Incidence of primary hepatitis C infection among people who inject drugs during 2012-2020 in Athens, Greece.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.

Comparison of Integrase Strand Transfer Inhibitors (INSTIs) and Protease-Boosted Inhibitors (PIs) on the Reduction in Chronic Immune Activation in a Virally Suppressed, Mainly Male Population Living with HIV (PLWH).

Background and Objectives: The success of combined antiretroviral therapy (cART) has led to a dramatic improvement in the life expectancy of people living with HIV (PLWH). However, there has been an observed increase in cardiometabolic, bone, renal, hepatic, and neurocognitive manifestations, as well as neoplasms, known as serious non-AIDS events/SNAEs, compared to the general population of corresponding age. This increase is linked to a harmful phenomenon called inflammaging/immunosenescence, which is driven by chronic immune activation and intestinal bacterial translocation. In this study, we examined immunological and metabolic parameters in individuals receiving current cART. Materials and Methods: The study was conducted at Laiko General Hospital in Athens, Greece. Plasma concentrations of sCD14, IL-6, SuPAR, I-FABP, and LBP were measured in virally suppressed PLWH under cART with at least 350 CD4 lymphocytes/µL. We compared these levels between PLWH receiving integrase strand transfer inhibitors (INSTIs) and protease inhibitors (PIs) and attempted to correlate them with chronic immune activation and metabolic parameters. Results: Data from 28 PLWH were analyzed, with a mean age of 52 and 93% being males. Among the two comparison groups, IL-6 levels were higher in the PIs group (5.65 vs. 7.11 pg/mL, p = 0.03). No statistically significant differences were found in the other measured parameters. A greater proportion of PLWH under INSTIs had normal-range LBP (33% vs. 0%, p = 0.04). When using inverse probability of treatment weighting, no statistically significant differences in the measured parameters were found between the two groups (sCD14 p = 0.511, IL-6 p = 0.383, SuPAR p = 0.793, I-FABP p = 0.868, and LBP p = 0.663). Glucose levels were found to increase after viral suppression in the entire sample (92 mg/dL vs. 98 mg/dL, p = 0.009). Total (191 mg/dL vs. 222 mg/dL, p = 0.005) and LDL cholesterol (104 mg/dL vs. 140 mg/dL, p = 0.002) levels were higher in the PIs group. No significant differences were observed in liver and renal function tests. Conclusions: Further investigation is warranted for PLWH on cART-containing INSTI regimens to explore potential reductions in chronic immune activation and intestinal bacterial translocation.

Mapping frailty in people living with HIV: A nationwide study in Greece.

OBJECTIVES: Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data. METHODS: Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored. RESULTS: The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/µl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty. CONCLUSIONS: Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.

EAES, SAGES, and ESCP rapid guideline: bowel preparation for minimally invasive colorectal resection.

BACKGROUND: Variation exists in practice pertaining to bowel preparation before minimally invasive colorectal surgery. A survey of EAES members prioritized this topic to be addressed by a clinical practice guideline. OBJECTIVE: The aim of the study was to develop evidence-informed clinical practice recommendations on the use of bowel preparation before minimally invasive colorectal surgery, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: This is a collaborative project of EAES, SAGES, and ESCP. We updated a previous systematic review and performed a network meta-analysis of interventions. We appraised the certainty of the evidence for each comparison, using the GRADE and CINeMA methods. A panel of general and colorectal surgeons, infectious diseases specialists, an anesthetist, and a patient representative discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost, and use of resources, moderated by a GIN-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests either oral antibiotics alone prior to minimally invasive right colon resection or mechanical bowel preparation (MBP) plus oral antibiotics; MBP plus oral antibiotics prior to minimally invasive left colon and sigmoid resection, and prior to minimally invasive right colon resection when there is an intention to perform intracorporeal anastomosis; and MBP plus oral antibiotics plus enema prior to minimally invasive rectal surgery (conditional recommendations); and recommends MBP plus oral antibiotics prior to minimally invasive colorectal surgery, when there is an intention to localize the lesion intraoperatively (strong recommendation). The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/LwvKej . CONCLUSION: This guideline provides recommendations on bowel preparation prior to minimally invasive colorectal surgery for different procedures, using highest methodological standards, through a structured framework informed by key stakeholders. Guideline registration number PREPARE-2023CN045.

Predictive score for patients with carbapenemase-producing enterobacterales colonization upon admission in a tertiary care hospital in an endemic area.

OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) comprise important nosocomial pathogens worldwide. Colonized patients are the source of further dissemination in healthcare settings. Considering that timely detection of CPE carriers is pivotal but universal screening is unfeasible, we aimed to develop and validate a prediction score to detect patients harbouring CPE on hospital admission. METHODS: The study was conducted in a tertiary care hospital located in a CPE endemic area. Rectal swabs were obtained from 2303 patients, screened shortly after hospital admission. The Enterobacterales isolated in cultures were examined for the presence of blaVIM, KPC, NDM, OXA-48 by PCR. Demographic data and patient history of the previous 6 months were recorded. Risk factors for CPE carriage were identified using a multivariable logistic regression model and a points-system risk score was developed. The discriminative ability of the risk score was assessed using the AUC and its predictive performance was validated in a second dataset of 1391 patients in a different time period. RESULTS: Seven predictors were identified: previous CPE colonization or infection, prior hospitalization, stay in a long-term health care facility, history of ≥2 interventions, renal replacement therapy, diabetes with end-organ damage and Karnofsky score. The developed risk score in the derivation dataset ranged between 0 and 79 points, with an AUC of 0.84 in the derivation and 0.85 in the validation dataset. CONCLUSIONS: This prediction tool may assist in identifying patients who are at risk of harbouring CPE on hospital admission in an endemic area and guide clinicians to implement prompt and appropriate infection control measures.

Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors.

OBJECTIVES: HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis. METHODS: Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B. RESULTS: Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks. CONCLUSIONS: We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.

Tracking missed opportunities for an early HIV diagnosis in a population of people living with HIV with known time of infection.

PURPOSE: The goal of 90-90-90 first requires the expansion of access to HIV testing. Our aim was to record frequencies of HIV indicator conditions (ICs) and identify missed opportunities for an early HIV diagnosis. METHODS: We retrospectively identified ICs in a population of 231 people living with HIV with known infection dates who attended our clinic. The study population was divided into four groups: (1) those self-tested pre-emptively (47/231, 20.3%), (2) those offered targeted testing based on risk factors (67/231, 29%), (3) those tested after an IC (73/231, 31.6%) and (4) those who were not offered testing after an IC (44/231, 19%). HIV acquisition dates were estimated by molecular clock analysis. RESULTS: A total of 169 healthcare contacts (HCCs) were recorded. The most frequent HCC was mononucleosis-like syndrome (20.1%), unexplained weight loss (10.7%) and STIs (10.1%). AIDS-defining conditions were detected in 11.8%. Only 62.4% (73/117) of those with an IC were offered testing after their first HCC. Patients in group 4 had statistically significant delay in diagnosis compared with group 3 (109.1 weeks (IQR 56.4-238.6) vs 71.6 weeks (IQR 32.3-124.6)). The proportion of patients diagnosed as late presenters in each group was: (1) 16/47 (34%), (2) 37/67 (55.2%), (3) 43/73 (58.9%) and (4) 27/44 (61.4%) (p=0.027). CONCLUSIONS: Our study uses a combination of molecular and clinical data and shows evidence that late presentation occurs in a high proportion of patients even in the presence of an IC. Given that risk-based targeted testing has low coverage, IC-guided testing provides a reasonable alternative to facilitate earlier HIV diagnosis and to improve late diagnosis across Europe and globally.

Immunogenicity of a third dose of the BNT162b2 COVID-19 vaccine in patients with CLL: effects on treatment selection.

Patients with chronic lymphocytic leukemia (CLL) show suboptimal responses to the vaccines against SARS-CoV-2; it has been shown though that a booster dose of the BNT162b2 vaccine may lead to a significant increase in the seroconversion rates of immunocompromised patients. We conducted a prospective, non-interventional study to evaluate the immunogenicity of a third dose of the BNT162b2 vaccine in adult patients with CLL. Sera were tested before the first, after the second, and before and after the third dose for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD). Thirty-nine patients with CLL were included in the study. The seroconversion rate increased from 28.2% before the third dose to 64.1% after the third dose and was higher in treatment-naïve patients (72.7% versus 47.1% in actively treated patients, p = 0.042). All but one patient achieving a seroconversion after the second dose retained after the third, while eight patients not achieving a seroconversion after the second dose (38.1%), did so after the third. Moreover, patients actively treated with venetoclax had a higher seroconversion rate than those treated with ibrutinib (87.5% versus 14.3%, p = 0.001). This study confirms the beneficial effect of a third dose of the BNT162b2 vaccine on the seroconversion rate in patients with CLL. Our results also strongly suggest that the use of venetoclax is correlated with higher immunogenicity/seroconversion rates than that of ibrutinib, a finding that has been reported by another study. A treatment strategy change during the pandemic favoring the use of venetoclax may be suggested based on our results, although these results should be validated in larger studies.

Pre-exposure Prophylaxis Persistence Among Greek Sexual Minority Men: Results from PrEP for Greece (P4G) Study.

Nearly half the new HIV infections in Greece occur in sexual minority men, yet pre-exposure prophylaxis is not currently supported in the national HIV program. We examined factors associated with PrEP persistence among Greek SMM in PrEP for Greece, the first PrEP study in Greece. Participants (n = 100) were recruited from 2016 to 2018 through respondent-driven sampling among SMM in Athens, receiving supplies for daily PrEP at interval visits over 12-months. PrEP persistence, operationalized as Total PrEP Time, was high, 74% of participants achieving perfect persistence. Higher alcohol risk scores (OR 1.27, 95% CI 1.08-1.49) and adherence to HIV testing guidelines (OR 1.23, 95% CI 1.00-1.51) were associated with persistence. Housing impermanence (OR 0.14, 95% CI 0.04-0.48) and serostatus disclosure concerns (OR 0.77, 95% CI 0.60-0.97) were associated with limited PrEP persistence. While PrEP persistence among Greek SMM is high, socioeconomic factors and societal attitudes may challenge prevention efforts.

A Network Approach to Determine Optimization of PrEP Uptake in Athens, Greece.

Although the HIV epidemic in Athens, Greece has reemerged and spread in men who have sex with men (MSM), state-supported PrEP programs have not been instituted. A PrEP intervention was implemented building upon an existing network cohort of MSM (308 participants; 1212 network members). A PrEP intervention cohort of 106 participants was selected based upon sex behaviors. Individual, partner, and network characteristics were compared between the cohorts. The PrEP cohort members were more highly connected and in more influential positions in the network than their peers. Further, their sexual network connections' behaviors increased their vulnerability to HIV infection relative to the rest of the network's sex partners. This included greater stimulant use (24.2% vs 7.0%; χ2 = 28.2; p < 0.001), greater rates of at least weekly condomless sex (OR = 2.7; 95% CI 2.1-3.5; χ2 = 59.2; p < 0.001) and at least weekly use of drugs or alcohol during sex (OR = 3.4; 95% CI 2.6-4.3; χ2 = 89.7; p < 0.001). Finally the PrEP cohort's social networks showed similarly increased vulnerability to seroconversion, including greater rates of injection drug use (4.1% vs 0.5%; χ2 = 3.9; p = 0.04), greater stimulant use (33.6% vs 14.6%; χ2 = 16.9, p < 0.001), and higher rates of recent STIs (21.6% vs 13.1%; χ2 = 4.4; p = 0.04). Thus, this PrEP intervention engaged individuals in vulnerable positions with vulnerable connections within an MSM community.

Skin manifestations of Pseudomonas aeruginosa infections.

PURPOSE OF REVIEW: Pseudomonas aeruginosa is an opportunistic pathogen with considerable morbidity and mortality, particularly in vulnerable hosts. Skin manifestations are common, either representing local inoculation or secondary skin seeding following bloodstream infections. As patients with various predisposing conditions are expanding, we sought to review the most recent published evidence regarding epidemiology, risk factors and diagnosis of skin manifestations of P. aeruginosa. RECENT FINDINGS: New data exist on epidemiology and diagnosis of skin infections; systemic infections are impacted by multidrug-resistance issues and host immune status. SUMMARY: Green nail syndrome, toe web infection, hot tub folliculitis, hot hand-foot infection and external otitis are the most common infections originating from the skin per se. Local treatments are the cornerstone and prognosis is favorable in immunocompetent hosts. Ecthyma gangrenosum and P. aeruginosa subcutaneous nodules are usually associated with bloodstream infections and occur primarily in immunocompromised hosts. Necrotizing skin and soft tissue infections occur in diabetic, alcoholic and immunocompromised patients; management requires a multidisciplinary team with surgical approach. Burn wound infections may also be challenging, requiring a specialized team. In all the four latter types of P. aeruginosa skin infections portending significant morbidity and mortality, systemic antibiotics are an integral part of the treatment.

Cardiac adiposity as a modulator of cardiovascular disease in HIV.

BACKGROUND: With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation. AIMS: This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era. MATERIALS & METHODS: Review of contemporary literature on this topic. DISCUSSION: Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH. CONCLUSIONS: High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.

Earlier treatment initiation is associated with a decreased number of HIV-1 subtype A1 transmissions in Greece.

OBJECTIVES: Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. METHODS: Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. RESULTS: A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. CONCLUSIONS: Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV.

Cardiovascular disease (CVD) has emerged as a leading cause of non-HIV-related mortality among people living with HIV (PLWH). Despite the growing CVD burden in PLWH, there is concern that general population risk score models may underestimate CVD risk in these patients. Imaging modalities have received mounting attention lately to better understand the pathophysiology of subclinical CVD and provide improved risk assessment in this population. To date, traditional and well-established techniques such as echocardiography, pulse wave velocity, and carotid intima thickness continue to be the basis for the diagnosis and subsequent monitoring of vascular atherosclerosis and heart failure. Furthermore, novel imaging tools such as cardiac computed tomography (CT) and cardiac CT angiography (CCTA), positron emission tomography/CT (PET/CT), and cardiac magnetic resonance (CMR) have provided new insights into accelerated cardiovascular abnormalities in PLWH and are currently evaluated with regards to their potential to improve risk stratification.

Bloodstream infections by gram-negative bacteria in kidney transplant patients: Incidence, risk factors, and outcome.

BACKGROUND: Kidney transplant recipients (KTRs) are at increased risk of infections. METHODS: The aims of this study were to describe the incidence of bloodstream infections (BSIs) by gram-negative bacteria in a cohort of KTRs, the risk factors for BSI due to multi-drug-resistant (MDR) gram-negative bacteria, and the predictors for unfavorable outcome, defined as death or nephrectomy or return to dialysis, within 30 days from BSI. We conducted a retrospective cohort study at the renal transplant unit of a tertiary care hospital in Athens, Greece. RESULTS: In a total of 1962 KTRs, we recorded 195 BSI episodes in 182 single patients (male/female = 97/85), with a median (interquartile range) age of 57.2 (44-64.9) years. The incidence was 1.393/100 patient-years. The most common source of infection was urinary tract (70.9%), and Escherichia coli (63.7%) was the most common pathogen. 19.2% of the infecting organisms were MDR; previous antibiotic use (OR 8.2; CI 2.1-32.9) and previous stay in the intensive care unit (OR 34.2; CI 1.6-730.2) were associated with MDR BSIs. 6% of patients died, and 2.2% underwent nephrectomy, while no patients had to return to dialysis. Diabetes mellitus (OR 8.1; 95% CI 1.3-50.3), Pseudomonas aeruginosa BSI (OR 46.1; 95% CI 3.9-552.3), and septic shock (OR 46.7; 95% CI 1.7-1304.9) were independent predictors of unfavorable outcome. CONCLUSION: Bloodstream infections in KTRs have a significant impact on allograft and patients outcome.

Identifying, linking, and treating people who inject drugs and were recently infected with HIV in the context of a network-based intervention.

Identifying and linking people to care soon after HIV infection could limit viral transmission and protect their health. This work aims at describing the continuum of care among recently HIV-infected people who inject drugs (PWID) and participated in an intervention in the context of an HIV outbreak in Athens, Greece. The Transmission Reduction Intervention Project (TRIP) conducted risk network-based contact tracing and screened people for recent HIV infection. A comprehensive approach with a case management component that aimed to remove barriers to accessing care was adopted. Follow-up data on antiretroviral treatment (ART) and HIV-RNA levels were obtained from HIV clinics. TRIP enrolled 45 recently HIV-infected PWID (80% male) with a median viral load at recruitment of 5.43 log10 copies/mL. Of the recently infected persons in TRIP, 87% were linked to care; of these, 77% started ART; and of those on ART, 89% achieved viral load <200 copies/mL. TRIP and its public health allies managed to get most of the recently HIV-infected PWID who were identified by the program into care and many of them onto ART. This resulted in very low HIV-RNA levels. Treatment as prevention can work if individuals are aided in overcoming difficulties in entry to, or attrition from care.

Molecular Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals in a Network-Based Intervention (Transmission Reduction Intervention Project): Phylogenetics Identify HIV-1-Infected Individuals With Social Links.

Background: The Transmission Reduction Intervention Project (TRIP) is a network-based intervention that aims at decreasing human immunodeficiency virus type 1 (HIV-1) spread. We herein explore associations between transmission links as estimated by phylogenetic analyses, and social network-based ties among persons who inject drugs (PWID) recruited in TRIP. Methods: Phylogenetic trees were inferred from HIV-1 sequences of TRIP participants. Highly supported phylogenetic clusters (transmission clusters) were those fulfilling 3 different phylogenetic confidence criteria. Social network-based ties (injecting or sexual partners, same venue engagement) were determined based on personal interviews, recruitment links, and field observation. Results: TRIP recruited 356 individuals (90.2% PWID) including HIV-negative controls; recently HIV-infected seeds; long-term HIV-infected seeds; and their social network members. Of the 150 HIV-infected participants, 118 (78.7%) were phylogenetically analyzed. Phylogenetic analyses suggested the existence of 13 transmission clusters with 32 sequences. Seven of these clusters included 14 individuals (14/32 [43.8%]) who also had social ties with at least 1 member of their cluster. This proportion was significantly higher than what was expected by chance. Conclusions: Molecular methods can identify HIV-infected people socially linked with another person in about half of the phylogenetic clusters. This could help public health efforts to locate individuals in networks with high transmission rates.

Rapid Decline in HIV Incidence Among Persons Who Inject Drugs During a Fast-Track Combination Prevention Program After an HIV Outbreak in Athens.

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.

Molecular Tracing of the Geographical Origin of Human Immunodeficiency Virus Type 1 Infection and Patterns of Epidemic Spread Among Migrants Who Inject Drugs in Athens.

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.

HBV-DNA levels predict overall mortality in HIV/HBV coinfected individuals.

The coinfection of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has been associated with increased death rates. However, the relevant research has mostly relied on serologic HBV testing [HBV surface antigen (HBsAg)]. The aim of this work was to explore the relationship of HBV viraemia with overall mortality among HIV/HBV coinfected individuals. The analysis included 1,609 HIV seropositives of a previously described cohort (1984-2003) with limited exposure to tenofovir (12%) and a median follow-up of approximately 5 years. Those with persistent expression of HBsAg were further tested for HBV-DNA. The data were analyzed using Poisson regression models. Totally, 101 participants were chronic carriers of HBsAg (6.28%). Of these, 81 were tested for HBV-DNA. The median HBV-DNA levels were 3.81 log (base-10) International Units (IU)/ml. A third (31%) of those tested for HBV-DNA had received tenofovir. Before developing acquired immune deficiency syndrome (AIDS), the adjusted incidence rate ratio (IRR) for all-cause mortality of coinfected patients with HBV viraemia above the median value versus the HIV monoinfected group was 3.44 [95% confidence interval (CI): 1.05-11.27]. Multivariable regressions in the coinfected group only (n = 81) showed that one log-10 increase in HBV-DNA levels was associated with an elevated risk for death (IRR: 1.24, 95%CI: 1.03-1.49). HBV-DNA levels predict overall mortality in the setting of HIV/HBV coinfection, especially during the period before developing AIDS, and could thus help prioritize needs and determine the frequency of medical monitoring.