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1.  Harm reduction 
Journal of food and drug analysis  2013;21(4):S10-S12.
The “Harm Reduction” session was chaired by Dr. Jacques Normand, Director of the AIDS Research Program of the U.S. National Institute on Drug Abuse. The three presenters (and their presentation topics) were: Dr. Don Des Jarlais (High Coverage Needle/Syringe Programs for People Who Inject Drugs in Low and Middle Income Countries: A Systematic Review), Dr. Nicholas Thomson (Harm Reduction History, Response, and Current Trends in Asia), and Dr. Jih-Heng Li (Harm Reduction Strategies in Taiwan).
doi:10.1016/j.jfda.2013.09.022
PMCID: PMC4179238  PMID: 25278732
Harm reduction; methadone; Needle/Syringe Programs
2.  Systematic review research on needle/syringe programs and opiate substitution programs in low- and middle-income countries 
Journal of food and drug analysis  2013;21(4):S59-S61.
Persons who inject drugs (PWID) are at an elevated risk for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. In many high-income countries, needle and syringe exchange programs (NSPs) have been associated with reductions in blood-borne infections. However, we do not have a good understanding of the effectiveness of NSP in low/middle-income and transitional-economy countries. A systematic literature review based on PRISMA guidelines was utilized to collect primary study data on coverage of NSP programs and changes in HIV and HCV infection over time among PWID in low- and middle-income and transitional countries (LMICs). Included studies reported laboratory measures of either HIV or HCV and at least 50% coverage of the local injecting population (through direct use or through secondary exchange). We also included national reports on newly reported HIV cases for countries that had national level data for PWID in conjunction with NSP scale-up and implementation. Studies of 11 NSPs with high-coverage from Bangladesh, Brazil, China, Estonia, Iran, Lithuania, Taiwan, Thailand, and Vietnam were included in the review. In five studies, HIV prevalence decreased (range −3% to −15%) and in three studies HCV prevalence decreased (range −4.2% to −10.2%). In two studies, HIV prevalence increased (range +5.6% to +14.8%). HCV incidence remained stable in one study. Of the four national reports of newly reported HIV cases, three reported decreases during NSP expansion, ranging from −30% to −93.3%, whereas one national report documented an increase in cases (+37.6%). Estimated incidence among new injectors decreased in three studies, with reductions ranging from −11/100 person years at risk to −16/100 person years at risk. While not fully consistent, the data generally support the effectiveness of NSP in reducing HIV and HCV infection in low/middle-income and transitional-economy countries. If high coverage is achieved, NSP appear to be as effective in LMICs as in high-income countries. Additional monitoring and evaluation research is needed for NSPs where reductions in HIV/HCV infection among PWID are not occurring in order to identify and correct contributing problems.
doi:10.1016/j.jfda.2013.09.035
PMCID: PMC4176926  PMID: 25267887
HIV; Hepatitis C; needle and syringe programs; opiate substitution programs; low and middle income countries
3.  Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users 
Background
TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.
Materials and methods
A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.
Results
The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors – 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p = 0.037 and 80% vs. 53%; p = 0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR = 0.29, 95% CI = 0.09–0.90). This association remained significant (OR = 0.25, 95% CI = 0.07–0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).
Conclusions
The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.
doi:10.1016/j.meegid.2013.08.008
PMCID: PMC4001117  PMID: 23962581
TLR3; Leu412Phe; Intravenous drug users; Highly exposed HIV seronegatives
4.  The incidence and prevalence of hepatitis C in prisons and other closed settings: Results of a systematic review and meta-analysis 
Hepatology (Baltimore, Md.)  2013;58(4):1215-1224.
People detained in prisons and other closed settings are at elevated risk of infection with hepatitis C virus (HCV). We undertook a systematic review and meta-analysis with the aim of determining the rate of incident HCV infection and the prevalence of anti-HCV among detainees of closed settings. We systematically searched databases of peer-reviewed literature and widely distributed a call for unpublished data. We calculated summary estimates of incidence and prevalence among general population detainees and detainees with a history of injecting drug use (IDU), and explored heterogeneity through stratification and meta-regression. The summary prevalence estimates were used to estimate the number of anti-HCV positive prisoners globally. HCV incidence among general detainees was 1·4 per 100 person-years (py; 95% CI: 0·1, 2·7; k=4), and 16·4 per 100py (95% CI: 0·8, 32·1; k=3) among detainees with a history of IDU. The summary prevalence estimate of anti-HCV in general detainees was 26% (95% CI: 23%, 29%; k=93), and in detainees with a history of IDU, 64% (95% CI: 58%, 70%; k=51). The regions of highest prevalence were Central Asia (38%; 95% CI 32%, 43%; k=1) and Australasia (35%; 95% CI: 28%, 43%; k=9). We estimate that 2·2 million (range: 1·4 million – 2·9 million) detainees globally are anti-HCV positive, with the largest populations in North America (668,500; range: 553,500–784,000) and East and Southeast Asia (638,000; range: 332,000–970,000).
Conclusion
HCV is a significant concern in detained populations, with one in four detainees anti-HCV positive. Epidemiological data on the extent of HCV infection in detained populations is lacking in many countries. Greater attention towards prevention, diagnosis and treatment of HCV infection among detained populations is urgently required.
doi:10.1002/hep.26387
PMCID: PMC3723697  PMID: 23504650
epidemiology; people who inject drugs; prisoners; injecting drug use; viral hepatitis
5.  Prescription opioid misuse and its relation to injection drug use and hepatitis C virus infection: protocol for a systematic review and meta-analysis 
Systematic Reviews  2014;3:95.
Background
The production, prescription, and consumption of opioid analgesics to treat non-cancer pain have increased dramatically in the USA in the past decade. As a result, misuse of these opioids has increased; overdose and transition to riskier forms of drug use have also emerged. Research points to a trend in transition to drug injection among those misusing prescription opioids, where clusters of acute hepatitis C virus (HCV) infection are now being reported. This systematic review and meta-analysis aims to synthesize the prevalence of prescription opioid misuse in the USA and examine the rate of transition to injection drug use and incident HCV in these new people who inject drugs (PWID).
Methods/design
Eligible studies will include quantitative, empirical data including national survey data. Scientific databases will be searched using a comprehensive search strategy; proceedings of scientific conferences, reference lists, and personal communications will also be searched. Quality ratings will be assigned to each eligible report using the Newcastle-Ottawa Scale. Pooled estimates of incidence rates and measures of association will be calculated using random effects models. Heterogeneity will be assessed at each stage of data synthesis.
Discussion
A unique typology of drug use is emerging which is characterized by antecedent prescription opioid misuse among PWID. As the epidemic of prescription opioid misuse matures, this will likely serve as a persistent source of new PWID. Persons who report a recent transition to drug injection are characterized by high rates of HCV seroincidence of 40 per 100 person years or higher. Given the potential for the persistence and escalation of the consequences of prescription opioid misuse in the USA, there is a critical need for synthesis of the current state of the epidemic in order to inform future public health interventions and policy.
Systematic review registration
PROSPERO CRD42014008870.
doi:10.1186/2046-4053-3-95
PMCID: PMC4158728  PMID: 25178433
Prescription opioid misuse; Initiation of injection drug use; Epidemiology; Hepatitis C; Systematic review
6.  Motivational Interviewing to Enhance Nicotine Patch Treatment for Smoking Cessation among Homeless Smokers: A Randomized Controlled Trial 
Addiction (Abingdon, England)  2013;108(6):1136-1144.
AIMS
To assess the effects of adding motivational interviewing (MI) counseling to nicotine patch for smoking cessation among homeless smokers.
DESIGN
Two-group randomized controlled trial with 26-week follow-up.
PARTICIPANTS AND SETTING
430 homeless smokers from emergency shelters and transitional housing units in Minneapolis/St. Paul, Minnesota, USA.
INTERVENTION AND MEASUREMENTS
All participants received 8-week treatment of 21mg nicotine patch. In addition, participants in the intervention group received six individual sessions of MI counseling which aimed to increase adherence to nicotine patch and to motivate cessation. Participants in the Standard Care control group received one session of brief advice to quit smoking. Primary outcome was seven-day abstinence from cigarette smoking at 26 weeks as validated by exhaled carbon monoxide and salivary cotinine.
FINDINGS
Using intention-to-treat analysis, verified seven-day abstinence rate at week 26 for the intervention group was non-significantly higher than for the control group (9.3% vs. 5.6%, p=0.15). Among participants that did not quit smoking, reduction in number of cigarettes from baseline to week 26 was equally high in both study groups (−13.7 ±11.9 for MI vs. −13.5 ±16.2 for Standard Care).
CONCLUSIONS
Adding motivational interviewing counseling to nicotine patch did not significantly increase smoking rate at 26-week follow-up for homeless smokers.
doi:10.1111/add.12140
PMCID: PMC3651796  PMID: 23510102
7.  Smoking Characteristics and Comorbidities in the Power To Quit Randomized Clinical Trial for Homeless Smokers 
Nicotine & Tobacco Research  2012;15(1):22-28.
Introduction:
Smoking prevalence in homeless populations is strikingly high (∼70%); yet, little is known about effective smoking cessation interventions for this population. We conducted a community-based clinical trial, Power To Quit (PTQ), to assess the effects of motivational interviewing (MI) and nicotine patch (nicotine replacement therapy [NRT]) on smoking cessation among homeless smokers. This paper describes the smoking characteristics and comorbidities of smokers in the study.
Methods:
Four hundred and thirty homeless adult smokers were randomized to either the intervention arm (NRT + MI) or the control arm (NRT + Brief Advice). Baseline assessment included demographic information, shelter status, smoking history, motivation to quit smoking, alcohol/other substance abuse, and psychiatric comorbidities.
Results:
Of the 849 individuals who completed the eligibility survey, 578 (68.1%) were eligible and 430 (74.4% of eligibles) were enrolled. Participants were predominantly Black, male, and had mean age of 44.4 years (S D = 9.9), and the majority were unemployed (90.5%). Most participants reported sleeping in emergency shelters; nearly half had been homeless for more than a year. Nearly all the participants were daily smokers who smoked an average of 20 cigarettes/day. Nearly 40% had patient health questionnaire-9 depression scores in the moderate or worse range, and more than 80% screened positive for lifetime history of drug abuse or dependence.
Conclusions:
This study demonstrates the feasibility of enrolling a diverse sample of homeless smokers into a smoking cessation clinical trial. The uniqueness of the study sample enables investigators to examine the influence of nicotine dependence as well as psychiatric and substance abuse comorbidities on smoking cessation outcomes.
doi:10.1093/ntr/nts030
PMCID: PMC3611988  PMID: 22589422
8.  HOSPITAL- VERSUS COMMUNITY–BASED SYRINGE EXCHANGE: A RANDOMIZED CONTROLLED TRIAL 
This study examined the effect of syringe exchange program setting on the injection practices, health status, and health service utilization patterns of injection drug users (IDUs) recruited from a public urban hospital. One hundred sixty-six participants were randomized to either community– or hospital–based syringe exchange services. Poisson regression models were used to compare service utilization between groups. In both conditions, risky drug use practices decreased, and physical health functioning improved over time. Hospital–based syringe exchange program (SEP) attendees had 83% more inpatient admissions (p < .0001) and 22% more ambulatory care visits (p < .0001) than those assigned to the community–based SEP condition. Syringe exchange services that are integrated into public hospital settings may serve as a valuable strategy to engage hard to reach IDU populations in behavioral interventions designed to reduce HIV risk transmission behaviors and increase access to, or engagement in, the use of secondary and tertiary preventive medical care.
doi:10.1521/aeap.2007.19.2.97
PMCID: PMC3853200  PMID: 17411413
9.  Role of sexual transmission of HIV among young non-injection and injection opiate users: A respondent driven sampling study 
Sexually transmitted diseases  2011;38(12):1161-1166.
Background
Little research has investigated sexual transmissibility of HIV among young drug users in China. The objective of this study was to examine the role of sexual transmission on HIV infection among injection drug users (IDUs) and non-injection drug users (NIDUs).
Methods
Respondent-driven sampling (RDS) was used to recruit 426 young heroin/opium drug users in Yunnan, China. Logistic regression modeling was performed to examine interrelationships among risky sexual behaviors, drug-use modes, and drug-use practices.
Results
Substantial proportions of NIDUs and IDUs reported engagement in risky sexual behaviors including: (1) multiple sexual partners (42% of NIDUs vs. 37% of IDUs); (2) concurrent sexual partnerships (48% vs. 46%); (3) commercial sex partners (23% vs. 24%) and sex partners who were NIDUs (14% vs. 17 %). Both NIDUs and IDUs reported low levels of condom use with non-regular partners (48% vs. 42%) and regular partner (24% vs. 27%), and having a history of recent methamphetamine use (21% vs. 18%). Compared to IDUs, NIDUs reported having had fewer sex partners who were IDUs, fewer IDU network peers, more NIDU network peers, and having lower levels of HIV knowledge and self-perceived HIV risk.
Conclusions
Generalization of the HIV epidemic from high-risk groups to the general population may be driven by risky sexual behavior among drug users. Reducing sexual transmission of HIV among both IDUs and NIDUs is the next major challenge for HIV intervention among drug users in China.
doi:10.1097/OLQ.0b013e3182315772
PMCID: PMC3229029  PMID: 22082729
HIV; Injection drug use; Non-Injection drug use; Sexual behavior; China
10.  The epidemiology of viral hepatitis among people who inject drugs: Results of global systematic reviews 
Lancet  2011;378(9791):571-583.
Background
Injecting drug use (IDU) is an important risk for viral hepatitis transmission. Detailed, transparent estimates of the scale of the problem at regional and global levels have never been made. We report national, regional and global prevalence and population size estimates for hepatitis C (HCV) and hepatitis B (HBV) among people who inject drugs.
Methods
Systematic search of peer-reviewed (Medline/Embase/PsycINFO) and grey literature databases, conference abstracts and online resources, with a widely distributed call for additional data. From 4386 peer-reviewed and 1019 grey literature sources, 1125 were reviewed in full. Studies were extracted to a customised database and graded according their methods. Serological reports of HCV antibodies/anti-HCV, HBV antibodies/anti-HBc, and/or HBV surface antigen/HBsAg among IDUs samples with n>40 participants, <100% HIV-positive, and sampling frames that did not exclude participants on the basis of age or sex were included. Using endorsed decision rules, prevalence estimates were calculated with anti-HCV and anti-HBV as proxies for exposure and HBsAg for current infection. These were combined with IDU population sizes to estimate the number of HBV and HCV positive IDUs.
Findings
Eligible reports of anti-HCV among IDUs were located for 77 countries. Prevalence was 60–80% in 26 countries and >80% in 12. We estimate worldwide about 10.0 million (range 6.0–15.2M) IDUs might be anti-HCV positive. China, (1.6M), the USA (1.5M) and the Russian Federation (1.3M) had by far the largest such populations. HBsAg reports were found for 59 countries, ranging from 5–10% in 21 countries and over 10% in 10. Worldwide, 6.4 million IDU might be anti-HBc positive (2.3–9.7M), and 1.2 million (0.3–2.7M) HBsAg positive.
Interpretation
The prevalence of anti-HCV among IDUs is far greater than HIV. Viral hepatitis clearly poses a challenge to public health. Variation in the coverage and quality of existing research creates uncertainty around estimates. Better and more complete data and reporting are required to estimate the scale of the problem, to inform efforts to prevent and treat HCV and HBV among IDUs.
doi:10.1016/S0140-6736(11)61097-0
PMCID: PMC3285467  PMID: 21802134
11.  HCV-Specific T-Cell Immune Responses in Seronegative Injection Drug Users 
Journal of viral hepatitis  2008;16(1):10-20.
Background/Aims
T-cell responses to HCV antigens have been reported in high-risk HCV seronegative persons, suggesting that an effective cellular immune response might be able to clear infection without the development of antibodies. Such findings, however, could be explained by waning antibody or cross-reactivity to other antigens. To address these issues, we assessed T-cell responses in high-risk, seronegative, young IDUs to multiple peptide mixes spanning the entire HCV genome.
Methods
We evaluated HCV-specific T-cell responses in 26 young (age 18-33 years) aviremic, seronegative IDUs (median duration of injection, 6 years) by interferon-γ ELISpot assay using 429 overlapping HCV peptides pooled in 21 mixes. Seventeen aviremic, seropositive IDUs (spontaneous resolvers) and 15 healthy people were used as positive and negative controls, respectively.
Results
The percentage of patients with HCV-specific cellular immune responses was similar in seronegative and seropositive aviremic IDUs (46% versus 59%, p=0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, 6 (23%) had intermediate to very strong responses to 10-20 peptide mixes and another 6 (23%) had moderately strong responses to 2 to 6 mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographic and behavioral risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs. 0.26, p <0.01).
Conclusions
HCV-specific T-cell responses are common among high-risk, seronegative IDUs. The responses are broad and are associated with risk factors for HCV exposure, suggesting that they reflect true exposure to HCV in seronegative persons.
doi:10.1111/j.1365-2893.2008.01016.x
PMCID: PMC2997348  PMID: 18647233
12.  Should Pharmacists have a Role in Harm Reduction Services for IDUs? A Qualitative Study in Tallinn, Estonia 
Despite the high number of injecting drug users (IDUs) in Estonia, little is known about involving pharmacies into human immunodeficiency virus (HIV) prevention activities and potential barriers. Similarly, in other Eastern European countries, there is a need for additional sources for clean syringes besides syringe exchange programmes (SEPs), but data on current practices relating to pharmacists’ role in harm reduction strategies is scant. Involving pharmacies is especially important for several reasons: they have extended hours of operation and convenient locations compared to SEPs, may provide access for IDUs who have avoided SEPs, and are a trusted health resource in the community. We conducted a series of focus groups with pharmacists and IDUs in Tallinn, Estonia, to explore their attitudes toward the role of pharmacists in HIV prevention activities for IDUs. Many, but not all, pharmacists reported a readiness to sell syringes to IDUs to help prevent HIV transmission. However, negative attitudes toward IDUs in general and syringe sales to them specifically were identified as important factors restricting such sales. The idea of free distribution of clean syringes or other injecting equipment and disposal of used syringes in pharmacies elicited strong resistance. IDUs stated that pharmacies were convenient for acquiring syringes due to their extended opening hours and local distribution. IDUs were positive toward pharmacies, although they were aware of stigma from pharmacists and other customers. They also emphasized the need for distilled water and other injection paraphernalia. In conclusion, there are no formal or legislative obstacles for providing HIV prevention services for IDUs at pharmacies. Addressing negative attitudes through educational courses and involving pharmacists willing to be public health educators in high drug use areas would improve access for HIV prevention services for IDUs.
doi:10.1007/s11524-009-9400-5
PMCID: PMC2791822  PMID: 19921542
Injecting drug users; Pharmacists; Harm reduction services
13.  High-prevalence and high-estimated incidence of HIV infection among new injecting drug users in Estonia: need for large scale prevention programs 
Objective
To examine HIV risk behavior and HIV infection among new injectors in Tallinn, Estonia.
Design and methods
Data from two cross-sectional surveys of injecting drug users (IDUs) recruited from a syringe exchange program (N = 162, Study 1) or using respondent driven sampling (N = 350, Study 2). Behavioral surveys were administered; serum samples were collected for HIV testing. Subjects were categorized into new injectors (injecting ≤ 3 years) and long-term injectors (injecting > 3 years).
Results
Twenty-eight of 161 (17%, Study 1) and 73/350 (21%, Study 2) of the study subjects were new injectors. HIV infection was substantial among the newer injectors: HIV prevalence was 50% (Study 1) and 34% (Study 2), and estimated HIV incidence 31/100 PY and 21/100 PY, respectively. In Study 2, new injectors were more likely to be female and ethnic Estonian and less likely to be injecting daily compared with long-term injectors. No significant difference was found among two groups on sharing injecting equipment or reported number of sexual partners.
Conclusions
A continuing HIV epidemic among new injectors is of critical public health concern. Interventions to prevent initiation into injecting drug use and scaling up HIV prevention programs for IDUs in Estonia are of utmost importance.
doi:10.1093/pubmed/fdn014
PMCID: PMC2925676  PMID: 18308743
Estonia; HIV; IDU; injection drug use; new injecting drug users
14.  Exploring drug users’ attitudes and decisions regarding hepatitis C (HCV) treatment in the U.S 
Individuals with a history of injecting drugs are at the highest risk of becoming infected with the hepatitis C virus (HCV), with studies of patients in methadone maintenance treatment programmes (MMTPs) reporting that 60–90% of intravenous drug users (IDUs) have the virus. Fortunately, HCV therapy has been shown to be effective in 42–82% of all patients with chronic HCV infection, including IDUs. While the decision to start HCV therapy requires significant consideration, little research exists that explores the attitudes of drug users toward HCV therapy. Therefore, this paper examines how drug users perceive the treatment, as well as the processes by which HCV-positive individuals examined the advantages and disadvantages of starting the HCV medications. Interviews were conducted with 164 patients from 14 drug treatment programmes throughout the United States, and both uninfected and HCV-positive drug users described a pipeline of communication among their peers that conveys largely negative messages about the medications that are available to treat HCV. Although many of the HCV-positive individuals said that these messages heightened their anxiety about the side effects and difficulties of treatment, some patients said that their peers helped them to consider and/or initiate HCV treatment. Gaining a better understanding of drug users’ perceptions of HCV treatment is important, because so many of them, particularly IDUs, are already infected with HCV and may benefit from support in addressing their HCV treatment needs. In addition, currently uninfected drug users will likely remain at high risk for contracting HCV and may need to make decisions about whether or not to start the HCV medical regimen in the future.
doi:10.1016/j.drugpo.2007.02.003
PMCID: PMC2698452  PMID: 18312822
hepatitis C; substance abuse; drug treatment programmes; medical treatment

Results 1-14 (14)