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The authors discuss a study published within the issue which showed that using direct-acting antiviral (DAA) therapy to treat hepatitis C infection in many European countries is unlikely to have a substantive impact on hepatitis C incidence and prevalence among people who inject drugs (PWID) unless treatment rates are increased. Topics include the implication of the study for many countries, barriers to treatment, and the importance of robust hepatitis surveillance systems.

Background. The Australian Trial in Acute Hepatitis C (ATAHC) is a National Institutes of Health--funded prospective cohort study of the natural history and efficacy of treatment in individuals with recently acquired hepatitis C. Enrollment is open to both human immunodeficiency virus (HIV)--infected and -uninfected individuals. The aim of this article was to evaluate characteristics and virological outcomes among HIV-infected individuals enrolled in ATAHC. Methods. Eligibility criteria included the first positive result of testing for anti-hepatitis C virus (HCV) antibody within 6 months and either clinical hepatitis diagnosed within the past 12 months or documented anti-HCV seroconversion within the past 24 months. Results. Of the initial 103 patients enrolled, 27 (26%) were HIV infected. HIV-infected patients were more likely to be older, to have HCV genotype 1 infection and high levels of HCV RNA at baseline than were HCV-monoinfected patients. Sexual acquisition accounted for the majority (56%) of HCV infections among HIV-infected patients, compared with only 8% of HCV-monoinfected patients. The median duration from estimated HCV infection to treatment was 30 weeks. Treatment with 24 weeks of pegylated interferon and ribavirin resulted in rates of undetectability of HCV RNA of 95%, 90%, and 80% at weeks 12, 24, and 48, respectively. Undetectability at week 4 was achieved in 44% of patients and yielded positive and negative predictive values for sustained virological response of 100% and 33%, respectively. Conclusions. Significant differences were demonstrated between HIV-infected and HIV-uninfected individuals enrolled in ATAHC. Treatment responses among HIV-infected individuals with both acute and early chronic infection are encouraging and support regular HCV screening of high-risk individuals and early treatment for recently acquired HCV infection. [ABSTRACT FROM AUTHOR]

Noroviruses are a major cause of both sporadic and epidemic gastroenteritis in humans, but the mechanisms by which norovirus circulates within the community are poorly understood. In this study, we examined the hypothesis that asymptomatic people act as a reservoir for norovirus. Faecal specimens from 399 asymptomatic individuals were tested for norovirus by reverse transcription polymerase chain reaction (RT-PCR) methodology, and no norovirus was detected. The failure to detect norovirus was not apparently due to the test sample being resistant to norovirus infection, nor to the presence of PCR inhibitors in the test sample. The findings suggest that, if norovirus is carried by asymptomatic people, the carriage rate is very low; the upper bound (95% confidence interval, binomial distribution) of the carriage rate was only 0.8%. Thus, it is unlikely that asymptomatic people are an important reservoir for norovirus. [ABSTRACT FROM AUTHOR]

AbstractBackground and Aims: The objective of this study was to describe the prevalence of pathogenic microorganisms in asymptomatic individuals in a community study in Melbourne, Australia. Methods: The study population was a subset of 2803 individuals participating in the Water Quality Study; a community based randomized trial. Faecal specimens (1091) were collected over a 3-month period from asymptomatic individuals. Specimens were tested for a range of bacteria including Salmonella, Shigella and Campylobacter species. Rotavirus and adenovirus were detected using a Rota-Adeno latex kit, and protozoa were detected using a permanent stain (modified iron-haemotoxylin). Results: Twenty-eight known pathogens were identified from the 1091 faecal specimens, a total carriage rate of 2.6%. Giardia species were present in 18 specimens (1.6%), Salmonella in four (0.4%), Campylobacter in one (0.1%), Cryptosporidium in four (0.4%) and adenovirus in one (0.1%). Blastocystis hominis was found in 65 specimens. The median age of those without a pathogen was 12.5 years compared with 6.6 years for those with a pathogen (P = 0.02). Conclusions: Except for Giardia, pathogens were rarely found in asymptomatic individuals in the community. The prevalence of pathogens was higher in children than adults. © 2000 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Cryptosporidiosis is a devastating illness in people with HIV/AIDS yet there have been no analytical epidemiological studies measuring risk factors leading to cryptosporidiosis in men who have sex with men (MSM). The objective of this study was to measure the risk factors for exposure to Cryptosporidium among MSM.Methods: The study was a case-control design. It recruited MSM who had laboratory confirmed Cryptosporidium infection between 1997 and 2000. Participants answered a questionnaire about potential risk factors leading to exposure to Cryptosporidium.Results: 10 cases and 24 controls were recruited. Men having more than one sexual partner in the past month were more likely to have had Cryptosporidium diarrhoea p=0.034 (OR 6.67, CI (1.15 to 38.60). Insertive anal sex (p=0.059) and attending a sex venue one or more times (p=0.059) also increased the odds of having cryptosporidiosis.Conclusion: The study results suggest that sexual behaviour is a significant risk factor for cryptosporidial diarrhoea in MSM. The results will be used to inform risk groups about behaviours that may put them at increased risk of cryptosporidial diarrhoea. [ABSTRACT FROM AUTHOR]

Background: Gay, bisexual and other men who have sex with men (GBMSM) are overrepresented in cohorts of people who inject drugs. GBMSM's substance use is usually explored in the context of its contribution to sexual risk. We examined drug use practices, connectedness to other people who inject drugs, peer-to-peer injecting, and access to care among men who inject drugs in Melbourne, Australia. We aim to describe similarities and differences in these parameters for GBMSM and other men. Methods: Data were drawn from a prospective cohort study of people who inject drugs conducted in Melbourne, Australia, since 2009. This cross-sectional study used data collected between 2016 and 2021. Descriptive statistics were used to assess differences between GBMSM and other men. Results: Of 525 men who injected drugs over the study period, 48 (9%) identified as gay or bisexual, or reported sex with other men in the past 12 months. GBMSM and other men reported similar socio-demographics, drug practices (age of injecting initiation, most injected drug, peer-to-peer injecting, receptive syringe sharing) and access to injecting-specific care (drug treatment, source of needle-syringes). A significantly greater percentage of GBMSM reported past 12-month hepatitis C testing (69% vs. 52%, p = 0.028) and preferring methamphetamine (31% vs. 16%, p = 0.022). A higher percentage of GBMSM reported knowing > 50 other people who inject drugs (46% vs. 37%), but this difference was not statistically significant. Both groups primarily obtained injecting equipment from needle-syringe programs; a minority had accessed injecting-specific primary care. Conclusion: Men who injected drugs in this cohort and those who identified as GBMSM reported similar drug and health-seeking practices. The higher prevalence of methamphetamine injecting among GBMSM may warrant different harm reduction support for this group. Health promotion should utilise opportunities to connect men who inject drugs in Melbourne to injecting-specific primary health care. [ABSTRACT FROM AUTHOR]

Summary. The critical events in clearance or persistence of hepatitis C virus (HCV) infection are unknown but likely to be determined early in acute infection. Type 1 and type 2 cytokine production was assessed by HCV peptide ELISpot and multiplex in vitro cytokine production assays in longitudinally collected samples from 20 untreated participants enrolled in the Australian Trial in Acute Hepatitis C (ATAHC); a prospective cohort of acute HCV infection (77% injecting drug users, IDU). Significantly higher interleukin-10 (IL-10) production ( P = 0.048), in the relative absence of interferon-gamma (IFN-γ) and IL-2 production, was present early in HCV infection in those who progressed to chronic infection. In contrast, viral clearance was associated with a greater magnitude and broader specificity of IFN-γ (magnitude P < 0.001, breadth P = 0.004) and IL-2 responses, in the relative absence of IL-10. Early IL-10 production was correlated with higher HCV RNA level at baseline ( P = 0.046) and week 12 ( P = 0.018), while IFN-γ and IL-2 production was inversely correlated with HCV RNA level at baseline (IFN-γ P = 0.020, IL-2 P = 0.050) and week 48 (IFN-γ P = 0.045, IL-2 P = 0.026). Intracellular staining (ICS) indicated the HCV-specific IFN-γ response was primarily from CD8+ T cells and NK cells, whereas IL-10 production was predominantly from monocytes, with a subset of IL-10 producing CD8+ T cells present only in those who progressed to chronic infection. IL-10, an immunoregulatory cytokine, appears to play a key role in progression to chronic HCV infection. [ABSTRACT FROM AUTHOR]

HCV transmission networks within the Australian Trial in Acute Hepatitis C occurred predominantly in HIV positive populations and almost exclusively in men who have sex with men. Both sexual and injecting drug use risk were observed within the same clusters.Background. Injecting drug users remain the population at greatest risk of acquiring hepatitis C virus (HCV) infection, although a recent increase in cases of sexually transmitted HCV infection has been observed among human immunodeficiency virus (HIV)–infected individuals. The extent to which these separate epidemics overlap is unknown.Methods. The Australian Trial in Acute Hepatitis C (ATAHC) enrolled 163 individuals (29% of whom were HIV infected) with recent HCV infection. E1/HVR1 sequences were used to construct phylogenetic trees demonstrating monophyletic clusters or pairs, and viral epidemic history and phylogeography were assessed using molecular clock analysis. Individual clusters were characterized by clinical and demographic characteristics.Results. Transmission through injection drug use occurred for 73% of subjects, with sexual transmission occurring for 18% (92% of whom were HIV infected). Among 112 individuals with available E1/HVR1 sequences, 23 (20%) were infected with a strain of HCV identical to that of another subject, comprising 4 homologous clusters and 3 monophyletic pairs, the majority of which (78%) were HIV infected. Clusters contained individuals with both injection drug use–related and sex-related acquisition, and in all clusters (except for 1 female HIV-uninfected pair), individuals identified as men who have sex with men, irrespective of HIV status.Conclusions. This large unique study of HIV-infected and HIV-uninfected individuals with recently acquired HCV infection demonstrates that clustering is common in the HIV-infected population and that it occurred almost invariably among men who have sex with men, irrespective of the actual mode of acquisition. These findings suggest the coexistence of both injection drug use and sexual risk behaviors for individuals in the same social networks and have implications for the development of public health messages.Clinical trial registration. NCT00192569. [ABSTRACT FROM AUTHOR]

• Australian prevalence of baseline HCV GT1a NS5A RAS was 7%, lower than other countries. • The prevalence of NS5A RAS in GT1b and GT3 HCV is comparable to international data. • Next generation sequencing has limited utility over population sequencing at baseline. Direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) treatment, and most regimens include an NS5A inhibitor. Certain amino-acid substitutions confer resistance to NS5A inhibitors, termed resistance-associated substitutions (RAS). If present at baseline, they can reduce virological response rates. Population-based sequencing (PBS) is generally used for baseline sequencing, however next generation sequencing (NGS) reduces the threshold for detection of sequences encoding RAS from 20% to 5%. We determined the prevalence of NS5A RAS at baseline amongst Australian chronically infected with genotype (GT)1a, GT1b and GT3 HCV, using both PBS and NGS. Samples from DAA-naïve individuals were received at the Victorian Infectious Disease Reference Laboratory between June 2016 and December 2018. All samples were analysed for NS5A RAS using PBS. A subset of GT1 HCV samples were processed using NGS technology (Vela Diagnostics, Singapore) to determine the improvement in sensitivity. In total, 672 samples were analysed using PBS. The baseline prevalence of NS5A RAS was 7.6% for GT1a (n = 25/329), 15.7% for GT1b (n = 8/51) and 15.1% for GT3 (n = 44/292). NGS only marginally increased sensitivity for NS5A RAS at baseline in GT1a (16% vs 17%) and GT1b (29% vs 36%). The prevalence of NS5A RAS in GT1a HCV in Australia was low compared with international data, and was similar to other reported international prevalence for GT1b and GT3 infection. NGS at baseline only marginally increased sensitivity for the detection of NS5A RAS in patients with GT1 HCV and cannot be recommended for routine use at baseline in clinical practice. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The patient's journey with chronic hepatitis C from interferon plus ribavirin to interferon- and ribavirin-free regimens: a study of health-related quality of life" that was published in a previous issue of the periodical.

Summary: To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct‐acting antivirals (DAAs) to treat hepatitis C virus (HCV)—in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule prescription data were used to evaluate GP DAA prescription 12 months pre‐and post‐ pathway implementation. A retrospective review of patients referred for remote consultation for 12 months post‐ pathway inception was undertaken to determine the care cascade. HCV treatment initiation by GPs increased after implementation of the remote consultation pathway. In the 12‐month study period, 74 GPs referred 169 people for remote consultation; 114 (67%) were approved for GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119 (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post‐treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15 achieved SVR ranging from week 5 to 11 post‐treatment. No treatment failure was detected. Collaborative development and implementation of a remote consultation pathway has engaged regional GPs in managing HCV. Follow‐up post‐treatment could be improved; however, no treatment failure has been documented. To eliminate HCV as a public health threat, it is vital that specialists support GPs to prescribe DAA. [ABSTRACT FROM AUTHOR]

A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879. [ABSTRACT FROM AUTHOR]

Inadequate response to injecting drug use ( IDU) is a significant problem the world over. Low levels of funding, political inaction, poor levels of health service coverage, high prevalence and incidence of IDU-related blood-borne viruses ( BBVs) and ongoing stigmatization/marginalization affect people who inject drugs ( PWID) regardless of the income status of the country they reside in. These barriers and system failings are, however, exacerbated in low and middle-income countries ( LMICs), meaning that the potential consequences of inaction are more pressing. In this narrative review, we describe the levels of IDU and IDU-specific BBV prevalence in LMICs; levels of harm reduction implementation; the consequences of late or insufficient response, the shortcomings of data collection and dissemination; and the barriers to effective LMIC harm reduction implementation. We also exemplify cases where IDU-related harms and BBV epidemics have been successfully curtailed in LMICs, showing that effective response, despite the barriers, is possible. In conclusion, we suggest four key priorities on the basis of the review: confirming the presence or absence of IDU in LMICs, improving the collection and dissemination of national IDU-specific data, increasing the level of harm reduction programme implementation in LMICs, and increasing both national and international advocacy for PWID and attendant public health interventions. [ABSTRACT FROM AUTHOR]

One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core-E2 and/or NS5B regions. Reinfection incidence was calculated using person-time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection ( n=120; 83% male; median age 36 years) was composed of HIV-positive men-who-have-sex-with-men (53%) and people who inject drugs (current 49%, ever 69%). Total follow-up time at risk was 135 person-years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post-treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age ( aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post-treatment ( aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post-treatment surveillance, harm reduction strategies and education in at-risk populations. [ABSTRACT FROM AUTHOR]

Combining phylogenetic and network methodologies has the potential to better inform targeted interventions to prevent and treat infectious diseases. This study reconstructed a molecular transmission network for people with recent hepatitis C virus ( HCV) infection and modelled the impact of targeting directly acting antiviral ( DAA) treatment for HCV in the network. Participants were selected from three Australian studies of recent HCV from 2004 to 2014. HCV sequence data (Core-E2) from participants at the time of recent HCV detection were analysed to infer a network by connecting pairs of sequences whose divergence was ≤.03 substitutions/site. Logistic regression was used to identify factors associated with connectivity. Impact of targeting HCV DAAs at both HIV co-infected and random nodes was simulated (1 million replicates). Among 236 participants, 21% (n=49) were connected in the network. HCV/ HIV co-infected participants (47%) were more likely to be connected compared to HCV mono-infected participants (16%) ( OR 4.56; 95% CI; 2.13-9.74). Simulations targeting DAA HCV treatment to HCV/ HIV co-infected individuals prevented 2.5 times more onward infections than providing DAAs to randomly selected individuals. Results demonstrate that genetic distance-based network analyses can be used to identify characteristics associated with HCV transmission, informing targeted prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Several direct-acting antivirals ( DAAs) have been approved for the treatment of chronic hepatitis C virus ( HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions ( RASs) have been reported both in treatment-naïve patients and following treatment with protease ( NS3), phosphoprotein ( NS5A) and polymerase ( NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 ( GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes ( GT1- GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. [ABSTRACT FROM AUTHOR]

Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities. [ABSTRACT FROM AUTHOR]

Background: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. Methods: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. Discussion: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men. [ABSTRACT FROM AUTHOR]

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response ( SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent ( n = 38) were HIV/ HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/ HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL ( aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years ( vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making. [ABSTRACT FROM AUTHOR]

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC3 study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males ( vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection ( vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex ( vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 ( IFNL4) rs12979860 CC genotype ( vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection ( vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 ( vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) testing and counselling have the potential to impact individual behaviour and transmission dynamics at the population level. Evidence of the impact of an HCV-positive status notification on injection risk reduction is limited. The objective of our study was to (1) assess drug and alcohol use and injection risk behaviours following notification; (2) to compare behaviour change in people who inject drugs (PWID) who received a positive test result and those who remained negative; and (3) to assess the effect of age on risk behaviour. Methods Data from the International Collaboration of Incident HIV and HCV Infection in Injecting Cohorts (InC3 Study) were analysed. Participants who were initially HCV seronegative were followed prospectively with periodic HCV blood testing and post-test disclosure and interview-administered questionnaires assessing drug use and injection behaviours. Multivariable generalised estimating equations were used to assess behavioural changes over time. Results Notification of an HCV-positive test was independently associated with a small increase in alcohol use relative to notification of a negative test. No significant differences in postnotification injection drug use, receptive sharing of ancillary injecting equipment and syringe borrowing postnotification were observed between diagnosis groups. Younger PWID receiving a positive HCV test notification demonstrated a significant increase in subsequent alcohol use compared with younger HCV negative. Conclusions The proportion of PWID reporting alcohol use increased among those receiving an HCV-positive notification, increased the frequency of alcohol use postnotification, while no reduction in injection drug use behaviours was observed between notification groups. These findings underscore the need to develop novel communication strategies during post-test notification to improve their impact on subsequent alcohol use and risk behaviours. [ABSTRACT FROM AUTHOR]

Background: Gay and bisexual men (GBM) have higher substance use prevalences than general population samples - often attributed to stigmatisation of sexual minority identities. We examined how influential public health research on substance use among GBM interprets this behaviour and what GBM-specific identities emerge through the discourses employed.Methods: We searched Web of Science for publications on substance use among GBM, selecting 60 of the most cited papers published during 2000-2020. We studied the language used to describe and interpret drug-using behaviour using critical discourse analysis, focusing on interpretive repertoires and subject positions.Results: Three distinct discursive tendencies were identified. First, in constructing a target population, GBM who use illicit drugs are positioned as deficient, socially irresponsible, and maladapted to dealing with stigmatisation and HIV risks. Second, in shifting the focus beyond the individual, the gay community is conceptualised as offering a safe space for socialisation. Nonetheless, gay community spaces are problematised as promoting substance use among vulnerable GBM through aggravating loneliness and normalising drug use as a form of maladaptive (avoidance) coping. Third, counterdiscursive movements add nuance, context, and comparisons that relativise rather than generalise substance use and focus on pleasure and self-determination. Such discourses centre the need for interventions that disrupt homophobic socio-structures instead of individualising approaches to limit non-conformity.Conclusion: 'Expert' assessments of substance use among GBM perpetuate pathologising understandings of this behaviour and promote abject subject positions, contributing to perpetuations of intergroup stigma and social exclusion based on drug and sexual practices. Our findings highlight the need for deliberate and critical engagement with prior research and a conscious effort to disrupt dominant discourses on GBM's substance use. [ABSTRACT FROM AUTHOR]

Men who have sex with men are a priority population for HIV control in Laos, but encompass men diverse in sexual orientation, gender identification, and behavior. Behaviorally bisexual men and their sexual partners were recruited in Vientiane, Laos, in 2010 using modified snowball sampling. Heterosexual-identifying bisexual men identified as exclusively/predominantly heterosexual and other bisexual men identified as bisexual or predominantly/exclusively homosexual. Sixty (68%) heterosexual-identifying and 38 (32%) other bisexual men were recruited; the median number of sex partners in the past year was eight and seven, respectively. Consistent condom use was low with regular (7%) and casual (35%) partners and did not differ by identity. More heterosexual-identifying (53%) than other bisexual (29%) men reported weekly alcohol consumption. Twelve (20%) heterosexual-identifying and 15 (54%) other bisexual men correctly answered all HIV-knowledge questions. High-risk behaviors for STI and HIV transmission were common. Targeted HIV prevention initiatives are needed, particularly to reach heterosexual-identifying bisexual men. [ABSTRACT FROM AUTHOR]

Abstract: Background: There has been a significant increase in the provision of injecting paraphernalia from Scottish injecting equipment provision (IEP) services. However, there is currently a lack of evidence on whether uptake of paraphernalia has any impact on paraphernalia sharing among injecting drug users (IDU). The aim of this study was to examine the factors associated with paraphernalia sharing; in particular, whether uptake of filters, spoons and sterile water from IEPs is associated with a reduction in the sharing of these items. Methods: A cross-sectional voluntary anonymous survey of 2037 IDUs was administered during 2008–2009. Participants were asked whether they had shared filters, spoons or water (paraphernalia) in the previous 6months, and their uptake of these items from an IEP during an average week in the previous 6months. Results: Self-reported uptake of paraphernalia in an average week during the previous 6months was associated with reduced odds of sharing paraphernalia: (i) uptake of >30 filters was associated with a reduced odds of sharing filters (adjusted odds ratio (AOR) 0.50, 95% confidence interval 0.32–0.79); (ii) uptake of >30 spoons was associated with a reduced odds of sharing spoons (AOR 0.46, 95% confidence interval 0.28–0.74); and (iii) uptake of sterile water was associated with a reduced odds of sharing water (AOR 0.36, 95% confidence interval 0.22–0.61) compared to no uptake of each of these items. Conclusions: Uptake of paraphernalia appears to be associated with safer injecting practice. Further research is needed to establish the impact of paraphernalia provision on HCV transmission. [Copyright &y& Elsevier]

Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4(+) T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534). [ABSTRACT FROM AUTHOR]

BACKGROUND: A systematic review was conducted to determine whether behavioural interventions are effective in preventing transmission of hepatitis C virus (HCV) amongst people who inject drugs. METHODS: Medline, EMBASE, the Cochrane Clinical Trial Database, PSYCHINFO and hand-searching of bibliographies were used to identify controlled trials of behavioural interventions for reducing HCV transmission amongst people who inject drugs. Behavioural interventions were defined as non-pharmacological interventions that aimed to change individual behaviours without explicitly attempting to change population norms. RESULTS: Six trials evaluating peer-education training and counselling interventions were included in the review. There was considerable variation between trials with respect to intervention duration, control and study population. Trials evaluated the impact of interventions on HCV incidence (three studies, 1041 participants) and frequency of injecting risk behaviours (six studies, 2472 participants). Amongst the three studies which measured the impact of the intervention on HCV incidence, none found a statistically significant difference between intervention and control groups. Measures of frequency of injecting risk behaviours varied greatly and could not be pooled. Only two studies (n=418, 854) showed significantly greater reductions in injecting risk behaviours in the intervention group compared with the control group. CONCLUSIONS: There was considerable variation in study design, outcome measures and magnitude, direction and statistical significance of findings between studies. Nonetheless, it is unlikely that behavioural interventions can have a considerable effect on HCV transmission. It is likely that multi-component interventions are required. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis C virus (HCV) is a blood-borne virus that disproportionately affects people who inject drugs (PWIDs). Based on extensive interview and blood test data from a longitudinal study in Melbourne, Australia, we describe an individual-based transmission model for HCV spread amongst PWID. We use this model to simulate the transmission of HCV on an empirical social network of PWID. A feature of our model is that sources of infection can be both network neighbours and non-neighbours via “importing”. Data-driven estimates of sharing frequency and rate of importing are provided. Compared to an appropriately calibrated fully connected network, the empirical network provides some protective effect on the time to primary infection. We also illustrate heterogeneities in incidence rate of infection, both across and within node degrees (i.e., number of network partners). We explore the reduced risk of infection from spontaneously clearing cutpoint nodes whose infection status oscillates, both in theory and in simulation. Further, we show our model-based estimate of per-event transmission probability largely agrees with previous estimates at the lower end of the range 1–3% commonly cited. [Copyright &y& Elsevier]

Abstract: Despite that the majority of hepatitis C virus (HCV) infection occurs among injection drug users (IDUs), little is known about HCV treatment uptake in this group, particularly during recent infection. We evaluated uptake of treatment for recent HCV infection, including associated factors, within a population predominantly made up of IDUs. The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV infection. All participants with detectable HCV RNA at screening were offered HCV treatment, assessed for eligibility and those initiating treatment were identified. Logistic regression analyses were used to identify predictors of HCV treatment uptake. Between June 2004 and February 2008, 163 were enrolled, with 146 positive for HCV RNA at enrolment. The mean age was 35 years, 77% (n =113) participants had ever injected illicit drugs and 23% (n =34) reported having ever received methadone or buprenorphine treatment. The uptake of HCV treatment was 76% (111 of 146) among those who were eligible on the basis of positive HCV RNA. Estimated duration of HCV infection (OR=1.03 per week, 95% CI=1.00–1.06, P =0.035) and log10 HCV RNA (OR=1.92 per log10 increase, 95% CI=1.36–2.73, P <0.001) were independently associated with treatment uptake whereas injection drug use was not. This study demonstrates that a high uptake of HCV treatment can be achieved among participants with recently acquired HCV infection. Decisions about whether to initiate treatment for recently acquired HCV were mainly driven by clinical factors, rather than factors related to sociodemographics or injecting behaviors. [Copyright &y& Elsevier]

BACKGROUND: Evidence of harms associated with temazepam gel capsule injecting among injecting drug users in Australia led to its withdrawal from manufacture in Australia. Subsequently, diphenhydramine gel capsule injecting was identified among a subset of ethnic Vietnamese injecting drug users. METHODS: Observational fieldwork around an active street-based illicit drug marketplace together with targeted purposive sampling enabled 66 ethnic Vietnamese injecting drug users to be recruited for in-depth interview. RESULTS: Data revealed that the injection of gel capsules increases exposure to non-viral infections. Analysis of participant interviews show how participants have established their own ways of reducing these harms including thinning the drug solution by jacking regularly during injection. Controversially, femoral vein administration of diphenhydramine-heroin cocktails was also seen as a harm reduction strategy by participants. DISCUSSION: Health education campaigns to address the potentially negative consequences of gel capsule groin injection will not be successful unless health workers and policy makers work with drug users and incorporate local understandings and meanings of risk in health promotion activities. [ABSTRACT FROM AUTHOR]

Background: A social marketing campaign ran in 2004 in the Victoria to increase rates of HIV/sexually transmissible infection (STI) testing among men having sex with men (MSM). Methods: To evaluate the initiative data from HIV sentinel surveillance, laboratory data on testing for HIV/STIs and STI/HIV testing uptake reported in annual surveys were analysed. Results: The sentinel surveillance network showed no increase in the overall extent of HIV testing and no difference in the proportion of MSM reporting regular annual HIV testing during the campaign (43%) and post campaign (41%). The annual behavioural surveys showed that between 2004 and 2006 there was no significant increase in this overall proportion of MSM reporting having an HIV test in the last 12 months (p = 0.96). The behavioural surveys also showed an increasing trend in the proportion reporting specific STI tests over time: anal swab (26% to 39%, p⩽0.01) and urine test (42% to 50%, p⩽0.01) and there was a steady increase in the amount of STI testing at the clinics detected through the laboratory reports: chlamydia (average increment of 6.4 tests per month, p<0.01), gonorrhoea (6.5 tests per month, p⩽0.01) and syphilis (4.0 tests per month, p⩽0.01) but it began at least 2 years before the campaign and was not accelerated during the campaign. Conclusion: Based on a range of indicators there was no evidence that the campaign increased HIV/STI testing. These findings highlight the importance of evaluating public health campaigns to assess their impact to ensure that they are modified if no impact is identified. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prevalences and correlates of non-viral injecting-related injuries and diseases (IRIDs) in Australian injecting drug users (IDUs) remain unknown. Methods: A cross-sectional survey of IDUs was conducted in six sites across Australia''s eastern states to investigate IRID experience among Australian IDU. Correlates of IRIDs were explored using logistic and negative binomial regression analyses. Results: 393 IDUs were recruited. Lifetime experience of non-serious IRIDs was common (e.g., ‘dirty hit’ 68%); potentially serious and serious IRIDs were less commonly experienced (e.g., abscess 16%; gangrene <1%). Factors independently associated with potentially serious or serious IRIDs in the previous 12 months were: injecting in sites other than arms (Adjusted Odds Ratio 3.0, 95% confidence interval 1.7–5.4), injecting non-powder drug forms (5.0, 2.2–11.2), unstable accommodation (2.0, 1.1–3.5), being aged 25 years or older (4.3, 1.7–10.6) and not always washing hands before injection (9.3, 2.1–41.8). Factors independently associated with multiple IRIDs in the preceding 12 months were using three or more injecting sites (Adjusted Incidence Rate Ratio 1.5, 95% CI 1.1–2.0), injecting in sites other than arms (1.7, 1.3–2.2), using non-powder drug forms (1.9, 1.4–2.5), injecting daily or more often (1.7, 1.3–2.2), current pharmacotherapy experience (1.5, 1.1–1.9), and not always washing hands before injecting (1.9, 1.2–2.9). Discussion: Some IRIDs are widespread among Australian IDUs. Observed associations, particularly the protective effect of handwashing, have useful public health implications. [Copyright &y& Elsevier]

The article offers information on Australia's policy responding to control tobacco use to have contributed to daily smoking prevalence among adults. Topics include smoking prevalence in key populations, including bisexual and other men who have sex with men (GBM) and people living with human immunodeficiency virus, and smoking participation among younger Australian GBM and describe factors associated with smoking.

Accurate incidence estimates are essential for quantifying hepatitis C virus ( HCV) epidemic dynamics and monitoring the effectiveness of public health programmes, as well as for predicting future burden of disease and planning patient care. In Egypt, the country with the largest HCV epidemic worldwide, two modelling studies have estimated age-specific incidence rates that, applied to the age pyramid, would correspond to more than 500 000 Egyptians getting infected annually. This is in contrast to figures of the Egyptian Ministry of Health and Population that estimates new infections to be approximately 100 000 per year. We performed new analyses of nationwide data to examine the modelling assumptions that led to these estimates. Thus, we found that the key assumption of these models of a stationary epidemic is invalid. We propose an alternate approach to estimating incidence based on analysing cohort data; we find that the number of annual new infections is <150 000. [ABSTRACT FROM AUTHOR]

Background: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment.Methods: Consenting patients with HCV infection attending 13 PHCS in Australia or New Zealand are randomized to receive DAA treatment at the local tertiary institution (standard care arm), or their PHCS (intervention arm). The primary endpoint is the proportion commenced on DAAs and cured. Treatment providers at the PHCS include: hepatology nurses, primary care practitioners, or, in two sites, a specialist physician. All PHCS offer opioid substitution therapy.Discussion: The Prime Study is the first real-world, randomized, model of care study exploring the impact of community provision of DAA therapy on HCV-treatment uptake and cure. Although the study has faced challenges unique to this period of time characterized by changing treatment and service delivery, the data gained will be of critical importance in shaping health service policy that enables the elimination of HCV.Trial Registration: ClinicalTrials.gov , ID: NCT02555475 . Registered on 15 September 2015. [ABSTRACT FROM AUTHOR]