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Background and Aims: The human immunodeficiency virus (HIV) outbreak among people who inject drugs (PWID) in Athens, Greece in 2011–13 was the largest recent epidemic in Europe and North America. We aimed to assess trends in HIV prevalence, drug use and access to prevention among PWID in Athens to estimate HIV incidence and identify risk factors and to explore HIV‐1 dispersal using molecular methods during 2014–20. Methods: Two community‐based HIV/hepatitis C programmes on PWID were implemented in 2012–13 (n = 3320) and 2018–20 (n = 1635) through consecutive respondent‐driven sampling (RDS) rounds. PWID were uniquely identified among rounds/programmes. We obtained RDS‐weighted HIV prevalence estimates per round for 2018–20 and compared them to 2012–13. We assessed changes in HIV status, behaviours and access to prevention in PWID participating in both periods. We estimated HIV incidence in a cohort of seronegative PWID as the number of HIV seroconversions/100 person‐years during 2014–20 and used Cox regression to identify associated risk factors. Molecular sequencing and phylogenetic analysis were performed in HIV seroconverters. Results: HIV prevalence per round ranged between 12.0 and 16.2% in 2012–13 and 10.7 and 11.3% in 2018–20 with overlapping 95% confidence intervals (95% CI). Among PWID participating in both programmes, HIV prevalence (95% CI) increased from 14.2% (11.7–17.1%) in 2012–13 to 22.0% (19.0–25.3%) in 2018–20 (P < 0.001). There was a deterioration in socio‐economic characteristics such as homelessness [from 16.2% (95% CI = 13.5–19.2%) to 25.6% (22.3–29.0%)], a shift in cocaine use [16.6% (13.9–19.6%) versus 28.1% (24.7–31.7%], reduced access to free syringes [51.8% (48.0–55.7%) versus 44.5% (40.7–48.3%)] and a decrease in daily injecting [36.2% (32.6–39.9%) versus 28.5% (25.2–32.1%)]. HIV incidence (95% CI) in 2014–20 was 1.94 (1.50–2.52) new cases/100 person‐years and younger age, lower educational level, larger injection network and daily injecting were risk factors. Almost 9% of HIV seroconversions occurred within a newly expanding phylogenetic cluster. Conclusions: In Athens, Greece, compared with the period 2012–13, in the period 2018–20 there was a deterioration in socio‐economic conditions among people who inject drugs, an increase in the use of cocaine, reduced access to needle and syringe programmes and stable low levels of human immunodeficiency virus testing. Ongoing human immunodeficiency virus transmission was documented during 2014–20 in existing as well as new transmission clusters. [ABSTRACT FROM AUTHOR]

Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018–2022. PWID recruited from two community-based programs in Athens and Thessaloniki during 2018–2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model. Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15–3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68–3.58) in Athens and 4.48 per 100 PYs (3.74–5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018–2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17–17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death. Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018–2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed. [ABSTRACT FROM AUTHOR]