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      Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta-Analysis

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          Abstract

          This meta-analysis provides strong evidence that opioid substitution therapy improves several key outcomes of the HIV care continuum among people who inject drugs, including recruitment onto antiretroviral therapy, retention in care, adherence, and viral suppression.

          Abstract

          Background.  Human immunodeficiency virus (HIV)–infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID.

          Methods.  We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I 2 statistic.

          Results.  We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32–2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17–2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41–3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63–.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21–1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65–1.25).

          Conclusions.  These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID.

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          HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage.

          Previous reviews have examined the existence of HIV prevention, treatment, and care services for injecting drug users (IDUs) worldwide, but they did not quantify the scale of coverage. We undertook a systematic review to estimate national, regional, and global coverage of HIV services in IDUs. We did a systematic search of peer-reviewed (Medline, BioMed Central), internet, and grey-literature databases for data published in 2004 or later. A multistage process of data requests and verification was undertaken, involving UN agencies and national experts. National data were obtained for the extent of provision of the following core interventions for IDUs: needle and syringe programmes (NSPs), opioid substitution therapy (OST) and other drug treatment, HIV testing and counselling, antiretroviral therapy (ART), and condom programmes. We calculated national, regional, and global coverage of NSPs, OST, and ART on the basis of available estimates of IDU population sizes. By 2009, NSPs had been implemented in 82 countries and OST in 70 countries; both interventions were available in 66 countries. Regional and national coverage varied substantially. Australasia (202 needle-syringes per IDU per year) had by far the greatest rate of needle-syringe distribution; Latin America and the Caribbean (0.3 needle-syringes per IDU per year), Middle East and north Africa (0.5 needle-syringes per IDU per year), and sub-Saharan Africa (0.1 needle-syringes per IDU per year) had the lowest rates. OST coverage varied from less than or equal to one recipient per 100 IDUs in central Asia, Latin America, and sub-Saharan Africa, to very high levels in western Europe (61 recipients per 100 IDUs). The number of IDUs receiving ART varied from less than one per 100 HIV-positive IDUs (Chile, Kenya, Pakistan, Russia, and Uzbekistan) to more than 100 per 100 HIV-positive IDUs in six European countries. Worldwide, an estimated two needle-syringes (range 1-4) were distributed per IDU per month, there were eight recipients (6-12) of OST per 100 IDUs, and four IDUs (range 2-18) received ART per 100 HIV-positive IDUs. Worldwide coverage of HIV prevention, treatment, and care services in IDU populations is very low. There is an urgent need to improve coverage of these services in this at-risk population. UN Office on Drugs and Crime; Australian National Drug and Alcohol Research Centre, University of New South Wales; and Australian National Health and Medical Research Council. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Mortality among people who inject drugs: a systematic review and meta-analysis

            OBJECTIVE: To systematically review cohort studies of mortality among people who inject drugs, examine mortality rates and causes of death in this group, and identify participant- and study-level variables associated with a higher risk of death. METHODS: Tailored search strings were used to search EMBASE, Medline and PsycINFO. The grey literature was identified through online grey literature databases. Experts were consulted to obtain additional studies and data. Random effects meta-analyses were performed to estimate pooled crude mortality rates (CMRs) and standardized mortality ratios (SMRs). FINDINGS: Sixty-seven cohorts of people who inject drugs were identified, 14 of them from low- and middle-income countries. The pooled CMR was 2.35 deaths per 100 person-years (95% confidence interval, CI: 2.12-2.58). SMRs were reported for 32 cohorts; the pooled SMR was 14.68 (95% CI: 13.01-16.35). Comparison of CMRs and the calculation of CMR ratios revealed mortality to be higher in low- and middle-income country cohorts, males and people who injected drugs that were positive for human immunodeficiency virus (HIV). It was also higher during off-treatment periods. Drug overdose and acquired immunodeficiency syndrome (AIDS) were the primary causes of death across cohorts. CONCLUSION: Compared with the general population, people who inject drugs have an elevated risk of death, although mortality rates vary across different settings. Any comprehensive approach to improving health outcomes in this group must include efforts to reduce HIV infection as well as other causes of death, particularly drug overdose.
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              Impact of covert duplicate publication on meta-analysis: a case study.

              To quantify the impact of duplicate data on estimates of efficacy. Systematic search for published full reports of randomised controlled trials investigating ondansetron's effect on postoperative emesis. Abstracts were not considered. Eighty four trials (11,980 patients receiving ondansetron) published between 1991 and September 1996. Percentage of duplicated trials and patient data. Estimation of antiemetic efficacy (prevention of emesis) of the most duplicated ondansetron regimen. Comparison between the efficacy of non-duplicated and duplicated data. Data from nine trials had been published in 14 further reports, duplicating data from 3335 patients receiving ondansetron; none used a clear cross reference. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports not subject to duplicate publication, three reports subject to duplicate publication, and six duplicates of those three reports. The number needed to treat to prevent vomiting within 24 hours was 9.5 (95% confidence interval 6.9 to 15) in the 16 non-duplicated reports and 3.9 (3.3 to 4.8) in the three reports which were duplicated (P < 0.00001). When these 19 were combined the number needed to treat was 6.4 (5.3 to 7.9). When all original and duplicate reports were combined (n = 25) the apparent number needed to treat improved to 4.9 (4.4 to 5.6). By searching systematically we found 17% of published full reports of randomised trials and 28% of the patient data were duplicated. Trials reporting greater treatment effect were significantly more likely to be duplicated. Inclusion of duplicated data in meta-analysis led to a 23% overestimation of ondansetron's antiemetic efficacy.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                15 October 2016
                25 June 2016
                25 June 2016
                : 63
                : 8
                : 1094-1104
                Affiliations
                [1 ]School of Social and Community Medicine, University of Bristol , United Kingdom
                [2 ]ICAP, Columbia University , New York, New York
                [3 ]International HIV/AIDS Alliance , Brighton
                [4 ]Division of Health Research, Lancaster University
                [5 ]School of Clinical Veterinary Sciences, University of Bristol
                [6 ]London School of Hygiene and Tropical Medicine, United Kingdom
                [7 ]University of California, San Diego
                Author notes
                Correspondence: A. J. Low, Mailman School of Public Health, Columbia University, 722 W 168th, 13th Flr, New York, NY 10032 ( andrea_low@ 123456hotmail.com ).
                Article
                ciw416
                10.1093/cid/ciw416
                5036913
                27343545
                749f10ec-94ed-4299-b17f-3a0aaf84efc8
                © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@ 123456oup.com .

                History
                : 17 February 2016
                : 15 June 2016
                Funding
                Funded by: National Institute for Health Research;
                Funded by: International Human Immunodeficiency Virus/AIDS Alliance;
                Funded by: National Institute on Drug Abuse;
                Award ID: R01 DA037773-01A1
                Funded by: National Institute for Health Research Health;
                Funded by: NIHR;
                Funded by: NIHR;
                Funded by: Bill & Melinda Gates Foundation;
                Categories
                HIV/AIDS
                Editor's choice

                Infectious disease & Microbiology
                hiv,people who inject drugs (pwid),medication-assisted therapy for opioid dependence (mat),antiretroviral treatment (art),systematic review

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