Is use of opioid agonist treatment associated with broader primary healthcare use among men with recent injecting drug use histories following release from prison? A prospective cohort study.

BACKGROUND: A precipitous decline in health status among people recently released from prison is common. In Victoria, Australia, opioid agonist treatment (OAT) in the community involves frequent contact with primary care, potentially facilitating broader use of primary healthcare services. Among a cohort of men who injected drugs regularly pre-imprisonment, we estimated differences in rates of primary healthcare use and medication dispensation between people who did and did not receive OAT post-release. METHODS: Data came from the Prison and Transition Health Cohort Study. Three-month post-release follow-up interviews were linked with primary care and medication dispensation records. Generalised linear models were fit with one exposure (OAT: none/partial/complete) for 13 outcomes relating to primary healthcare use, pathology testing, and medication dispensation, adjusted for other covariates. Coefficients were reported as adjusted incidence rate ratios (AIRR). RESULTS: Analyses included 255 participants. Compared to no OAT use, both partial and complete OAT use were associated with increased rates of standard (AIRR: 3.02, 95%CI: 1.88-4.86; AIRR: 3.66, 95%CI: 2.57-5.23), extended (AIRR: 2.56, 95%CI: 1.41-4.67; AIRR: 2.55, 95%CI: 1.60-4.07) and mental health-related (AIRR: 2.71, 95%CI: 1.42-5.20; AIRR: 2.27, 95%CI: 1.33-3.87) general practitioner (GP) consultations, total medication (AIRR: 1.88, 95%CI: 1.19-2.98; AIRR: 2.40, 95%CI: 1.71-3.37), benzodiazepine (AIRR: 4.99, 95%CI: 2.81-8.85; AIRR: 8.30, 95%CI: 5.28-13.04) and gabapentinoid (AIRR: 6.78, 95%CI: 3.34-13.77; AIRR: 4.34, 95%CI: 2.37-7.94) dispensations, respectively. Partial OAT use was also associated with increased after-hours GP consultations (AIRR: 4.61, 95%CI: 2.24-9.48) and complete OAT use? with increased pathology utilisation (e.g. haematological, chemical, microbiological or immunological tissue/sample testing; AIRR: 2.30, 95%CI: 1.52-3.48). CONCLUSION: We observed higher rates of primary healthcare use and medication dispensation among people who reported partial and complete OAT use post-release. Findings suggest that access to OAT post-release may have a collateral benefit in supporting broader health service utilisation, underscoring the importance of retention in OAT after release from prison.

Prospective study of retention in opioid agonist treatment and contact with emergency healthcare following release from prisons in Victoria, Australia.

BACKGROUND: People recently released from prison engage with emergency healthcare at greater rates than the general population. While retention in opioid agonist treatment (OAT) is associated with substantial reductions in the risk of opioid-related mortality postrelease, it is unknown how OAT affects contact with emergency healthcare. In a cohort of men who injected drugs regularly prior to imprisonment, we described rates of contact with ambulance services and EDs, and their associations with use of OAT, in the 3 months after release from prison. METHODS: Self-report data from a prospective observational cohort of men who regularly injected drugs before a period of sentenced imprisonment, recruited between September 2014 and May 2016, were linked to state-wide ambulance and ED records over a 3-month postrelease period in Victoria, Australia. We used generalised linear models to estimate associations between OAT use (none/interrupted/retained) and contact with ambulance and EDs postrelease, adjusted for other covariates. RESULTS: Among 265 participants, we observed 77 ambulance contacts and 123 ED contacts over a median of 98 days of observation (IQR 87-125 days). Participants who were retained in OAT between prison release and scheduled 3-month postrelease follow-up interviews had lower rates of contact with ambulance (adjusted incidence rate ratio (AIRR) 0.33, 95% CI 0.14 to 0.76) and ED (AIRR 0.43, 95% CI 0.22 to 0.83), compared with participants with no OAT use postrelease. Participants with interrupted OAT use did not differ from those with no OAT use in rates of contact with ambulance or ED. CONCLUSION: We found lower rates of contact with emergency healthcare after release among people retained in OAT, but not among people reporting interrupted OAT use, underscoring the benefits of postrelease OAT retention. Strategies to improve accessibility and support OAT retention after leaving prison are important for men who inject drugs.

Psychiatric well-being among men leaving prison reporting a history of injecting drug use: A longitudinal analysis.

BACKGROUND: Community reintegration from prison is typically stressful, with several health and social outcomes impacting psychiatric well-being during this time, often exacerbated among individuals with histories of drug use. Longitudinal data was used to assess change in psychiatric well-being over 2 years following release from prison among men who reported a recent history of injecting drug use. METHODS: Data for this study come from the Prison and Transition Health cohort study of 400 men recruited in prison prior to release and followed up over three time points. Psychiatric well-being was assessed using the 12-item General Health Questionnaire. We calculated change in individual General Health Questionnaire scores between interviews and identified covariates associated with General Health Questionnaire score using linear mixed-effects regression. RESULTS: Data from 690 follow-up interviews among 326 participants were included in analyses. There was considerable variation in individuals' General Health Questionnaire scores. Moving accommodation frequently and frequent illicit drug injections were associated with an increase in General Health Questionnaire score (i.e. decline in psychiatric well-being). Two or more prior adult imprisonment episodes, social supports and past month primary healthcare attendance were associated with a decrease in General Health Questionnaire score. CONCLUSION: Our findings identify health, social and structural influences on psychiatric well-being after release from prison that can inform re-entry programmes to support community reintegration.

Strategies to maximise study retention and limit attrition bias in a prospective cohort study of men reporting a history of injecting drug use released from prison: the prison and transition health study.

BACKGROUND: There are significant challenges associated with studies of people released from custodial settings, including loss to follow-up in the community. Interpretation of findings with consideration of differences between those followed up and those not followed up is critical in the development of evidence-informed policies and practices. We describe attrition bias in the Prison and Transition Health (PATH) prospective cohort study, and strategies employed to minimise attrition. METHODS: PATH involves 400 men with a history of injecting drug use recruited from three prisons in Victoria, Australia. Four interviews were conducted: one pre-release ('baseline') and three interviews at approximately 3, 12, and 24 months post-release ('follow-up'). We assessed differences in baseline characteristics between those retained and not retained in the study, reporting mean differences and 95% confidence intervals (95% CIs).  RESULTS: Most participants (85%) completed at least one follow-up interview and 162 (42%) completed all three follow-up interviews. Retained participants were younger than those lost to follow-up (mean diff - 3.1 years, 95% CI -5.3, - 0.9). There were no other statistically significant differences observed in baseline characteristics. CONCLUSION: The high proportion of participants retained in the PATH cohort study via comprehensive follow-up procedures, coupled with extensive record linkage to a range of administrative datasets, is a considerable strength of the study. Our findings highlight how strategic and comprehensive follow-up procedures, frequent contact with participants and secondary contacts, and established working relationships with the relevant government departments can improve study retention and potentially minimise attrition bias.

Estimating the number of new hepatitis C infections in Australia in 2015, prior to the scale-up of direct-acting antiviral treatment.

BACKGROUND AND AIM: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years. METHODS: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015. RESULTS: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015. CONCLUSIONS: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies.

S-Trap Eliminates Cell Culture Media Polymeric Surfactants for Effective Proteomic Analysis of Mammalian Cell Bioreactor Supernatants.

Proteomic analysis of bioreactor supernatants can inform on cellular metabolic status, viability, and productivity, as well as product quality, which can in turn help optimize bioreactor operation. Incubating mammalian cells in bioreactors requires the addition of polymeric surfactants such as Pluronic F68, which reduce the sheer stress caused by agitation. However, these surfactants are incompatible with mass spectrometry proteomics and must be eliminated during sample preparation. Here, we compared four different sample preparation methods to eliminate polymeric surfactants from filtered bioreactor supernatant samples: organic solvent precipitation; filter-assisted sample preparation (FASP); S-Trap; and single-pot, solid-phase, sample preparation (SP3). We found that SP3 and S-Trap substantially reduced or eliminated the polymer(s), but S-Trap provided the most robust cleanup and highest quality data. Additionally, we observed that SP3 sample preparation of our samples and in other published data sets was associated with partial alkylation of cysteines, which could impact the confidence and robustness of protein identification and quantification. Finally, we observed that several commercial mammalian cell culture media and media supplements also contained polymers with similar mass spectrometry profiles, and we suggest that proteomic analyses in these media will also benefit from the use of S-Trap sample preparation.

Measures of harm reduction service provision for people who inject drugs.

Coverage is an important dimension in measuring the effectiveness of needle and syringe programmes in providing sterile injecting equipment for people who inject drugs. The World Health Organization (WHO), the United Nations Office on Drugs and Crime (UNODC) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) currently recommend methods for measuring coverage at the population level, that is, across an estimated population of people who inject drugs within a given geographical area. However, population-level measures of coverage rely on highly uncertain population estimates and cannot capture the different levels of syringe acquisition and injecting episodes among individual users. Consequently, such measures only broadly evaluate the extent of programme service delivery, rather than describe how people who inject drugs as individuals and sub-groups interact with needle and syringe programmes. In response to these limitations, several researchers have proposed measuring coverage at the individual level, by the percentage of injecting episodes in relation to the number of sterile needles and syringes acquired. These measures evaluate coverage according to each individual's needs. Such measures provide enhanced information for planning and monitoring of harm reduction programmes and have now been used in multiple international research studies. We advise that WHO, UNODC and UNAIDS add individual-level coverage measurement methods to their international monitoring guidelines for harm reduction programmes. By doing this, more responsive and effective programmes can be created to better reduce injecting risk behaviours and blood-borne virus transmission among people who inject drugs.

La couverture est une dimension importante lorsque l'on veut mesurer l'efficacité des programmes de distribution d'aiguilles et de seringues à fournir du matériel d'injection stérile aux consommateurs de drogues par injection. L'Organisation mondiale de la Santé (OMS), l'Office des Nations Unies contre la drogue et le crime (ONUDC) et le Programme commun des Nations Unies sur le VIH/sida (ONUSIDA) recommandent actuellement des méthodes pour mesurer la couverture au niveau de la population, c'est-à-dire sur une population estimée de consommateurs de drogues par injection dans une zone géographique donnée. Or, les mesures de la couverture au niveau de la population se fondent sur des estimations très incertaines de la population et ne permettent pas de refléter les différents degrés d'acquisition de seringues et d'épisodes d'injection chez les usagers. Par conséquent, ces mesures n'évaluent que globalement la portée des programmes au lieu de décrire la manière dont les consommateurs de drogues par injection interagissent, individuellement et en sous-groupes, avec les programmes de distribution d'aiguilles et de seringues. En réponse à ces limitations, plusieurs chercheurs ont proposé de mesurer la couverture au niveau individuel, en calculant le pourcentage d'épisodes d'injection par rapport au nombre d'aiguilles et de seringues stériles acquises. Ces mesures permettent d'évaluer la couverture en fonction des besoins de chaque personne. Ce type de mesures offre des informations plus fiables pour la planification et le suivi des programmes de réduction des risques et il est aujourd'hui utilisé dans plusieurs études de recherche internationales. Nous suggérons à l'OMS, à l'ONUDC et à l'ONUSIDA d'ajouter des méthodes de mesure de la couverture au niveau individuel à leurs directives internationales pour le suivi des programmes de réduction des risques. Cela permettra de mettre au point des programmes plus adaptés et efficaces afin de mieux réduire les comportements à risque liés aux injections ainsi que la transmission de virus par le sang chez les consommateurs de drogues par injection.

La cobertura es un factor importante para medir la eficacia de los programas de agujas y jeringas en el suministro de equipo de inyección estéril para las personas que se inyectan drogas. La Organización Mundial de la Salud (OMS), la Oficina de las Naciones Unidas contra la Droga y el Delito (ONUDD) y el Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA) recomiendan actualmente métodos para medir la cobertura a nivel poblacional, es decir, a través de una población estimada de consumidores de drogas inyectables dentro de una zona geográfica determinada. Sin embargo, las medidas de cobertura a nivel poblacional se basan en estimaciones poblacionales altamente inciertas y no pueden captar los diferentes niveles de adquisición de jeringas y episodios de inyección entre los usuarios individuales. En consecuencia, esas medidas solo miden en términos generales el alcance de la prestación de servicios de los programas, en lugar de describir la forma en que las personas que se inyectan drogas como individuos y subgrupos interactúan con los programas de suministro de agujas y jeringas. En respuesta a estas limitaciones, varios investigadores han propuesto medir la cobertura a nivel individual, por el porcentaje de episodios de inyección en relación con el número de agujas y jeringas estériles adquiridas. Estas medidas miden la cobertura de acuerdo a las necesidades de cada individuo. Estas medidas proporcionan una mejor información para la planificación y el seguimiento de los programas de reducción de daños y se han utilizado actualmente en múltiples estudios de investigación internacionales. Aconsejamos que la OMS, la ONUDD y el ONUSIDA incorporen métodos de medición de la cobertura a nivel individual a sus directrices internacionales de vigilancia de los programas de reducción de daños. De este modo, se pueden crear programas más receptivos y eficaces para reducir mejor los comportamientos de riesgo en el uso de drogas inyectables y la transmisión de virus transmitidos por la sangre entre las personas que se inyectan drogas.

The Prison and Transition Health (PATH) Cohort Study: Study Protocol and Baseline Characteristics of a Cohort of Men with a History of Injecting Drug Use Leaving Prison in Australia.

People who inject drugs (PWID) are disproportionately represented among individuals who experience imprisonment and often have more complex physical and mental health needs than people in prison without injecting histories. The trajectories of PWID after prison release are poorly understood, hampering the development of effective strategies to address their distinct health needs. The Prison and Transition Health (PATH) Cohort Study is characterising the post-release trajectories of incarcerated male PWID in Victoria, Australia. We outline study methodology and baseline characteristics of participants prior to their release. Four hundred participants were recruited from three prisons and completed researcher-administered baseline interviews covering socio-demographics, social supports, physical health, mental health, alcohol and other drug use, and pre-release and transitional service utilisation. The median age among participants was 36 years (IQR 30-42), and they reported a median of five (IQR 3-9) previous adult incarcerations. Almost half (49%) were reliant on government payments prior to incarceration. One quarter (25%) of participants reported removal from their parents' care as children and 64% reported being a parent or primary caregiver to children. Most participants (81%) reported a previous mental health diagnosis and 44% reported three or more diagnoses. The most common drugs injected prior to incarceration were crystal methamphetamine (80%) and heroin (62%), and most (85%) reported being under the influence of drugs at the time of committing offences for which they were currently incarcerated. Injecting drug use during their current sentence was reported by 40% of participants, and 48% reported engaging with some form of drug treatment during their current sentence. Study participants are characterised by significant mental health and substance use morbidities, social disadvantage and criminogenic histories that present challenges for the provision of post-release support services. Data from the PATH Cohort Study will help inform strategies to improve the health and social outcomes of this population.

Acceptability of prison-based take-home naloxone programmes among a cohort of incarcerated men with a history of regular injecting drug use.

BACKGROUND: Take-home naloxone (THN) programmes are an evidence-based opioid overdose prevention initiative. Elevated opioid overdose risk following prison release means release from custody provides an ideal opportunity for THN initiatives. However, whether Australian prisoners would utilise such programmes is unknown. We examined the acceptability of THN in a cohort of male prisoners with histories of regular injecting drug use (IDU) in Victoria, Australia. METHODS: The sample comprised 380 men from the Prison and Transition Health (PATH) Cohort Study; all of whom reported regular IDU in the 6 months prior to incarceration. We asked four questions regarding THN during the pre-release baseline interview, including whether participants would be willing to participate in prison-based THN. We describe responses to these questions along with relationships between before- and during-incarceration factors and willingness to participate in THN training prior to release from prison. RESULTS: Most participants (81%) reported willingness to undertake THN training prior to release. Most were willing to resuscitate a friend using THN if they were trained (94%) and to be revived by a trained peer (91%) using THN. More than 10 years since first injection (adjusted odds ratio [AOR] 2.22, 95%CI 1.03-4.77), having witnessed an opioid overdose in the last 5 years (AOR 2.53, 95%CI 1.32-4.82), having ever received alcohol or other drug treatment in prison (AOR 2.41, 95%CI 1.14-5.07) and injecting drugs during the current prison sentence (AOR 4.45, 95%CI 1.73-11.43) were significantly associated with increased odds of willingness to participate in a prison THN programme. Not specifying whether they had injected during their prison sentence (AOR 0.37, 95%CI 0.18-0.77) was associated with decreased odds of willingness to participate in a prison THN training. CONCLUSION: Our findings suggest that male prisoners in Victoria with a history of regular IDU are overwhelmingly willing to participate in THN training prior to release. Factors associated with willingness to participate in prison THN programmes offer insights to help support the implementation and uptake of THN programmes to reduce opioid-overdose deaths in the post-release period.

The Association between Intentional Overdose and Same-Sex Sexual Intercourse in a Cohort of People who Inject Drugs in Melbourne, Australia.

BACKGROUND: People who inject drugs (PWID) are at disproportionately high risk of suicidal behaviors, as are individuals who report same-sex attraction or experience. However, there is little evidence of compounded risk of suicide for individuals who report same-sex sexual intercourse (SSI) and are PWID. OBJECTIVES: To explore the associations of lifetime intentional overdose amongst a cohort of PWID, with particular attention to those reporting SSI. METHODS: The sample included 529 participants, from an ongoing cohort of 757 PWID. An "ever" SSI variable was created for participants who reported sexual intercourse with a same-sex partner at any longitudinal interview. We explored the adjusted associations between SSI and lifetime intentional overdose using logistic regression. RESULTS: Ninety-one (17%) participants reported ever experiencing an intentional overdose. Forty-one (8%) participants reported SSI at any interview. Three hundred and sixty (68%) participants reported diagnosis of a mental health condition. Diagnosis of a mental health condition (AOR = 2.02, 95% CIs: 1.14, 3.59) and SSI (AOR = 2.58, 95% CIs: 1.22, 5.48) significantly increased the odds of lifetime intentional overdose. Conclusions/Importance: We found a heightened risk of intentional overdose amongst PWID reporting SSI, after controlling for diagnosis of a mental health condition. Services need to be aware of this heightened risk and target interventions appropriately.

Syringe Stockpiling by Persons Who Inject Drugs: An Evaluation of Current Measures for Needle and Syringe Program Coverage.

Needle and syringe program (NSP) coverage is commonly used to assess NSP effectiveness. However, existing measures don't capture whether persons who inject drugs (PWIDs) stockpile syringes, an important and novel aspect of NSP coverage. In this study, we determine the extent of stockpiling in a sample of Australian PWIDs and assess whether including stockpiling enhances NSP coverage measures. As part of the Illicit Drug Reporting System study, PWIDs reported syringes procured and given away, total injections in the last month, and syringes currently stockpiled in 2014. We calculated NSP coverage with and without stockpiling to determine proportional change in adequate NSP coverage. We conducted receiver operating characteristic curve analysis to determine whether inclusion of stockpiled syringes in the measure improved sensitivity in discriminating cases and noncases of risky behaviors. Three-quarters of the sample reported syringe stockpiling, and stockpiling was positively associated with nonindigenous background, stable accommodation, no prison history, longer injecting careers, and more frequent injecting. Compared with previous measures, our measure was significantly better at discriminating cases of risky behaviors. Our results could inform NSP policy to loosen restricted-exchange practice, allowing PWIDs greater flexibility in syringe procurement practices, promoting greater NSP coverage, and reducing PWIDs' engagement in risky behaviors.

Individual-level needle and syringe coverage in Melbourne, Australia: a longitudinal, descriptive analysis.

BACKGROUND: Coverage is used as one indicator of needle and syringe program (NSP) effectiveness. At the individual level, coverage is typically defined as an estimate of the proportion of a person who injects drugs' (PWID) injecting episodes that utilise a sterile syringe. In this paper, we explore levels of individual syringe coverage and its changes over time. METHODS: Data were extracted from 1889 interviews involving 502 participants drawn from the Melbourne drug user cohort study (MIX). We asked questions relating to participants syringe acquisition, distribution and injecting frequency within the two weeks before interview. We created a dichotomous coverage variable that classified participants as sufficiently (≥100 %) covered if all their injecting episodes utilised at least one sterile syringe, and insufficiently (<100 %) covered if not. We categorised participants as "consistently covered" if they were sufficiently covered across interviews; as "consistently uncovered" if they were insufficiently covered across interviews; and "inconsistently covered" if they oscillated between coverage states. Chi-square statistics tested proportions of insufficient coverage across sub-groups using broad demographic, drug use and service utilisation domains. Logistic regression tested predictors of insufficient coverage and inconsistently covered categorisation. RESULTS: Across the sample, levels of insufficient coverage were substantial (between 22-36 % at each interview wave). The majority (50 %) were consistently covered across interviews, though many (45 %) were inconsistently covered. We found strong statistical associations between insufficient coverage and current hepatitis C virus (HCV) infection (RNA+). Current prescription of opioid substitution therapy (OST) and using NSPs as the main source of syringe acquisition were protective against insufficient coverage. CONCLUSION: Insufficient coverage across the sample was substantial and mainly driven by those who oscillated between states of coverage, suggesting the presence of temporal factors. We recommend a general expansion of NSP services and OST prescription to encourage increases in syringe coverage.

The impact of injecting networks on hepatitis C transmission and treatment in people who inject drugs.

UNLABELLED: With the development of new highly efficacious direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV), the concept of treatment as prevention is gaining credence. To date, the majority of mathematical models assume perfect mixing, with injectors having equal contact with all other injectors. This article explores how using a networks-based approach to treat people who inject drugs (PWID) with DAAs affects HCV prevalence. Using observational data, we parameterized an exponential random graph model containing 524 nodes. We simulated transmission of HCV through this network using a discrete time, stochastic transmission model. The effect of five treatment strategies on the prevalence of HCV was investigated; two of these strategies were (1) treat randomly selected nodes and (2) "treat your friends," where an individual is chosen at random for treatment and all their infected neighbors are treated. As treatment coverage increases, HCV prevalence at 10 years reduces for both the high- and low-efficacy treatment. Within each set of parameters, the treat your friends strategy performed better than the random strategy being most marked for higher-efficacy treatment. For example, over 10 years of treating 25 per 1,000 PWID, the prevalence drops from 50% to 40% for the random strategy and to 33% for the treat your friends strategy (6.5% difference; 95% confidence interval: 5.1-8.1). CONCLUSION: Treat your friends is a feasible means of utilizing network strategies to improve treatment efficiency. In an era of highly efficacious and highly tolerable treatment, such an approach will benefit not just the individual, but also the community more broadly by reducing the prevalence of HCV among PWID.

Patterns of, and Factors Associated With, Illicit Pharmaceutical Opioid Analgesic Use in a Prospective Cohort of People Who Inject Drugs in Melbourne, Australia.

BACKGROUND: People who inject drugs (PWID) are a key population engaging in pharmaceutical opioid analgesic (PO) use, yet little is known about patterns of illicit PO use among this group. OBJECTIVES: The aims of this research were to measure the prevalence and frequency of lifetime and past-month illicit PO use and injection in a sample of regular PWID, to examine patterns of past-month illicit PO use within individuals over time, and to identify factors independently associated with past-month illicit PO use. METHODS: Data were drawn from a prospective cohort study of regular PWID (N = 666) in Melbourne, Australia. Data from five waves of annual data collection (including baseline) were analyzed descriptively and using generalized estimating equations (GEE). RESULTS: At baseline, 59% of participants reported lifetime illicit PO use and 20% reported past-month use, predominantly through injecting. Most illicit PO users at baseline transitioned to nonuse of illicit POs across the study period. In multivariable GEE analysis, factors associated with past-month illicit PO use included past-year arrest [adjusted odds ratio (AOR): 1.39], opioids other than heroin as drug of choice (AOR: 5.14), experiencing poorer physical health (AOR: 0.98) and a range of other drug use variables. CONCLUSIONS: We found little evidence of ongoing illicit PO use among those followed up, with illicit PO use linked to polydrug use more broadly. Nonetheless, trends in illicit PO use among PWID should continue to be monitored and harm reduction interventions implemented to reduce the associated public health risks.

Antigen-driven patterns of TCR bias are shared across diverse outcomes of human hepatitis C virus infection.

Hepatitis C virus (HCV) infection causes significant morbidity and mortality worldwide. T cells play a central role in HCV clearance; however, there is currently little understanding of whether the disease outcome in HCV infection is influenced by the choice of TCR repertoire. TCR repertoires used against two immunodominant HCV determinants--the highly polymorphic, HLA-B*0801 restricted (1395)HSKKKCDEL(1403) (HSK) and the comparatively conserved, HLA-A*0101-restricted, (1435)ATDALMTGY(1443) (ATD)--were analyzed in clearly defined cohorts of HLA-matched, HCV-infected individuals with persistent infection and HCV clearance. In comparison with ATD, TCR repertoire selected against HSK was more narrowly focused, supporting reports of mutational escape in this epitope, in persistent HCV infection. Notwithstanding the Ag-driven divergence, T cell repertoire selection against either Ag was comparable in subjects with diverse disease outcomes. Biased T cell repertoires were observed early in infection and were evident not only in persistently infected individuals but also in subjects with HCV clearance, suggesting that these are not exclusively characteristic of viral persistence. Comprehensive clonal analysis of Ag-specific T cells revealed widespread use of public TCRs displaying a high degree of predictability in TRBV/TRBJ gene usage, CDR3 length, and amino acid composition. These public TCRs were observed against both ATD and HSK and were shared across diverse disease outcomes. Collectively, these observations indicate that repertoire diversity rather than particular Vß segments are better associated with HCV persistence/clearance in humans. Notably, many of the anti-HCV TCRs switched TRBV and TRBJ genes around a conserved, N nucleotide-encoded CDR3 core, revealing TCR sequence mosaicism as a potential host mechanism to combat this highly variant virus.

Hepatitis B virus exposure and vaccination in a cohort of people who inject drugs: what has been the impact of targeted free vaccination?

BACKGROUND AND AIM: Forty percent of new hepatitis B virus (HBV) infections in Australia occur in people who inject drugs (PWID); long-term infection carries the risk of serious liver disease. HBV incidence among Australian PWID has not been measured since the advent of targeted (2001) and adolescent school-based "catch-up" (1998) vaccination programs. We measured HBV incidence and prevalence in a cohort of PWID in Melbourne, Australia and examined demographic and behavioral correlates of exposure and vaccination. METHODS: Community-recruited PWID were surveyed about blood-borne virus risk behaviors and their sera tested for HBV markers approximately three-monthly over three years. Incidence was assessed using prospectively collected data. A cross-sectional design was used to examine prevalence of HBV exposure and vaccination at baseline. Poisson regression was used to identify correlates of HBV exposure and vaccination. RESULTS: At baseline, 33.1% of participants (114/344) had been vaccinated against HBV, 40.4% (139/344) had been exposed (previously or currently infected), and 26.5% (91/344) were susceptible. HBV incidence was 15.7 per 100 person-years. Independent associations with HBV exposure included female gender, South-East Asian ethnicity, drug treatment in the past three months, injecting in prison, and prior exposure to hepatitis C virus. Independent associations with vaccination included being ≤ 25 years old, reporting HBV vaccination, and never having been to prison. CONCLUSIONS: HBV infection continues at high incidence among Australian PWID despite the introduction of free vaccination programs. Innovative methods are needed to encourage PWID to complete HBV vaccination.

Establishing the Melbourne Injecting Drug User Cohort Study (MIX): rationale, methods, and baseline and twelve-month follow-up results.

BACKGROUND: Cohort studies provide an excellent opportunity to monitor changes in behaviour and disease transmission over time. In Australia, cohort studies of people who inject drugs (PWID) have generally focused on older, in-treatment injectors, with only limited outcome measure data collected. In this study we specifically sought to recruit a sample of younger, largely out-of-treatment PWID, in order to study the trajectories of their drug use over time. METHODS: Respondent driven sampling, traditional snowball sampling and street outreach methods were used to recruit heroin and amphetamine injectors from one outer-urban and two inner-urban regions of Melbourne, Australia. Information was collected on participants' demographic and social characteristics, drug use characteristics, drug market access patterns, health and social functioning, and health service utilisation. Participants are followed-up on an annual basis. RESULTS: 688 PWID were recruited into the study. At baseline, the median age of participants was 27.6 years (IQR: 24.4 years - 29.6 years) and two-thirds (67%) were male. Participants reported injecting for a median of 10.2 years (range: 1.5 months - 21.2 years), with 11% having injected for three years or less. Limited education, unemployment and previous incarceration were common. The majority of participants (82%) reported recent heroin injection, and one third reported being enrolled in Opioid Substitution Therapy (OST) at recruitment. At 12 months follow-up 458 participants (71% of eligible participants) were retained in the study. There were few differences in demographic and drug-use characteristics of those lost to follow-up compared with those retained in the study, with attrition significantly associated with recruitment at an inner-urban location, male gender, and providing incomplete contact information at baseline. CONCLUSIONS: Our efforts to recruit a sample of largely out-of-treatment PWID were limited by drug market characteristics at the time, where fluctuating heroin availability has led to large numbers of PWID accessing low-threshold OST. Nevertheless, this study of Australian injectors will provide valuable data on the natural history of drug use, along with risk and protective factors for adverse health outcomes associated with injecting drug use. Comprehensive follow-up procedures have led to good participant retention and limited attrition bias.

A cross-sectional study of emergency department visits by people who inject drugs.

BACKGROUND: People who inject drugs (PWID) have worse health than non-injectors and are at heightened risk of incidents that necessitate hospital emergency department (ED) visits. STUDY OBJECTIVES: To describe ED visits by PWIDs in Melbourne, Australia, and compare reasons with those given in Vancouver, Canada. METHODS: In 2008-2010, 688 Melbourne PWIDs were interviewed about their ED visits; these data were contrasted with published data about ED visits by PWIDs in Vancouver. RESULTS: Participants reported 132 ED visits in the month preceding interview--27.3% drug-related, 20.5% trauma-related (principally physical assault), 13.6% for psychiatric problems. Melbourne PWIDs are less likely to attend ED for soft-tissue injuries, and more likely to attend after physical assault than PWIDs in Vancouver. CONCLUSION: PWID in Melbourne and Vancouver attend EDs for different reasons; information about PWID visits can help EDs cater for them and provide insights for prevention.

The more you look, the more you find: effects of hepatitis C virus testing interval on reinfection incidence and clearance and implications for future vaccine study design.

INTRODUCTION: Studies have explored whether spontaneous clearance of hepatitis C virus (HCV) infection decreases the likelihood of reinfection or increases the probability of clearance. This analysis investigates whether the conflicting findings from these studies could be due to differences in frequency of HCV RNA testing. METHODS: A model simulated the dynamics of HCV reinfection and clearance among a cohort of injection drug users. For different reinfection incidence and clearance rates, the model evaluated the accuracy of epidemiological studies that used different HCV testing frequencies. RESULTS: Experimental estimates for the reinfection incidence and clearance probability will be accurate (<20% error) if the testing interval is less than the reinfection clearance duration. Otherwise, experimental estimates can greatly underestimate the real values (≤66% error if reinfection duration is 1 month and the testing interval is 3 months). Uncertainty in experimental estimates also increases at lower reinfection incidences, whereas for lower clearance probabilities the uncertainty in the estimated clearance probability increases but estimated reinfection incidence decreases. DISCUSSION: Differences in HCV testing interval could account for most between-study variability in the estimated probability of clearing reinfections and is likely to have biased reinfection incidence estimates. Our findings suggest that a high reinfection clearance probability (>75%) is consistent with data.

Trends in sexual behavior, testing, and knowledge in young people; 2006-2011.

Cross-sectional surveys were conducted annually from 2006 to 2011 at a music festival. Eight thousand one hundred sixty-five young people completed surveys. STI testing rates increased over time, but there was an increase in the prevalence of some sexual risk behaviors and little improvement in STI knowledge between 2006 and 2011.