risk of bias, and studies reporting estimates only as incidence rate ratio, gave similar results.

Meta-regression showed no evidence that the effectiveness of opiate substitution varied according to geographical region, site of recruitment, provision of incentives to participants, or ethnicity. There was weak evidence that longer duration of exposure to opiate substitution treatment could be associated with greater benefit.

Methadone detoxification treatment (four studies; 687 incident HIV infections; 20,616 person years of follow-up) was not associated with a decreased risk of HIV infection compared with either no treatment or methadone maintenance treatment (relative risk 1.54, 95% CI 1.05 to 2.26).

There was weak evidence of publication bias.

Authors' conclusions

Opiate substitution treatment provided as maintenance therapy was associated with a reduction in the risk of HIV infection among people who inject drugs. However, these findings could reflect comparatively high levels of motivation to change behaviour and reduce injecting risk behaviour among people who inject drugs who were receiving opiate substitution treatment.

CRD commentary

The review had clearly stated objectives and reproducible inclusion criteria. Several relevant sources were searched with no language restrictions. Unpublished data from relevant published studies identified were obtained. Study selection and data extraction were conducted in duplicate; it was unclear whether similar methods to reduce error and bias were employed during the quality assessment.

Study quality was assessed using appropriate criteria and the results were published in full. The impact of study quality was explored in the analysis. Appropriate methods of synthesis were employed. Relevant potential sources of heterogeneity were investigated. The authors acknowledged a range of limitations of the available evidence base, and that the results and conclusions may not be generalisable.

This was a generally well-conducted review and the conclusions, with the stated caveats, are likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that these data supported calls for the global increase of harm reduction interventions to reduce the transmission of HIV between people who inject drugs, and between people who inject drugs and the wider community.

Research: The authors stated that further studies were needed to assess the impact of 'comprehensive' or combinations of interventions, including opiate substitution treatment, in a range of settings including prison. Further evidence of the effectiveness of harm reduction approaches was also required in low and middle income countries.


British Heart Foundation, Cancer Research UK, Economic and Social Research Council; The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement; Medical Research Council; the Welsh Assembly Government; the Wellcome Trust. Individual authors received funding from a range of institutions.

Bibliographic details

MacArthur GJ, Minozzi S, Martin N, Vickerman P, Deren S, Bruneau J, Degenhardt L, Hickman M. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ 2012; 345:e5945. [PMC free article: PMC3489107] [PubMed: 23038795]

Indexing Status

Subject indexing assigned by NLM


Confounding Factors (Epidemiology); Disease Transmission, Infectious /prevention & control /statistics & numerical data; HIV Infections /epidemiology /prevention & control /transmission; Humans; Methadone /administration & dosage; Narcotics /administration & dosage; Opiate Substitution Treatment /methods; Primary Prevention /methods; Prospective Studies; Research Design; Risk Factors; Substance Abuse, Intravenous /complications /drug therapy; Time Factors



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 23038795

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