Opiate substitution therapy halves HIV risk for people who inject drugs

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Opiate substitution therapy reduces the risk of HIV infection by half for individuals who inject drugs, according to the results of a systematic review and meta-analysis published in the British Medical Journal.

“There is evidence from published and unpublished observational studies that opiate substitution treatment is associated with an average 54% reduction in the risk of new HIV infections among people who inject drugs,” write the investigators. “To our knowledge this is the first study that synthesises the available evidence and generates a quantitative estimate of the impact of opiate substitution treatment on incidence of HIV.”

Injecting drug users are among the groups most affected by HIV. Up to 40% of injecting drugs users in some settings are infected with the virus, and emerging epidemics in parts of Russia, eastern Europe and Asia are largely driven by injecting drug use.


person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

systematic review

A review of the findings of all studies which relate to a particular research question and which conform to pre-determined selection criteria. 


When the statistical data from all studies which relate to a particular research question and conform to a pre-determined selection criteria are pooled and analysed together.

case-control study

An observational study in which a group of people with an infection or condition (called ‘cases’) are compared with a group of people without the infection or condition (called ‘controls’). The past events and behaviour of the two groups are compared. Case-control studies can help us understand the risk factors for having an infection or a condition. However, it is difficult both to accurately collect information about past events and to eliminate bias from case-control studies.

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

Methadone or buprenorphine are prescribed to people who are dependant on opiates, and both drugs are on the World Health Organization list of essential medicines. In addition to reducing craving for illicit substances, therapy with these drugs has been shown to have other benefits. These include reductions in drug-related mortality, reduced offending and improved adherence to antiretroviral therapy.

There is also some evidence that injecting drug users who are prescribed opiate substitution therapy have a reduced risk of infection with HIV.

An international team of investigators wanted to establish a clearer understanding of the impact of opiate substitution treatment in relation to HIV incidence among injecting drug users.

They therefore conducted a systematic review and meta-analysis of the results of randomised studies, prospective cohort studies, or case-control studies that directly examined the effect of opiate substitution therapy on HIV incidence in injecting drug users.

Studies published up to March 2011 were included in the investigators’ analyses.

A total of 15 studies were identified. All looked at the impact of methadone maintenance therapy. The size of the studies ranged from 80 to 2546 individuals; the duration of follow-up was between one and 20 years; and the research was published between 1992 and 2009.

The authors were able to pool the results of nine studies to assess the impact of opiate substitution treatment in relation to HIV transmission. The results of these studies provided 819 incident HIV infections over 23,607 person-years of follow-up.

Overall, opiate substitution treatment reduced the risk of infection with HIV by 54% (RR = 0.46; 95% CI, 0.32-0.67, p < 0.001).

The authors then restricted their analysis to the six studies that adjusted for confounders. A total of 450 incident infections were reported in these studies over 10,064 person-years of follow-up. Methadone substitution therapy reduced the risk of infection with HIV by 40% (RR = 0.60; 95% CI, 0.42-0.85, p = 0.004).

A significant benefit of opiate substitution therapy on HIV transmission risk continued to be evident when the authors restricted their analysis to the five studies with the lowest risk of bias (RR = 0.61; 95% CI, 0.41-0.91, p = 0.016).

There was no evidence that the benefits of opiate replacement therapy differed by region or were affected by the provision of incentives to people. However, there was a weak association between longer duration of substitution therapy and greater benefit in terms of reduced HIV incidence.

Four studies looked at the impact of methadone detoxification treatment. There were 687 incident HIV infections over 20,616 person-years of follow-up in these studies. The pooled results showed detoxification therapy was associated with an increased risk of infection with HIV when compared to either no treatment or methadone replacement therapy (RR = 1.54; 95% CI, 1.05-2.26, p = 0.026).

“Our findings further support and highlight the importance of opiate substitution treatment in the prevention of HIV among people who inject [opiate] drugs,” comment the investigators. “These data further support studies showing a range of benefits of opiate substitution treatment, and support 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.”


MacArthur GJ et al. Opiate substitution treatment and HIV transmission in people who inject drugs: a systematic review and meta-analysis. BMJ 345: e5945 (doi: 10.1136/bmj.e5945), 2012.