Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

AIMS: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months). MEASUREMENTS: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID. FINDINGS: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity. CONCLUSIONS: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration.

Field Testing the "Avoid the Needle" Intervention for Persons at Risk for Transitioning to Injecting Drug Use in Tallinn, Estonia and New York City, USA.

This study aimed to field tested the "Avoid the Needle" (AtN) intervention to reduce transitions from non-injecting to injecting drug use in two different epidemiological settings. Respondent driven sampling was used to recruit current non-injecting drug users (NIDUs) in Tallinn, Estonia in 2018-19 and in New York City (NYC) in 2019-20. Both persons who had never injected and persons who had previously injected but not in the last 6 months were eligible; a structured interview was administered, a blood sample collected, and the intervention administered by trained interventionists. We recruited 19 non-injectors from Tallinn and 140 from NYC. Participants in Tallinn were younger and had begun using drugs at earlier ages than participants in NYC. The primary drugs used in Tallinn were amphetamine, fentanyl, and opioid analgesics, while in NYC they were heroin, cocaine, speedball, and fentanyl. Six-month follow-up data were obtained from 95% of participants in Tallinn. The study was interrupted by COVID-19 lockdown in NYC, but follow-up data were obtained from 59% of participants. There were minimal transitions to injecting: 1/18 in Tallinn and 0/83 in NYC. There were significant declines in the frequencies of using readily injectable drugs (fentanyl, amphetamine, heroin, cocaine) from baseline to follow-up in both sites (Cochran-Armitage tests for trend, χ2 = 21.3, p < 0.001 for New York City; and χ2 = 3.9, p = 0.048 for Tallinn). Reducing transitions into injecting is a potentially very important method for reducing HIV transmission and other harms of drug use. Further investigation and implementation of AtN type interventions is warranted.

A Multistage Process Model of How a Person Who Currently Injects Drugs Comes to Assist Persons Who Do not Inject with Their First Injections.

Injecting drugs for the first time almost always requires assistance from an experienced person who injects drugs (PWID). While there has been moderate amount of research on PWID who assist with first injections, most of this research has focused on identifying characteristics of PWID who assist with first injections. We do not have a formal model that describes how the minority of PWID come to assist do so, while the majority never assist. Through comparison of persons who did or did not recently assist with first injections using data from PWID in Tallinn, Estonia (N = 286) and Staten Island, New York City (N = 101), we developed a formal multi-stage model of how PWID come to assist with first injections. The model had a primary pathway 1) of engaging in "injection promoting" behaviors, 2) being asked to assist, and 3) assisting. Statistical testing using odds ratios showed participation in each stage was strongly associated with participation in the next stage (all odds ratios >3.0) and the probabilities of assisting significantly increased with participation in the successive stages. We then used the model to compare engagement in the stages pre-vs. post participation in an intervention, and to compare persons who recently assisted to persons who had assisted in the past but had not recently assisted and to persons who had never assisted. Advantages of a formal model for how current PWID come to assist with first injections include: facilitating comparisons across different PWID populations and assessing strengths and limitations of interventions to reduce assisting with first injections.

Rapid point-of-care (POC) testing for Hepatitis C antibodies in a very high prevalence setting: persons injecting drugs in Tallinn, Estonia.

BACKGROUND: Between December 2018 and January of 2019, we evaluated the accuracy of the point-of-care Hepatitis C (HCV) antibody test (POC; OraQuick HCV) used at a community-based needle and syringe exchange program serving persons who inject drugs in Tallinn, Estonia. METHODS: We compared the results of screening for HCV antibodies by OraQuick (oral swab) and enzyme immunoassay (EIA; blood draw) and assessed test results implications in a high prevalence setting. Findings Of the 100 participants, 88 (88%) had reactive POC test results, and 93 were HCV antibody positive on EIA testing. Sensitivity, specificity and negative predictive value (NPV) for the POC assay with EIA as the relevant reference test were as follows: 94.6% (95% CI 90.0-99.2%), 100% and 58.3% (95% CI 30.4-86.2%). Of the 12 testing, HCV-negative with the POC only 7 (58.3%) were true negatives. CONCLUSIONS: Oral swab rapid testing HCV screening in this nonclinical setting was sensitive and specific but had unacceptably low NPV. In high prevalence settings, POC tests with high sensitivity and that directly measure HCV RNA may be warranted.

The fentanyl epidemic in Estonia: factors in its evolution and opportunities for a comprehensive public health response, a scoping review.

BACKGROUND: The spread of illicitly manufactured fentanyl has the potential to greatly increase the fatal overdoses in many places in the world. The purpose of this paper is to analyse the evolution of fentanyl use epidemic in Estonia. METHODS: this scoping review is based on extensive review and synthesis of broad range of literature: research reports, newspaper, magazine, coverage of illicit fentanyl use; policy documents, position papers, reports released by government agencies, and surveillance data. RESULTS: For an over a decade up to 2017, Estonia has had the highest overdose death mortality in Europe. The use of (injected) fentanyl is a major contributor to the Estonian overdose death epidemic. Shutting down a major producer and distributor of illicit fentanyl has been extremely effective in curbing the number of overdose deaths. Unfortunately, this supply-side intervention came ten years into the epidemic, and might be difficult to replicate in settings with decentralized production. In areas faced by fentanyl we would recommend large-scale implementation of opiate substitution treatment and naloxone distribution, syringe service programs to provide for safer injecting and link to other services (high frequencies of fentanyl injection create high risk for HIV and HCV transmission), and programs, such as "Break the Cycle," to reduce initiation into injecting drug use. Further, the means of responding to emerging substances should match the world in which different substances can be rapidly introduced, and where people who use drugs can change preferences based on market availability. CONCLUSION: Addressing illicitly manufactured fentanyl may serve as a public health learning experience for developing early detection and rapid response programs in rapidly changing drug use environments.

Implementing an Updated "Break the Cycle" Intervention to Reduce Initiating Persons into Injecting Drug Use in an Eastern European and a US "opioid epidemic" Setting.

We tested the hypothesis that an updated "Break the Cycle" (BtC) intervention, based in social cognitive theory and motivational interviewing, would reduce the likelihood that current persons who inject drugs (PWID) would assist persons who do not inject drugs (non-PWID) with first injections in Tallinn, Estonia and Staten Island, New York City. 402 PWID were recruited, a baseline interview covering demographics, drug use, and assisting non-PWID with first drug injections was administered, followed by BtC intervention. 296 follow-up interviews were conducted 6 months post-intervention. Percentages assisting with first injections declined from 4.7 to 1.3% (73% reduction) in Tallinn (p < 0.02), and from 15 to 6% (60% reduction) in Staten Island (p < 0.05). Persons assisted with first injections declined from 11 to 3 in Tallinn (p = 0.02) and from 32 to 13 in Staten Island. (p = 0.024). Further implementation research on BtC interventions is urgently needed where injecting drug use is driving HIV/HCV epidemics and areas experiencing opioid epidemics.

Frequency and factors associated with providing injection initiation assistance in Tallinn, Estonia.

Injection drug use is expanding in numerous regions in the world. Persons who inject drugs (PWID) play an important role encouraging new persons into injecting, by providing injection initiation assistance ("assisting" behaviors) and stimulating interest in injection ("promoting" behaviors). OBJECTIVES: To describe the prevalence of assisting and promoting behaviors, and to identify factors associated with assisting, among PWID in Tallinn, Estonia. METHODS: In 2016, PWID were recruited through respondent-driven sampling (RDS), interviewed, and HIV tested. RDS weights were used to estimate the prevalence of assisting and promoting behaviors and, in multivariable regression modeling, to identify factors associated with assisting. RESULTS: Among 299 PWID recruited, 13.7% had ever assisted a non-PWID with their first injection. Regarding past-six-month promoting behaviors: 9.4% talked positively about injecting to non-PWID, 16.2% injected in front of non-PWID, and 0.6% offered to help with a first injection. Significant predictors of ever assisting with a first injection included: gender (men: aOR 6.31, 95% CI 2.02-19.74); age (30 years or younger: aOR 3.89, 95% CI 1.40-10.16); receptive sharing of syringes or needles (aOR 4.73, 95% CI 1.32-16.98); ever testing for HIV (aOR 8.44, 95% CI 1.15-62.07); and having peers who helped someone with their first injection (aOR 3.44, 95% CI 1.31-9.03). CONCLUSION: Demographic and drug-use related factors are associated with having initiated someone into injecting. Interventions targeting PWID and non-PWID are needed to prevent injection initiation.

HIV prevalence and gender differences among new injection-drug-users in Tallinn, Estonia: A persisting problem in a stable high prevalence epidemic.

INTRODUCTION: New injectors / younger drug users are an important population to target for intervention because they are often at especially high risk of HIV and HCV infection. We examined HIV prevalence and gender differences in HIV prevalence and risk behavior among new injection-drug-users in Tallinn, Estonia. METHODS: Respondent driven sampling (RDS) interview surveys and HIV testing were conducted in Tallinn in 2009, 2011 and 2013. We classified "new injectors" as persons who reported their first injection as occurring within three years of the study interview. Recruiting trees of the three individual RDS studies were joined to form one RDS dataset and RDS estimates for prevalence and means were derived. Bootstrap tests were used to compare data from men and women, HIV infected and uninfected. RESULTS: Among 110 new injectors (34 women and 76 men) the mean age was 24.5 (SD 7.5) years; 63% reported injecting mainly fentanyl, 34% injecting mainly amphetamine, 36% sharing syringes, 89% were sexually active, and, of these, 88% did not always use condoms in the last 6 months. HIV prevalence was 18% (95%CI 8-28%) (41% (95%CI 19-63%) among female and 7% (95%CI 2-12%) among male new injectors). Based on self-reports, 8.1% of all new injectors (and 22% of female new injectors) were HIV positive before starting to inject drugs. 40% of HIV infected reported receiving antiretroviral therapy. In multivariable analysis, gender (male: OR 0.12, 95% CI 0.03-0.45), main drug injected (fentanyl: OR 6.7, 95% CI 1.3-35.7) and syringe sharing (distributive: OR 0.11, 95% CI 0.02-0.55; and receptive: OR 3.7, 95% CI 1.0-13.5) were associated with the HIV seropositivity. CONCLUSIONS: New injectors exhibit high-risk behavior and correspondingly high HIV prevalence. Sexual transmission of HIV infection, including before injection initiation, is likely to be a significant contributor to HIV risk among female new injectors. This highlights the need to identify and target new injectors and their partners with gender specific interventions in addition to interventions to reduce initiation into injecting and ensuring provision of ART to HIV positive new injectors.

A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

OBJECTIVE: The role of CC chemokine receptor 5 (CCR5) and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID) from Estonia. METHODS: Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D) were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789) typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. RESULTS: Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C) decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40), which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29). An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively) compared to those who did not possess these haplotypes, respectively. CONCLUSIONS: Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.

Post-Soviet Central Asia: a summary of the drug situation.

BACKGROUND: The paper aims to provide a snapshot of the drug situation in Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan using the EU methodology of "harmonised indicators of drug epidemiology." METHODS: Most of the data reported here were gathered and analysed within the framework of the EU-funded CADAP project in 2012. Together with members of CADAP national teams, we conducted extraction from the databases of national institutions in the field of (public) health and law enforcement, issued formal requests for the provision of specific information to national governmental authorities, and obtained national grey literature in Russian. In specific cases, we leaned on the expert opinions of the national experts, gathered by means of simple online questionnaires or focus group. In the rather scarce cases where peer-reviewed sources on the specific topics exist, it is used for comparisons and discussion. RESULTS: All the post-Soviet Central Asian countries lack information on drug use in the general population. School surveys are relatively well developed in Kazakhstan, and Kyrgyzstan benefited from an international survey project on health in schools organised by private donors in 2009. For Tajikistan and Uzbekistan, the most recent available data on drug use in the school population are from 2006 and as such are of little relevance. Problem drug use is widespread in Central Asia and estimates of its prevalence are available for all four countries. All the post-Soviet Central Asian countries use a rather outdated system of narcological registers as the only source of data on drug users who are treated (and those investigated by the police), which was inherited from Soviet times. The availability of treatment is very low in all the countries reported on here except Kyrgyzstan; opioid substitution treatment (OST) was introduced first in Kyrgyzstan; Kazakhstan and Tajikistan are piloting their OST programmes but the coverage is extremely low, and in Uzbekistan the OST pilot programme has been abolished. HIV and hepatitis C virus (HCV) infections are concentrated in injecting drug users (IDUs) in Central Asia, with the situation in Kazakhstan having stabilised; HIV is on the increase among Kyrgyz IDUs. The sharp decrease in HIV and VHC seroprevalence among IDUs in Uzbekistan and Tajikistan still awaits an explanation. The system for monitoring of fatal drug overdoses needs substantial improvement in all the countries reported on here. Overall mortality studies of drug users registered in the narcological registers were performed in Uzbekistan, Kazakhstan, and Tajikistan; the highest excess mortality among registered drug users was found in Uzbekistan, and in all three countries, it was substantially higher for women than men. The seizures of illegal drugs are by far the highest in Kazakhstan; however, wild-growing cannabis represents 90% of these seizures. Uzbekistan was the country with the highest number of drug arrests. In Kazakhstan, after the decriminalisation of drug use in 2011, the number of reported drug-related offences dropped to below 50% of the figure for the previous year. CONCLUSION: The drug situation monitoring system in the four post-Soviet countries of Central Asia still needs substantial improvement. However, in its current state it is already able to generate evidence that is useful for the planning of effective national and regional drug policies, which would be of the utmost importance in the forthcoming years of the withdrawal of the International Security Assistance Force from Afghanistan.

Mortality of registered drug users in Central Asia.

BACKGROUND: Within the fifth phase of the Central Asia Drug Action Programme (CADAP) covering five post-Soviet Central Asian countries, an analysis of the mortality of drug users was performed. The results for Kazakhstan and Uzbekistan are presented in detail in this paper since results from Kyrgyzstan and Tajikistan are not considered valid and Turkmenistan did not provide data at all. METHODS: A system of registration of all users of illegal drugs known to the health and/or law enforcement authorities ("narcological registers") exists in Central Asian countries inherited from the system of Soviet "narcology". According to the legal norms, the death of a registered person should be recorded. We conducted indirect standardisation of crude mortality rates and computed the standardised mortality ratio (SMR) comparing observed number of deaths with expected number of deaths according to age and gender specific mortality rates in the general population of the same country. RESULTS: The results show excess mortality in registered drug users, particularly in registered females, in Uzbekistan (the latest available SMR for all those registered is 7.4; the SMR in females is 16.3) and Kazakhstan (4.0 and 12.9). The excess mortality is highest among young adults (18-34) in all the studies. CONCLUSION: Taking into account the limited quality and reliability of the data - first of all, the likely under-reporting of deaths in the narcological registers - the crude mortality rate among registered drug users is quite high when compared to EU countries. The SMR in total is comparably lower as a result of the high background mortality in the general population. This excess mortality is preventable and should be targeted by the national drug policies. Specifically, the programmes should target registered and unregistered female drug users.

Association between HIV-1 tropism and CCR5 human haplotype E in a Caucasian population.

BACKGROUND: The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population. METHODS: We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping 9 CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the maximum likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution. RESULTS: The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were over represented among people with CCR5 human haplotype E (HHE) compared with those without this haplotype (13.0% vs 1.4%; P = 0.006). People possessing CCR5 HHE had 11 times increased odds (odds ratio = 11.00; 95% confidence interval: 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral (ARV) therapy, neither the presence of HHE nor the use of ARV was associated with X4 tropic viruses. CONCLUSIONS: Our results suggest that CCR5 HHE and ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.

Prevalence of IGRA-positivity and risk factors for tuberculosis among injecting drug users in Estonia and Latvia.

BACKGROUND: Illegal drug use and HIV are independent risk factors for tuberculosis (TB) among injecting drug users (IDU). Estonia and Latvia have experienced high rates of TB as well as IDU and HIV outbreaks. There is a lack of knowledge about TB among IDUs in these countries. The purpose of the current study was to estimate the prevalence and risk factors of Mycobacterium tuberculosis (MTB) infection among IDUs in Estonia and Latvia. METHODS: Participants for this cross-sectional study were recruited from syringe exchange programmes using respondent-driven sampling. For assessing infection with MTB interferon-gamma release assay (IGRA) was used. RESULTS: The study included 375 participants from Estonia and 313 from Latvia. The prevalence of IGRA-positivity among IDUs was 7.7% in Estonia and 25.6% in Latvia. HIV-prevalence was 62% in Estonia and 23% in Latvia. In both countries, IGRA-positivity rates did not differ between HIV-positive and HIV-negative participants. IGRA-positivity was independently associated with a prior diagnosis of TB in Estonia and with imprisonment (ever within a lifetime) and preceding contact with a TB patient in Latvia. CONCLUSION: Our findings indicate there is an urgent need for a more vigorous approach in providing IDUs with TB screening services.

CCR5 haplotypes influence HCV serostatus in Caucasian intravenous drug users.

BACKGROUND: Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia. METHODS: Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2-CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5. RESULTS: Compared to IDUs seronegative for both HCV and HIV (HCV-/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (P(adjusted) = 1.89 × 10(-4) and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% and<10% of HCV-/HIV- IDUs and HCV-/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype. CONCLUSIONS: Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.

A decline in the prevalence of injecting drug users in Estonia, 2005-2009.

AIMS: Here we report a study aimed at estimating trends in the prevalence of injection drug use between 2005 and 2009 in Estonia. BACKGROUND: Descriptions of behavioural epidemics have received little attention compared with infectious disease epidemics in Eastern Europe. METHODS: The number of injection drug users (IDUs) aged 15-44 each year between 2005 and 2009 was estimated using capture-recapture methodology based on 4 data sources (2 treatment data bases: drug use and non-fatal overdose treatment; criminal justice (drug related offences) and mortality (injection drug use related deaths) data). Poisson log-linear regression models were applied to the matched data, with interactions between data sources fitted to replicate the dependencies between the data sources. Linear regression was used to estimate average change over time. RESULTS: There were 24305, 12,292, 238, 545 records and 8100, 1655, 155, 545 individual IDUs identified in the four capture sources (police, drug treatment, overdose, and death registry, accordingly) over the period 2005-2009. The estimated prevalence of IDUs among the population aged 15-44 declined from 2.7% (1.8-7.9%) in 2005 to 2.0% (1.4-5.0%) in 2008, and 0.9% (0.7-1.7%) in 2009. Regression analysis indicated an average reduction of about 1600 injectors per year. CONCLUSION: While the capture-recapture method has known limitations, the results are consistent with other data from Estonia. Identifying the drivers of change in the prevalence of injection drug use warrants further research.

Socio-demographic factors, health risks and harms associated with early initiation of injection among people who inject drugs in Tallinn, Estonia: evidence from cross-sectional surveys.

AIM: To explore socio-demographic factors, health risks and harms associated with early initiation of injecting (before age 16) among injecting drug users (IDUs) in Tallinn, Estonia. METHODS: IDUs were recruited using respondent driven sampling methods for two cross-sectional interviewer-administered surveys (in 2007 and 2009). Bivariate and multivariate logistic regression analysis was used to identify factors associated with early initiation versus later initiation. RESULTS: A total of 672 current IDUs reported the age when they started to inject drugs; the mean was 18 years, and about a quarter of the sample (n = 156) reported early initiation into injecting drugs. Factors significantly associated in multivariate analysis with early initiation were being female, having a lower educational level, being unemployed, shorter time between first drug use and injecting, high-risk injecting (sharing syringes and paraphernalia, injecting more than once a day), involvement in syringe exchange attendance and getting syringes from outreach workers, and two-fold higher risk of HIV seropositivity. CONCLUSIONS: Our results document significant adverse health consequences (including higher risk behaviour and HIV seropositivity) associated with early initiation into drug injecting and emphasize the need for comprehensive prevention programs and early intervention efforts targeting youth at risk. Our findings suggest that interventions designed to delay the age of starting drug use, including injecting drug use, can contribute to reducing risk behaviour and HIV prevalence among IDUs.

Multiple routes of drug administration and HIV risk among injecting drug users.

This study assesses relationships between drug administration routes and HIV serostatus, drug use, and sexual behaviors among current injecting drug users (IDUs) in Tallinn, Estonia. We recruited 350 IDUs for a cross-sectional risk behavior survey. Adjusted odds ratios (AORs) were calculated to explore injection risk behavior, sexual behavior, and HIV serostatus associated with multiple route use. Focus groups explored reasons why injectors might use non-injecting routes of administration. Those reporting multiple drug administration routes were less likely to be HIV seropositive (AOR = 0.49, 95% confidence interval [CI] = 0.25-0.97) and had almost twice the odds of having more than one sexual partner (AOR = 1.90, 95% CI = 1.01-3.60) and of reporting having sexually transmitted diseases (AOR = 2.38, 95% CI = 1.02-5.59). IDUs who engage in noninjecting drug use may be reducing their risk of acquiring HIV though sharing injection equipment, but if infected may be a critical group for sexual transmission of HIV to people who do not inject drugs.

Expanded syringe exchange programs and reduced HIV infection among new injection drug users in Tallinn, Estonia.

BACKGROUND: Estonia has experienced an HIV epidemic among intravenous drug users (IDUs) with the highest per capita HIV prevalence in Eastern Europe. We assessed the effects of expanded syringe exchange programs (SEP) in the capital city, Tallinn, which has an estimated 10,000 IDUs. METHODS: SEP implementation was monitored with data from the Estonian National Institute for Health Development. Respondent driven sampling (RDS) interview surveys with HIV testing were conducted in Tallinn in 2005, 2007 and 2009 (involving 350, 350 and 327 IDUs respectively). HIV incidence among new injectors (those injecting for < = 3 years) was estimated by assuming (1) new injectors were HIV seronegative when they began injecting, and (2) HIV infection occurred at the midpoint between first injection and time of interview. RESULTS: SEP increased from 230,000 syringes exchanged in 2005 to 440,000 in 2007 and 770,000 in 2009. In all three surveys, IDUs were predominantly male (80%), ethnic Russians (>80%), and young adults (mean ages 24 to 27 years). The proportion of new injectors decreased significantly over the years (from 21% in 2005 to 12% in 2009, p = 0.005). HIV prevalence among all respondents stabilized at slightly over 50% (54% in 2005, 55% in 2007, 51% in 2009), and decreased among new injectors (34% in 2005, 16% in 2009, p = 0.046). Estimated HIV incidence among new injectors decreased significantly from 18/100 person-years in 2005 and 21/100 person-years in 2007 to 9/100 person-years in 2009 (p = 0.026). CONCLUSIONS: In Estonia, a transitional country, a decrease in the HIV prevalence among new injectors and in the numbers of people initiating injection drug use coincided with implementation of large-scale SEPs. Further reductions in HIV transmission among IDUs are still required. Provision of 70 or more syringes per IDU per year may be needed before significant reductions in HIV incidence occur.

Evaluating recruitment among female sex workers and injecting drug users at risk for HIV using respondent-driven sampling in Estonia.

Few recent publications have highlighted theoretical and methodological challenges using respondent-driven sampling (RDS). To explore why recruitment with RDS may work in some populations and not in others, we assess the implementation of RDS to recruit female sex workers (FSWs) and injection drug users (IDUs) into a human immunodeficiency virus biological and risk behavior survey in Tallinn, Estonia. Recruitment of FSWs was slower and more challenging than that of IDUs. The IDU study recruited 350 participants within 7 weeks, while the FSW study recruited 227 participants over 28 weeks. Implementation modifications that did not negatively impact key RDS theoretical and methodological requirements were used to improve recruitment during the FSW study. We recommend that all RDS studies include a formative research process to involve the participation of target populations and key persons associated with these populations in the study planning and throughout the implementation processes to improve recruitment from the outset and to respond to poor recruitment during data collection.

CCL3L1 copy number is a strong genetic determinant of HIV seropositivity in Caucasian intravenous drug users.

BACKGROUND: A high copy number of CCL3L1, the most potent human immunodeficiency virus (HIV)-suppressive chemokine, associates with reduced HIV susceptibility. Whether CCL3L1 influences acquisition of multiple blood-borne infections (eg, hepatitis C virus [HCV], HIV, and hepatitis B virus [HBV] infections), which occur commonly among injection drug users (IDUs), is unknown. METHODS: We determined CCL3L1 copy number by real-time polymerase chain reaction among 374 Caucasian IDUs from Estonia; 285 were HCV positive, 208 were HIV positive, 177 were HCV and HIV positive, and 57 were HCV and HIV negative. RESULTS: In univariate and multivariate analyses, HCV and HBV seropositivity and duration of IDU each strongly predicted HIV seropositivity. A high CCL3L1 copy number (>2) was associated with an 80% reduced risk of acquiring HIV infection after adjusting for age, sex, HCV and HBV status, CCR5-Delta32 polymorphism, and IDU duration (odds ratio, 0.20; 95% confidence interval, 0.09-0.45). By contrast, CCL3L1 gene dose did not influence HCV seropositivity. Among HCV-positive IDUs, there was a 3.5-fold overrepresentation and 65% underrepresentation of a high CCL3L1 copy number among HCV-positive, HIV-negative subjects and HCV-positive, HIV-positive subjects, respectively. CONCLUSION: Among IDUs with extensive exposure to HCV and HIV, CCL3L1 copy number is a major determinant of HIV seropositivity but not of HCV seropositivity. The contrasting distribution of a protective high CCL3L1 copy number among HCV-positive, HIV-negative IDUs versus HCV-positive, HIV-positive IDUs may reflect that HIV preferentially selects for subjects with a low CCL3L1 gene dose.