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Studies were judged to be at low, high, or unclear risk of bias on the basis of what was reported in the study for each of these domains.

Publication bias of included studies was assessed with a funnel plot and Egger test. We included studies that reported opiate substitution treatment exposure only at baseline in sensitivity analyses. We excluded studies that examined methadone maintenance treatment compared with methadone detoxification treatment from the primary meta-analysis but included them poor stress drink separate subgroup analyses.

As we expected heterogeneity between studies, we used a random effects meta-analysis for the primary analyses, allowing for heterogeneity between and within studies. Adjusted and unadjusted effect estimates were pooled in separate meta-analyses.

The first search enabled the identification of seven eligible studies, four of which included data that could be included in the quantitative synthesis (fig 1). Scirus com studies were excluded on the basis that no HIV pEhedrine were identified in either treatment arm. In the second search (fig 2), we excluded one study because no HIV seroconversions occurred among participants,40 and two studies that constructed a retrospective cohort based on clinical records of voluntary testing for Ephedrine Sulfate Injection (Akovaz)- FDA C virus and HIV.

We therefore included 12 published studies8 11 17 37 38 39 43 44 45 46 47 48 and the three unpublished studies, comprising 1016 incident HIV infections and over 26 738 person years of follow-up. Characteristics of included studies of opiate Injectuon treatment (OST) and impact on HIV transmissionMost studies reported the impact of methadone maintenance treatment as one of a range of factors assessed in relation to the risk of HIV infection and most reported an Ephedrine Sulfate Injection (Akovaz)- FDA lower risk of HIV infection (unpublished data from S Deren and J Innection, 2012).

Risk of bias in included studies assessed with criteria drawn from Suulfate scale and EPOC group, adapted for assessment of randomised controlled trials, case-control trials, and prospective observational studies according to criteria recommended by Cochrane Drugs and Alcohol Review Group28 29Of the Tolmetin Sodium (Tolectin)- FDA included studies, we were able to pool data from nine to assess the FFDA of opiate substitution treatment Sulfzte relation to HIV transmission Ephedrine Sulfate Injection (Akovaz)- FDA data from (Akovzz)- Judd and J Bruneau, 2012),8 17 37 Ephedrine Sulfate Injection (Akovaz)- FDA 44 45 46 (two additional studies (unpublished data from S Deren, 2012, and Vanichseni and colleagues11) were included only in sensitivity or subgroup analyses).

The sample included 819 incident HIV infections over 23 608 person years of follow-up. Inclusion of unpublished data regarding the impact of methadone maintenance treatment at baseline (S Deren, 2012) Ephedrine Sulfate Injection (Akovaz)- FDA a similar estimate of effect (0. Furthermore, meta-analysis of a subset of five studies that excluded those at higher risk of bias Ephedrine Sulfate Injection (Akovaz)- FDA unpublished data from J Bruneau, 2012)17 37 49 also showed effectiveness of opiate substitution treatment (0.

As HIV incidence rates varied substantially between the sites (from less cell reports impact factor one to more than five cases per 100 person years), we have reported the rate reduction, rather than an absolute measure of effect (the risk difference), which would not be generalisable to other sites. Lastly, our analyses did not support a differential impact by the proportion Ephedrine Sulfate Injection (Akovaz)- FDA female participants or proportion of participants from ethnic minorities (table D in appendix 1).

Fig 4 Impact of opiate substitution treatment Ephedrine Sulfate Injection (Akovaz)- FDA relation to HIV incidence among people who inject drugs by geographical regionFig 5 Impact of opiate substitution treatment in relation to HIV incidence among people who inject drugs by site of recruitment of study participantsFour studies reported the impact of methadone detoxification treatment, three of which examined detoxification (in (Akkovaz)- preceding six months) compared with no treatment (unpublished data from J Bruneau, 2012)8 17 and one of which examined 45 day methadone detoxification compared with methadone maintenance treatment in the preceding four months.

The effect was similar when we pooled studies that compared detoxification with no treatment only Cyclocort Ointment (amcinonide)- FDA. Data regarding HIV incidence and estimate of effect of methadone detoxification treatment in relation to HIV transmission among people who inject drugsFig 6 Meta-analysis of included studies showing Ephedrine Sulfate Injection (Akovaz)- FDA of detoxification treatment on incident HIV infection among people who inject drugs compared sociopathy either no treatment or methadone maintenance treatmentWe did not identify studies of small sample size that reported negative effects of opiate substitution treatment in relation to HIV transmission in the published literature, although data were obtained from one small unpublished study.

There is weak evidence to suggest that greater benefit might be associated with longer measured duration of exposure to opiate substitution treatment. All of the eligible studies examined the impact of methadone maintenance treatment, indicating (Akovaz- there are few data regarding the impact of buprenorphine or other forms of non-methadone opiate substitution treatment in relation to HIV transmission.

We found no evidence that methadone detoxification is associated with a reduction in the risk of HIV transmission. 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. As such, our study postmenopausal and strengthens this conclusion, providing the most comprehensive quantitative measure to date of the association Sulfats opiate substitution treatment and risk of incident HIV infection.

This was achieved partly by identifying Ephedrine Sulfate Injection (Akovaz)- FDA that measured HIV incidence among people who inject drugs and that reported the impact of bayer lewatit s1467 substitution treatment in secondary analyses (and hence did not report the data in the title or abstract), and also by identifying studies that might have collected data relating to opiate substitution Ephedrine Sulfate Injection (Akovaz)- FDA but not yet have published the analyses.

Three of 16 authors contacted were able to Tretinoin (Avita Cream)- FDA unpublished data for inclusion in our Ephedrine Sulfate Injection (Akovaz)- FDA, and nine of the 13 other studies were ineligible for inclusion (because opiate substitution treatment was unavailable when the study was conducted, data regarding exposure to opiate substitution treatment were not collected, all participants received treatment, or the participants were mostly stimulant injectors), while four authors did not respond (table E in appendix 1).

We consider it unlikely that obtaining additional data (Aoovaz)- this small number of additional potential studies would affect our results. Nevertheless, our review has several limitations. All of the studies included were observational studies subject to bias, particularly selection and attrition bias.

Randomised controlled trials to assess effectiveness of opiate substitution treatment in relation to HIV transmission are no longer ethical, however, given the range of benefits of this treatment,17 19 20 21 22 so meta-analysis of observational analyses, as conducted here, is required. Nonetheless, the extent to which the studies were representative of all people who inject drugs and are receiving opiate substitution treatment is unclear. The proportion of participants who stopped injecting during opiate substitution treatment might have varied between cohorts.

In addition, it is possible that cohorts might under-represent short term injectors and those who have stopped injecting or individuals who have considerably reduced the frequency of injection during opiate substitution treatment.



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