Search

BACKGROUND: Opioid dependence (OD) is an increasing clinical and public health problem worldwide. International guidelines recommend opioid substitution treatment (OST), such as methadone and buprenorphine, as first‐line medication treatment for OD. A negative aspect of OST is that the medication used can be diverted both through sale on the black market, and the unsanctioned use of medications. Daily supervised administration of medications used in OST has the advantage of reducing the risk of diversion, and may promote therapeutic engagement, potentially enhancing the psychosocial aspect of OST, but costs more and is more restrictive on the client than dispensing for off‐site consumption. OBJECTIVES: The objective of this systematic review is to compare the effectiveness of OST with supervised dosing relative to dispensing of medication for off‐site consumption. SEARCH METHODS: We searched in Cochrane Drugs and Alcohol Group Specialised Register and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science from inception up to April 2016. Ongoing and unpublished studies were searched via ClinicalTrials.gov (www.clinicaltrials.gov) and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/). All searches included non‐English language literature. We handsearched references on topic‐related systematic reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials (CCTs), and prospective controlled cohort studies, involving people who are receiving OST (methadone, buprenorphine) and comparing supervised dosing with dispensing of medication to be consumed away from the dispensing point, usually without supervision. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: Six studies (four RCTs and two prospective observational cohort studies), involving 7999 participants comparing supervised OST treatment with unsupervised treatment, met the inclusion criteria. The risk of bias was generally moderate across trials, but the results reported on outcomes that we planned to consider were limited. Overall, we judged the quality of the evidence from very low to low for all the outcomes. We found no difference in retention at any duration with supervised compared to unsupervised dosing (RR 0.99, 95% CI 0.88 to 1.12, 716 participants, four trials, low‐quality evidence) or in retention in the shortest follow‐up period, three months (RR 0.94; 95% CI 0.84 to 1.05; 472 participants, three trials, low‐quality evidence). Additional data at 12 months from one observational study found no difference in retention between groups (RR 0.94, 95% CI 0.77 to 1.14; n = 300).There was no difference in abstinence at the end of treatment (self‐reported drug use) (67% versus 60%, P = 0.33, 293 participants, one trial, very low‐quality evidence); and in diversion of medication (5% versus 2%, 293 participants, one trial, very low‐quality evidence). Regarding our secondary outcomes, we did not found a difference in the incidence of adverse effects in the supervised compared to unsupervised control group (RR 0.63; 96% CI 0.10 to 3.86; 363 participants, two trials, very low‐quality evidence). Data on severity of dependence were very limited (244 participants, one trial) and showed no difference between the two approaches. Data on deaths were reported in two studies. One trial reported two deaths in the supervised group (low‐quality evidence), while in the cohort study all‐cause mortality was found lower in regular supervision group (crude mortality rate 0.60 versus 0.81 per 100 person‐years), although after adjustment insufficient evidence existed to suggest that regular supervision was protective (mortality rate ratio = 1.23, 95% CI = 0.67 to 2.27). No studies reported pain symptoms, drug craving, aberrant opioid‐related behaviours, days of unsanctioned opioid use and overdose. AUTHORS' CONCLUSIONS: Take‐home medication strategies are attractive to treatment services due to lower costs, and place less restrictions on clients, but it is unknown whether they may be associated with increased risk of diversion and unsanctioned use of medication. There is uncertainty about the effects of supervised dosing compared with unsupervised medication due to the low and very low quality of the evidence for the primary outcomes of interest for this review. Data on defined secondary outcomes were similarly limited. More research comparing supervised and take‐home medication strategies is needed to support decisions on the relative effectiveness of these strategies. The trials should be designed and conducted with high quality and over a longer follow‐up period to support comparison of strategies at different stages of treatment. In particular, there is a need for studies assessing in more detail the risk of diversion and safety outcomes of using supervised OST to manage opioid dependence.

Background Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. Objectives To assess the effects of buprenorphine versus tapered doses of methadone, alpha2-adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. Selection criteria Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2-adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction. For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to ameliorate opioid withdrawal, without clinically significant adverse effects. The meta-analyses that were possible support a conclusion of no difference between buprenorphine and methadone in terms of average treatment duration (mean difference (MD) 1.30 days, 95% confidence interval (CI) −8.11 to 10.72; N = 82; studies = 2; low quality) or treatment completion rates (risk ratio (RR) 1.04, 95% CI 0.91 to 1.20; N = 457; studies = 5; moderate quality). Relative to clonidine or lofexidine, buprenorphine was associated with a lower average withdrawal score (indicating less severe withdrawal) during the treatment episode, with an effect size that is considered to be small to moderate (standardised mean difference (SMD) −0.43, 95% CI −0.58 to −0.28; N = 902; studies = 7; moderate quality). Patients receiving buprenorphine stayed in treatment for longer, with an effect size that is considered to be large (SMD 0.92, 95% CI 0.57 to 1.27; N = 558; studies = 5; moderate quality) and were more likely to complete withdrawal treatment (RR 1.59, 95% CI 1.23 to 2.06; N = 1264; studies = 12; moderate quality). At the same time there was no significant difference in the incidence of adverse effects, but dropout due to adverse effects may be more likely with clonidine (RR 0.20, 95% CI 0.04 to 1.15; N = 134; studies = 3; low quality). The difference in treatment completion rates translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 6), indicating that for every four people treated with buprenorphine, we can expect that one additional person will complete treatment than with clonidine or lofexidine. For studies comparing different rates of reduction of the buprenorphine dose, meta-analysis was possible only for treatment completion, with separate analyses for inpatient and outpatient settings. The results were diverse, and we assessed the quality of evidence as being very low. It remains very uncertain what effect the rate of dose taper has on treatment outcome. Authors' conclusions Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion. Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine. It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research. Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual.

Background There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. Objectives To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence. Search methods The search included the Cochrane Drugs and Alcohol Group's Specialised Register of Trials; the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 5); PubMed (January 1966 to May 2015); EMBASE (Ovid) (January 1974 to May 2015); CINAHL (EBSCOhost) (1982 to May 2015); ISI Web of Science (to May 2014); and PsycINFO (Ovid) (1806 to May 2014). Selection criteria We included randomised controlled trials examining maintenance opioid agonist treatments that made the following two comparisons: 1. full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment and 2. full or partial opioid agonist maintenance versus placebo, detoxification only, or psychological treatment (without opioid agonist treatment). Data collection and analysis We used standard Cochrane methodological procedures. Main results We identified six randomised controlled trials that met inclusion criteria (607 participants). We found moderate quality evidence from two studies of no difference between methadone and buprenorphine in self reported opioid use (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.08 to 1.63) or opioid positive urine drug tests (RR 0.81, 95% CI 0.56 to 1.18). There was low quality evidence from three studies of no difference in retention between buprenorphine and methadone maintenance treatment (RR 0.69, 95% CI 0.39 to 1.22). There was moderate quality evidence from two studies of no difference between methadone and buprenorphine on adverse events (RR 1.10, 95% CI 0.64 to 1.91). We found low quality evidence from three studies favouring maintenance buprenorphine treatment over detoxification or psychological treatment in terms of fewer opioid positive urine drug tests (RR 0.63, 95% CI 0.43 to 0.91) and self reported opioid use in the past 30 days (RR 0.54, 95% CI 0.31 to 0.93). There was no difference on days of unsanctioned opioid use (standardised mean difference (SMD) -0.31, 95% CI -0.66 to 0.04). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on retention in treatment (RR 0.33, 95% CI 0.23 to 0.47). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events (RR 0.19, 95% CI 0.06 to 0.57). The main weaknesses in the quality of the data was the use of open-label study designs. Authors' conclusions There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine appeared equally effective. Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments. Due to the overall low to moderate quality of the evidence and small sample sizes, there is the possibility that the further research may change these findings.

This review considers the effectiveness of drug dependence treatment in preventing HIV transmission among injecting drug users (IDUs). Substitution programmes using agonist pharmacotherapy (e.g. methadone and buprenorphine maintenance treatment) are available only for drug users who are primarily opioid dependent. There are over half a million people in receipt of methadone maintenance treatment (MMT) and it is estimated that this number will double in the coming decade. There is evidence that MMT is associated with a significant decrease in injecting drug use and sharing of injecting equipment. Data on sex-related risk behaviour change are limited, but suggest that MMT is associated with a lower incidence of multiple sex partners or exchanges of sex for drugs or money, but no change, or only small decreases, in unprotected sex. Studies of seroconversion, which is the toughest and most robust standard for assessing the role of MMT in HIV prevention, suggest that the reductions in risk behaviours do translate into actual reductions in cases of HIV infection. While the data on HIV risk behaviour are limited, there is strong evidence that substitution treatment with either methadone or buprenorphine suppresses illicit opioid use. There is also evidence that substitution treatment for HIV-positive IDUs is associated with better compliance with anti-retroviral treatment and improved health outcomes. The only antagonist being used for opioid dependence relapse prevention treatment is naltrexone. There is currently insufficient evidence to draw firm conclusions as to its effectiveness. Behavioural interventions add to the effectiveness of substitution treatment, while the effectiveness of different types of psychological therapy alone has been found to be variable. There have been few comparative studies of abstinence-based treatment, however, available evidence indicates good outcomes for those who remain in treatment for three months or more. All countries with a population of IDUs should aim to develop a comprehensive range of treatments, including substitution treatment, as a critical component of HIV prevention. © 2005 Elsevier B.V. All rights reserved.

Aim: To provide an overview of 5 Cochrane reviews of different approaches for treating opioid withdrawal. Design: Narrative and quantitative summary of review findings. Participants: There were 46 studies included in the original reviews with a total of 3350 participants (range 18–300). Intervention: The 5 reviews considered 46 studies covering seven different comparisons, the major ones being methadone compared with α 2 -adrenergic agonists and other opioid agonists, different α 2 -adrenergic agonists compared with each other and to antagonist-induced withdrawal and buprenorphine. Measurements: The outcomes considered were signs and symptoms of withdrawal, retention in treatment, completion rate, relapse rate and side effects. Findings: Methadone detoxification results in higher retention in treatment, lower relapse rate and fewer side effects when compared with adrenergic agonists. No difference was observed when comparing different adrenergic agonists; buprenorphine appears to have an advantage over adrenergic agonists on withdrawal symptoms and side effects. Conclusions: Despite the considerable number of trials that have been carried out on this topic, they are very heterogeneous as far as the comparisons and outcomes considered. This prevented many of them from being incorporated into a quantitative meta-analysis. Consensus in measurements and results should be reached among researchers involved in the evaluation of the effectiveness of treatments for opiate addiction in order to produce consistent outcomes in the measuring and reporting of results from clinical trials.

To date there has been little consensus on best practice in the management of opioid withdrawal. Regimes involving reducing doses of methadone or the administration of &#102 -adrenergic agonists such as clonidine and lofexidine are most common, but the use of opioid antagonists to induce withdrawal, and the partialagonist, buprenorphine, are gaining in popularity. This paper reviews 213 published reports of interventions to manage opioid withdrawal. Rates of completion and severity of withdrawal are similar when managed with either &#102 -adrenergic agonists or reducing doses of methadone but &#102 -adrenergic agonists, particularly clonidine, are associated with a higher incidence 2 of hypotensive side effects. Variability in the opioid antagonist treatment regimes prevents the identification of standard approaches. The use of opioid antagonists may increase completion rates, but with the risk of more severe withdrawal. Buprenorphine has considerable promise for the management of opioid withdrawal, being...

Injecting drug use is a major risk factor for the acquisition and transmission of the human immunodeficiency virus (HIV) and accounts for approximately 5 to 10% of all cases of HIV infection in the world. People who inject drugs are vulnerable to infection with HIV and other blood-borne viruses, predomi-nantly as a result of the collective use of injecting equipment and, to a lesser extent, of unprotected sexual behaviour.

A 39 year old woman started injecting heroin when she was 18 but soon found she could not control her drug intake or her life in general. At age 30, she sought help and did well with methadone treatment, taking no illicit drugs for three years. However, she then relapsed to heroin use and spent a year in prison, where she continued to inject heroin. After being released, she went to a residential rehabilitation centre. Subsequently in the community her general practitioner started her on buprenorphine. Her life became more stable. She did well with buprenorphine treatment for a few years but restarted injecting heroin after stopping buprenorphine. She restarted buprenorphine and now takes no non-prescribed medication. She works as a waitress and lives with her non-drug using partner. This article is intended for practitioners who occasionally manage patients with opioid dependence. Methadone, a mu opioid agonist, and buprenorphine, a partial agonist, are the main drug treatments for dependence on opioids (which include heroin, morphine, and oxycodone, as well as the other pharmaceutical opioids1 2) for detoxification, maintenance, and ultimately abstinence. Treatment with maintenance goals is referred to as opioid substitution treatment or opioid agonist pharmacotherapy.3 Such treatment is reserved for patients with clearly established opioid dependence and prolonged daily opioid use (by either smoking or injecting). In some countries the combination of buprenorphine and naloxone is preferred (and is now becoming available as a film taken sublingually). Prescription heroin, known in the United Kingdom as heroin assisted treatment or injectable opiate treatment, is used in some countries but is not discussed in this article.4 5 6 Naltrexone blocks the effects of heroin on the mu receptor,2 but oral naltrexone treatment has had low adherence and high discontinuity rates.7 8 Use of naltrexone in the …

This review, funded by the U.K Department for International Development, provides an understanding of the gaps and opportunities for improving access to drug treatment, in particular opioid substitution treatment (OST), for drug users affected and infected by HIV. OST is effective in treating opioid dependency, reducing its individual and social costs. For HIV-infected, opioid-dependent injecting drug users, consistent participation in OST is associated with a higher probability of antiretroviral treatment and, amongst antiretroviral users, more consistent use of antiretrovirals. At the global policy level, there are few barriers to the introduction and expansion of OST with both methadone and buprenorphine now on the WHO Essential Drugs List, and all relevant international organisations approving and encouraging the use of OST for HIV prevention, treatment, care and support in countries where injecting drug use and HIV are found. Unfortunately, there are huge disparities in access to drug treatment, with participation in treatment in Asia and Africa being disturbingly low. Country reports from Vietnam, Kyrgyzstan and Kenya provide examples of the barriers and successes on the ground. Recommendations for donors, international organizations and public health champions include:1. Strengthen leadership at global level for access to drug treatment and, in particular, opioid substitution therapy as a key intervention in HIV prevention, treatment and care among injecting drug users. 2. Develop audit tools for donors to ensure that consideration of harm reduction interventions, prioritizing OST and needle-syringe programmes, becomes a standard part of all development work related to HIV/AIDS. 3. Support the implementation of drug treatment and, in particular, OST in country. 4. Integrate drug treatment and, in particular, OST with HIV treatment. 5. Establish comparable drug treatment programs within correctional institutions to those in the community.

This review summarizes current research on the management of opioid withdrawal and considers the selection of the approach in different situations.The recent publication of three controlled trials makes firm conclusions about the relative effectiveness of newer approaches (antagonist-induced withdrawal under anaesthesia or with minimal sedation; buprenorphine) to the management of opioid withdrawal possible.Antagonist-induced withdrawal under anaesthesia should not be pursued as it has an increased risk of life-threatening adverse events and has no additional benefits relative to antagonist-induced withdrawal under minimal sedation. Antagonist-induced withdrawal with minimal sedation is feasible and may be suitable for those who intend to enter antagonist-maintenance treatment with a clear commitment to abstinence and good support. Buprenorphine is suitable for quick withdrawal, supports transition to naltrexone maintenance treatment, is safe and effective in outpatient settings and can be extended into maintenance treatment if the detoxification attempt is unsuccessful. Adrenergic agonists (clonidine and lofexidine) remain an effective option for those who do not want to use an opioid and do not intend to transfer to naltrexone maintenance treatment, with lofexidine being preferable for outpatient settings. Through appropriate choice of approach, detoxification can be a gateway to multiple, long-term treatment options.

BACKGROUND: Managed withdrawal is a necessary step prior to drug‐free treatment or as the endpoint of substitution treatment. OBJECTIVES: To assess the effects of buprenorphine versus tapered doses of methadone, alpha(2)‐adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha(2)‐adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine‐based regimens. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction. For the comparison of buprenorphine and methadone in tapered doses, meta‐analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to ameliorate opioid withdrawal, without clinically significant adverse effects. The meta‐analyses that were possible support a conclusion of no difference between buprenorphine and methadone in terms of average treatment duration (mean difference (MD) 1.30 days, 95% confidence interval (CI) −8.11 to 10.72; N = 82; studies = 2; low quality) or treatment completion rates (risk ratio (RR) 1.04, 95% CI 0.91 to 1.20; N = 457; studies = 5; moderate quality). Relative to clonidine or lofexidine, buprenorphine was associated with a lower average withdrawal score (indicating less severe withdrawal) during the treatment episode, with an effect size that is considered to be small to moderate (standardised mean difference (SMD) −0.43, 95% CI −0.58 to −0.28; N = 902; studies = 7; moderate quality). Patients receiving buprenorphine stayed in treatment for longer, with an effect size that is considered to be large (SMD 0.92, 95% CI 0.57 to 1.27; N = 558; studies = 5; moderate quality) and were more likely to complete withdrawal treatment (RR 1.59, 95% CI 1.23 to 2.06; N = 1264; studies = 12; moderate quality). At the same time there was no significant difference in the incidence of adverse effects, but dropout due to adverse effects may be more likely with clonidine (RR 0.20, 95% CI 0.04 to 1.15; N = 134; studies = 3; low quality). The difference in treatment completion rates translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 6), indicating that for every four people treated with buprenorphine, we can expect that one additional person will complete treatment than with clonidine or lofexidine. For studies comparing different rates of reduction of the buprenorphine dose, meta‐analysis was possible only for treatment completion, with separate analyses for inpatient and outpatient settings. The results were diverse, and we assessed the quality of evidence as being very low. It remains very uncertain what effect the rate of dose taper has on treatment outcome. AUTHORS' CONCLUSIONS: Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion. Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine. It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research. Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual.

Risks for drug users and the wider community are substantially reduced Prevention of HIV is one of the more persuasive public health arguments in favour of opioid substitution treatment. However, until now, there has been no quantitative estimate of the extent to which this treatment reduces the transmission of HIV. This knowledge gap has been filled by the findings of a linked systematic review by MacArthur and colleagues (doi:10.1136/bmj.e5945).1 This analysis of data from nine studies that included 819 incident HIV infections over 23 608 person years of follow-up found that treatment with methadone was associated with a 54% reduction in the risk of HIV infection among people who inject drugs. An earlier systematic review found that opioid substitution treatment with methadone or buprenorphine is associated with reductions in behaviours associated with a high risk of HIV transmission,2 but owing to methodological limitations, overall estimates of the extent of reduction of these risk behaviours were not calculated. Individual studies were consistent in their findings of reductions of illicit opioid use (ranging from 32% to 69%), injecting drug use (20-60%), and sharing of injecting equipment (25-86%). Treatment …

Background Injecting drug users are vulnerable to infection with Human Immunodeficiency Virus (HIV) and other blood borne viruses as a result of collective use of injecting equipment as well as sexual behaviour Objectives To assess the effect of oral substitution treatment for opioid dependent injecting drug users on risk behaviours and rates of HIV infections\ Search strategy We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO toMay 2011. We also searched reference lists of articles, reviews and conference abstracts Selection criteria Studies were required to consider the incidence of risk behaviours, or the incidence of HIV infection related to substitution treatment of opioid dependence. All types of original studies were considered. Two authors independently assessed each study for inclusion Data collection and analysis Two authors independently extracted key information from each of the included studies. Any differences were resolved by discussion or by referral to a third author. Main results Thirty-eight studies, involving some 12,400 participants, were included. The majority were descriptive studies, or randomisation processes did not relate to the data extracted, and most studies were judged to be at high risk of bias. Studies consistently show that oral substitution treatment for opioid-dependent injecting drug users with methadone or buprenorphine is associated with statistically significant reductions in illicit opioid use, injecting use and sharing of injecting equipment. It is also associated with reductions in the proportion of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but has little effect on condom use. It appears that the reductions in risk behaviours related to drug use do translate into reductions in cases of HIV infection. However, because of the high risk of bias and variability in several aspects of the studies, combined totals were not calculated. Authors' conclusions Oral substitution treatment for injecting opioid users reduces drug-related behaviours with a high risk of HIV transmission, but has less effect on sex-related risk behaviours. The lack of data from randomised controlled studies limits the strength of the evidence presented in this review.