A rapid assessment of take-home naloxone provision during COVID-19 in Europe.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19 a global pandemic. In the following weeks, most European countries implemented national lockdowns to mitigate viral spread. Services for people who use drugs had to quickly revise their operating procedures to rearrange service provision while adhering to lockdown requirements. Given the scarcity of literature published on overdose prevention during COVID-19 in Europe, we aimed to examine how these changes to service provision affected take-home naloxone (THN) programmes and naloxone availability across Europe. METHODS: Between November 2020 and January 2021, we conducted a rapid assessment with country experts from European countries that provide THN. We sent country experts a template to report monthly THN distribution data (January 1, 2019-October 31, 2020) and a structured 6-item survey for completion. RESULTS: Responses were received from 14 of the 15 European countries with THN provision of which 11 participated in the rapid assessment: Austria, Denmark, England, Estonia, Lithuania, Northern Ireland, Norway, Scotland, Spain (Catalonia only), Sweden, and Wales. All reported reduced organisational capacity during COVID-19, and some put into place a range of novel approaches to manage the restrictions on face-to-face service provision. In six countries, the introduction of programme innovation occurred alongside the publication of government guidelines recommending increased THN provision during COVID-19. Eight of the eleven participating countries managed to maintain 2019-level monthly THN distribution rates or even increase provision during the pandemic. CONCLUSION: Through programme innovation supported by public guidelines, many European THN programmes managed to ensure stable or even increased THN provision during the pandemic, despite social distancing and stay-at-home orders affecting client mobility.

Take-Home Naloxone Kits: Attitudes and Likelihood-Of-Use Outcomes from a European Survey of Potential Overdose Witnesses.

BACKGROUND: Injectable naloxone is already provided as take-home naloxone (THN), and new concentrated intranasal naloxone is now being introduced in Europe. Despite evidence of the effectiveness and cost-effectiveness of THN, little is known about the attitudes of key target populations: people who use opioids (PWUO), family/friends, and staff. We examined the acceptability of different naloxone devices (ampoule, prefilled syringe, and concentrated nasal spray) across 5 European countries. OBJECTIVES: The aim of this study was to compare THN target groups (PWUO vs. family/friends vs. staff) in their past rates of witnessed overdose and THN administration (as indicators of future use), current THN device preference, and THN carriage on the day of survey. METHOD: Cross-sectional survey of respondents (age ≥18) in addiction treatment, harm reduction, and recovery services in Denmark, England, Estonia, Norway, and Scotland. A purpose-developed questionnaire (59 items) was administered in the local language electronically or in a pen-and-paper format. RESULTS: Among n = 725 participants, 458 were PWUO (63.2%), 214 staff (29.5%), and 53 (7.3%) family members. The groups differed significantly in their likelihood-of-future THN use (p < 0.001): PWUO had the highest rate of previously witnessing overdoses (352; 77.7%), and staff members reported the highest past naloxone use (62; 30.1%). Across all groups, most respondents (503; 72.4%) perceived the nasal spray device to be the easiest to use. Most reported willingness to use the spray in an overdose emergency (508; 73.5%), followed by the prefilled syringe (457; 66.2%) and ampoules (64; 38.2%). Average THN carriage was 18.6%, ranging from 17.4% (PWUO) to 29.6% (family members). CONCLUSION: Respondents considered the concentrated naloxone nasal spray the easiest device to use. Still, most expressed willingness to use the nasal spray as well as the prefilled syringe in an overdose emergency. Carriage rates were generally low, with fewer than 1 in 5 respondents carrying their THN kit on the day of the survey.

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.

A tale of two cities: stigma and health outcomes among people with HIV who inject drugs in St. Petersburg, Russia and Kohtla-Järve, Estonia.

Experiences of stigma are often associated with negative mental and physical health outcomes. The present work tested the associations between stigma and health-related outcomes among people with HIV who inject drugs in Kohtla-Järve, Estonia and St. Petersburg, Russia. These two cities share some of the highest rates of HIV outside of sub-Saharan Africa, largely driven by injection drug use, but Estonia has implemented harm reduction services more comprehensively. People who inject drugs were recruited using respondent-driven sampling; those who indicated being HIV-positive were included in the present sample (n = 381 in St. Petersburg; n = 288 in Kohtla-Järve). Participants reported their health information and completed measures of internalized HIV stigma, anticipated HIV stigma, internalized drug stigma, and anticipated drug stigma. Participants in both locations indicated similarly high levels of all four forms of stigma. However, stigma variables were more strongly associated with health outcomes in Russia than in Estonia. The St. Petersburg results were consistent with prior work linking stigma and health. Lower barriers to care in Kohtla-Järve may help explain why social stigma was not closely tied to negative health outcomes there. Implications for interventions and health policy are discussed.

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.

Condom use and partnership intimacy among drug injectors and their sexual partners in Estonia.

OBJECTIVES: Young age coupled with a high HIV prevalence among injection drug users (IDUs) and the prevalence of drug use in Eastern Europe can lead from an HIV epidemic concentrated among IDU to a self-sustained heterosexual HIV epidemic. Our objective was to explore the contexts of the prevention of sexual transmission of HIV among IDUs and their sexual partners and to provide insight into beliefs and behaviours related to condom use. METHODS: The authors undertook in-depth qualitative interviews to explore narratives about experience of preventing sexual transmission of HIV among 27 individuals (15 current IDUs and 12 main sexual partners of IDUs) in Kohtla-Järve, Estonia. RESULTS: The safe-sex 'norm' was not common and factors that tended to reduce condom use included valuing the relationship above health risks, established gender roles, perceptions that condoms distributed via harm reduction programmes were of low quality and the stigma attached to HIV status disclosure. HIV risk management strategies among participants included consistent condom use and serosorting but were countered by a fatalism that encompassed consciously subjecting oneself to the inevitability of HIV infection in an HIV-discordant sexual partnership. CONCLUSIONS: Qualitative methods can significantly contribute to the prevention of sexual transmission of HIV among and beyond IDUs by improving our understanding of risky behaviours and the reasons for such behaviours that can be incorporated into tailored public health interventions.

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.

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.

HIV infection and risk behaviour of primary fentanyl and amphetamine injectors in Tallinn, Estonia: implications for intervention.

BACKGROUND: Following a heroin shortage, fentanyl and 3-methylfentanyl, known as "China White" and "White Persian", have become the most widely used drugs, along with amphetamine, among injecting drug users (IDUs) in Tallinn, Estonia. METHODS: In order to assess the relationships between the injection of fentanyl and amphetamine, and levels of HIV prevalence and risk behaviour, 350 current IDUs were recruited using respondent-driven sampling for an interviewer-administered unlinked cross-sectional survey and HIV testing. IDUs were categorised into groups based on self-report of the main drug used within the last 28 days. RESULTS: 77% (256/331) of participants reported fentanyl and 23% (75/331) amphetamine as their main drug of injection. HIV prevalence was 27% (95% confidence interval [CI]: 18.45-35.51) and 62% (95% CI: 56.97-67.03) among amphetamine and fentanyl injectors, respectively. After adjustment, fentanyl injectors had three times the odds of being HIV positive (adjusted odds ratio [AOR]=2.89; 95% CI: 1.55-5.39). They also had higher odds for injecting in the street with a previously used needle/syringe (AOR=2.39; 95% CI: 1.14-5.04) and sharing a needle/syringe with somebody known to have HIV (AOR=3.00, 95% CI: 1.33-6.79). Fentanyl injectors also had higher odds for lifetime overdose (AOR=3.02, 95% CI: 1.65-5.54). CONCLUSION: The injection of fentanyl is associated with elevated injecting risk behaviour derived from injection practice and situational risk factors, and needs urgently targeted interventions.

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.

Comparison of injecting drug users who obtain syringes from pharmacies and syringe exchange programs in Tallinn, Estonia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.