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1.  A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs 
PLoS ONE  2016;11(6):e0156850.
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.
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.
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.
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.
PMCID: PMC4909289  PMID: 27304910
2.  Non-fatal overdoses and related risk factors among people who inject drugs in St. Petersburg, Russia and Kohtla-Järve, Estonia 
BMC Public Health  2015;15:1255.
This study seeks to identify the prevalence of, and risk factors associated with, non-fatal overdose among people currently injecting drugs (PWID) in St. Petersburg (Russia) and in Kohtla-Järve (Estonia).
Five hundred eighty-eight study participants in Kohtla-Järve (in 2012) and 811 in St. Petersburg (in 2012–2013) were recruited using respondent driven sampling for interviewing and HIV testing.
Three-quarters (76 %) of the current PWID were male. Participants from St. Petersburg were older (mean age 32.1 vs. 29.6 years, p < 0.0001) and reported a longer average duration of injecting drugs (mean duration: 13.3 vs. 10.9 years, p < 0.0001). Main drugs injected were opioids (fentanyl in Kohtla-Järve, heroin in St Petersburg). HIV prevalence was 63 % (95 % CI 59–67 %) in Kohtla-Järve and 56 % (95 % CI 52–59 %) in St. Petersburg. Two thirds of the PWID in Kohtla-Järve and St. Petersburg reported ever having experienced a drug overdose involving loss of consciousness or stopping breathing. In Kohtla-Järve, 28 % (95 % CI 24–31 %) of participants and, in St Petersburg, 16 % (95 % CI 14–19 %) of participants reported an overdose within the previous 12 months. Characteristics of injection drug use practice (longer duration of injection drug use, main drug injected), correlates of high-risk injection behaviour (higher injecting frequency, sharing), and problem alcohol use were associated with the risk of overdose within the previous 12 months. The significant factors effects did not differ between the sites.
PWID are at high risk for overdose. Effective overdose prevention efforts at the public health scale are therefore warranted.
PMCID: PMC4683801  PMID: 26684815
People who inject drugs; Overdose; Eastern Europe; Fentanyl; Opioids
3.  Association between HIV-1 tropism and CCR5 human haplotype E in a Caucasian population 
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.
We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping nine 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.
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 overrepresented among people with CCR5 human haplotype E (HHE) compared to those without this haplotype (13.0% vs 1.4%; p=0.006). People possessing CCR5 HHE had eleven times increased odds (OR=11.00; 95% CI 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral therapy (ARV), neither the presence of HHE nor the use of ARV were associated with X4 tropic viruses.
Our results suggest that CCR5 HHE as well as ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.
PMCID: PMC4146654  PMID: 24508837
CCR5; X4 tropic viruses; intravenous drug users
4.  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 
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.
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.
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.
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.
PMCID: PMC3566328  PMID: 23036651
Adolescents; injecting drug use; risk behaviour; Eastern Europe; Respondent Driven Sampling; HIV
5.  CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users 
PLoS ONE  2013;8(7):e70561.
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.
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.
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 (Padjusted = 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.
Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.
PMCID: PMC3723663  PMID: 23936229
6.  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%CI 0.25-0.97), 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 non-injecting 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.
PMCID: PMC3289756  PMID: 22116012
Injecting drug use; HIV; Risk behavior; Illicit drug use; Sexual risk behaviors
7.  Expanded syringe exchange programs and reduced HIV infection among new injection drug users in Tallinn, Estonia 
BMC Public Health  2011;11:517.
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.
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.
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).
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.
PMCID: PMC3146432  PMID: 21718469
8.  Enhanced tuberculosis case detection among substitution treatment patients: a randomized controlled trial 
BMC Research Notes  2011;4:192.
Historically, HIV, TB (tuberculosis) and illegal drug treatment services in Estonia have been developed as vertical structures. Related health care services are often provided by different health care institutions and in different locations. This may present obstacles for vulnerable groups, such as injecting drug users (IDU), to access the needed services. We conducted a small scale randomized controlled trial to evaluate a case management intervention aimed at increasing TB screening and treatment entry among IDUs referred from a methadone drug treatment program in Jõhvi, North-Eastern Estonia.
Of the 189 potential subjects, 112 (59%) participated. HIV prevalence was 86% (n = 96) and 7.4% (n = 8) of participants were interferon gamma release assay (IGRA) positive (6.5% were both HIV and IGRA-positive, n = 7). Overall, 44% of participants (n = 49) attended TB clinic, 17 (30%) from control group and 32 (57%) from case management group (p = 0.004). None of the participants were diagnosed with TB. In a multivariate model, those randomized to case management group were more likely to access TB screening services.
These findings demonstrate the urgent need for scaling up TB screening among IDUs and the value of more active approach in referring substitution treatment patients to TB services.
Trial registration NCT01290081
PMCID: PMC3138461  PMID: 21676222
9.  CCL3L1 copy number is a strong genetic determinant of HIV seropositivity in Caucasian intravenous drug users 
The Journal of infectious diseases  2010;201(5):730-739.
A high copy number of CCL3L1, the most potent HIV-suppressive chemokine, associates with reduced HIV susceptibility. Whether CCL3L1 influences acquisition of multiple blood-borne infections (HCV, HIV-1, HBV) that occurs commonly among intravenous drug users (IDUs) is unknown.
We determined CCL3L1 copy number by real-time PCR among 374 Caucasian IDUs from Estonia of whom 285 were HCV-positive, 208 HIV+, 177 HCV+/HIV+, and 57 HCV−/HIV−.
In univariate and multivariate analyses, HCV and HBV seropositivity, and duration of IDU each strongly predicted HIV seropositivity. A high CCL3L1 copy number (>2) associated with a 80% reduced risk of acquiring HIV, after adjusting for age, gender, HCV/HBV status, CCR5-Δ32 polymorphism and IDU duration (OR=0.20; 95% CI=0.09–0.45). By contrast, CCL3L1 gene dose did not influence HCV seropositivity. Among HCV+ IDUs, there was a 3.5-fold over- and 65% under-representation of a high CCL3L1 copy number among HCV+/HIV− and HCV+/HIV+ subjects, respectively.
Among IDUs exposed heavily to HCV/HIV, CCL3L1 copy number is a major determinant of HIV seropositivity, but not HCV seropositivity. The contrasting distribution of a protective high CCL3L1 copy number among HCV+/HIV− vs HCV+/HIV+ IDUs may reflect that HIV preferentially selects for subjects with a low CCL3L1 gene dose.
PMCID: PMC2836481  PMID: 20095832
chemokine copy number; HIV; HCV; IDU
10.  High-prevalence and high-estimated incidence of HIV infection among new injecting drug users in Estonia: need for large scale prevention programs 
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).
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.
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.
PMCID: PMC2925676  PMID: 18308743
Estonia; HIV; IDU; injection drug use; new injecting drug users
11.  Factors influencing quality of life of people living with HIV in Estonia: a cross-sectional survey 
Identification of factors that determine quality of life is important in order to better tailor health and social care services, and thereby improve the functioning and well being of people living with HIV. The estimated number of people living with HIV in eastern Europe and central Asia is 1.6 million. Little is known about the quality of life of people living with HIV in this region. The main purpose of the present study was to identify the factors influencing quality of life in a sample of HIV-infected persons in Estonia.
A convenient sample of 451 patients attending three infectious diseases clinics for routine HIV clinical care visits was recruited for a cross-sectional survey. The World Health Organization's Quality of Life HIV instrument was used to measure quality of life of the participants and medical data was abstracted from clinical records.
Good overall quality of life was reported by 42.6% (95% CI: 38.0–47.2%) of the study participants (53% men, 60% self-identify as injecting drug users, 82% <30 years of age, 30% with CD4+ T cell count <300 cells/mm3, and 22% on antiretroviral treatment). We identified the following variables as independent predictors of good overall quality of life: being currently employed or studying (AOR: 2.27, 95% CI: 1.18–4.38); and the absence of HIV-related symptoms (AOR: 2.31, 95% CI: 1.24–4.29).
A comprehensive and competent care system, including health care providers and social workers, is required for an effective response. In addition, social interventions should seek to enhance the economic and employment opportunities for people living with HIV in the region.
PMCID: PMC2717916  PMID: 19607721
12.  Comparison of injecting drug users who obtain syringes from pharmacies and syringe exchange programs in Tallinn, Estonia 
Both syringe exchange programs (SEPs) and pharmacy sales of syringes are available in Estonia, though the current high incidence and high prevalence of HIV among injection drug users (IDUs) in Tallinn, Estonia requires large-scale implementation of additional harm reduction programs as a matter of great urgency. The aims of this report were to compare risk behavior and HIV infection and to assess the prevention needs among IDUs who primarily use pharmacies as their source of sterile syringes with IDUs who primarily use SEPs in Tallinn.
A cross-sectional study using respondent-driven sampling was used to recruit 350 IDUs for an interviewer-administered survey and HIV testing. IDUs were categorized into two groups based on their self-reported main source for syringes within the last six months. Odds ratios with 95% CI were used to compare characteristics and risk factors between the groups.
The main sources of sterile needles for injection drug users were SEP/SEP outreach (59%) and pharmacies (41%). There were no differences in age, age at injection drug use initiation, the main drug used or experiencing overdoses. Those IDUs using pharmacies as a main source of sterile needles had lower odds for being infected with either HIV (AOR 0.54 95% CI 0.33–0.87) or HCV (AOR 0.10 95% CI 0.02–0.50), had close to twice the odds of reporting more than one sexual partner within the previous 12 months (AOR 1.88 95% CI 1.17–3.04) and engaging in casual sexual relationships (AOR 2.09 95% CI 1.24–3.53) in the last six months.
The data suggest that the pharmacy users were at a less "advanced" stage of their injection career and had lower HIV prevalence than SEP users. This suggests that pharmacies could be utilized as a site for providing additional HIV prevention messages, services for IDUs and in linking IDUs with existing harm reduction services.
PMCID: PMC2653475  PMID: 19232088

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