BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions.

Background: A "seek-test-treat" intervention (ARISTOTLE) was implemented in response to an outbreak of human immunodeficiency virus (HIV) infection among persons who inject drugs (PWID) in Athens. We assess trends in HIV incidence, prevalence, risk behaviors and access to prevention/treatment. Methods: Methods included behavioral data collection, provision of injection equipment, HIV testing, linkage to opioid substitution treatment (OST) programs and HIV care during 5 rounds of respondent-driven sampling (2012-2013). HIV incidence was estimated from observed seroconversions. Results: Estimated coverage of the target population was 88% (71%-100%; 7113 questionnaires/blood samples from 3320 PWID). The prevalence of HIV infection was 16.5%. The incidence per 100 person-years decreased from 7.8 (95% confidence interval, 4.6-13.1) (2012) to 1.7 (0.55-5.31) (2013; P for trend = .001). Risk factors for seroconversion were frequency of injection, homelessness, and history of imprisonment. Injection at least once daily declined from 45.2% to 18.8% (P < .001) and from 36.8% to 26.0% (P = .007) for sharing syringes, and the proportion of undiagnosed HIV infection declined from 84.3% to 15.0% (P < .001). Current OST increased from 12.2% to 27.7% (P < .001), and 48.4% of unlinked seropositive participants were linked to HIV care through 2013. Repeat participants reported higher rates of adequate syringe coverage, linkage to HIV care and OST. Conclusions: Multiple evidence-based interventions delivered through rapid recruitment in a large proportion of the population of PWID are likely to have helped mitigate this HIV outbreak.

Background: High numbers of human immunodeficiency virus type 1 (HIV-1) infections among people who inject drugs (PWID) have been diagnosed in Athens, Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection for migrants who inject drugs and to investigate whether transmissions occur more frequently among migrants than among Greek nationals. Methods: Multiple cross-sectional studies were pooled to assemble all persons diagnosed with HIV-1 in Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used maximum likelihood estimation. The hypothesis of ethnic compartmentalization was tested by reconstructing ancestral states of characters at the tips using the criterion of parsimony over a set of bootstrap trees. Results: Of 2274 persons, 38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID-specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non-Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the origin of their infection was assumed to be in Greece (postmigration). For PWID infected within LTNs, transmissions for subtype A and CRF14_BG occurred more frequently among migrants than would be expected by chance (phyloethnic study). Conclusions: Our analysis showed that the majority of infections among migrants occurred postmigration. The existence of significant transmission networking among migrants highlights that this population is a priority for HIV prevention. As molecular analysis can estimate the probable country of HIV infection, it can help to inform the design of public health strategies.

Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long-term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir/tenofovir (ETV/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10-center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/TDF for >/=1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5-10 (median, 6.8) years. HCCs have been diagnosed in 101/1,951 (5.2%) patients within the first 5 years and 17/1,205 (1.4%) patients within 5-10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness >/=12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender-Hepatitis B score at baseline or year 5 developed HCC. CONCLUSION: The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially >/=50 years), lower platelets, and liver stiffness >/=12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444-1453).

This analysis assessed the utility of the limiting antigen avidity assay (LAg). Samples of people who inject drugs (PWID) in Greece with documented duration of HIV-1 infection were tested by LAg. A LAg-normalized optical density (ODn) 1.5 corresponds to a recency window period of 130 days. The proportion true recent (PTR) and proportion false recent (PFR) were estimated in 28 seroconverters and in 366 samples collected >6 months after HIV diagnosis, respectively. The association between LAg ODn and HIV RNA level was evaluated in 232 persons. The PTR was 85.7%. The PFR was 20.8% but fell to 5.9% in samples from treatment-naive individuals with long-standing infection (>1 year), and to 0 in samples with the circulating recombinant form CRF35 AD. A LAg-based algorithm with a PFR of 3.3% estimated a similar incidence trend to that calculated by analyses based on HIV-1 seroconversions. In recently infected persons indicated by LAg, the median log10 HIV RNA level was high (5.30, interquartile range 4.56-5.90). LAg can help identify highly infectious HIV(+) individuals as it accurately identifies recent infections and is correlated with the HIV RNA level. It can also produce reliable estimates of HIV-1 incidence.

BACKGROUND AND AIM: The treatment of hepatitis C (HCV) with interferon (IFN)-free direct-acting antivirals (DAAs) is anticipated to change the future burden of disease. The aim of this study is to quantify the impact of IFN-free DAAs on HCV-related morbidity and mortality in Greece under different scenarios concerning treatment coverage and primary prevention, including the proposed by World Health Organization Global Hepatitis Strategy. METHODS: A previously described model was used to project the future disease burden up to 2030 under scenarios, which includes treatment based on the combination of pegylated-IFN with ribavirin (base case) and scenarios using DAAs therapies. RESULTS: Under the base case scenario, an increase in HCV-related morbidity and mortality is predicted in Greece (mortality in 2030: +23.6% compared with 2015). If DAAs are used with the same treatment coverage, the number of hepatocellular carcinoma cases and of liver related deaths are predicted to be lower by 4-7% compared with 2015. Under increased treatment coverage (from 2000 treated/year to approximately 5000/year in 2015-2020 and 2500/year subsequently), morbidity and mortality will decrease by 43-53% in 2030 compared with 2015. To achieve the WHO Global Hepatitis Strategy goals, a total number of 86 500 chronic hepatitis C patients will have to be treated during 2015-2030. CONCLUSIONS: Elimination of HCV in Greece by 2030 necessitates great improvements in primary prevention, implementation of large screening programs and high treatment coverage.

AIMS: To project the impact of scaling-up oral anti-viral therapy and harm reduction on chronic hepatitis C (CHC) prevalence and incidence among people who inject drugs (PWID) in Greece, to estimate the relationship between required treatment levels and expansion of harm reduction programmes to achieve specific targets and to examine whether hepatitis C virus (HCV) elimination among PWID is possible in this high-prevalence setting. DESIGN: A dynamic discrete time, stochastic individual-based model was developed to simulate HCV transmission among PWID incorporating the effect of HCV treatment and harm reduction strategies, and allowing for re-infection following treatment. SETTING/PARTICIPANTS: The population of 8300 PWID in Athens Metropolitan area. MEASUREMENTS: Reduction in HCV prevalence and incidence in 2030 compared with 2016. FINDINGS: Moderate expansion of HCV treatment (treating 4-8% of PWID/year), with a simultaneous increase of 2%/year in harm reduction coverage (from 44 to 72% coverage over 15 years), was projected to reduce CHC prevalence among PWID in Athens by 46.2-94.8% in 2030, compared with 2016. CHC prevalence would reduce to below 10% within the next 4-5 years if annual HCV treatment numbers were increased up to 16-20% PWID/year. The effect of harm reduction on incidence was more pronounced under lower treatment rates. CONCLUSIONS: Based on theoretical model projections, scaled-up hepatitis C virus treatment and harm reduction interventions could achieve major reductions in hepatitis C virus incidence and prevalence among people who inject drugs in Athens, Greece by 2030. Chronic hepatitis C could be eliminated in the next 4-5 years by increasing treatment to more than 16% of people who inject drugs per year combined with moderate increases in harm reduction coverage.

BACKGROUND: Despite great improvements in prevention over the last years, much has to be done to reduce new human immunodeficiency virus (HIV) infections. Substantial evidence shows that the six-month period of recent HIV infection contributes disproportionately to HIV transmission. OBJECTIVE: This study aims to investigate knowledge, normative beliefs, and attitudes of people who inject drugs (PWID) regarding recent HIV infection. METHODS: People who inject drugs in Athens, Greece were recruited in the fifth round of a respondent- driven sampling program (ARISTOTLE). The participants were tested for HIV and answered a structured questionnaire, which also included items on knowledge, normative beliefs, and attitudes regarding recent infection to address needs of the social network-based Transmission Reduction Intervention Project. The multivariable analyses included logistic regression models, which produced odds ratios (OR) and 95% confidence intervals (CI). RESULTS: In total, 1,407 people (mean age: 36.3 +/- 7.9 years old; males: 81.9%) took part in the fifth round of ARISTOTLE. Of these, 61.5% knew that HIV-infected people who are not on treatment are more likely to transmit HIV during the first six months of their infection and 58.4% reported that people in their network would react positively towards a recently HIV-infected person. People who inject drugs who were knowledgeable of recent HIV infection were more likely to disagree with statements such as that one should avoid all contact with a person recently infected by HIV (adjusted OR: 1.510, 95% CI: 1.090, 2.091) or more likely to agree with statements such as that an HIV+ person is much less likely to transmit HIV when h/she is on combination antiretroviral treatment (adjusted OR: 2.083, 95% CI: 1.231, 3.523). CONCLUSION: A considerable proportion of PWID in Athens, Greece, were aware of the high HIV transmission risk of recent HIV infection, although improvement is needed for some population segments. People who inject drugs who were knowledgeable of the role of recent HIV infection were more likely to have normative beliefs and attitudes that favor behaviors that could help rather than harm or stigmatize people who have recently been infected with HIV. Interventions that are based on the role of recent HIV infection in HIV transmission could be important to HIV prevention.