Infectious Diseases - Research Publications

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    Evolutionary study and phylodynamic pattern of human influenza A/H3N2 virus in Indonesia from 2008 to 2010.
    Agustiningsih, A ; Trimarsanto, H ; Restuadi, R ; Artika, IM ; Hellard, M ; Muljono, DH ; Chiang, T-Y (Public Library of Science (PLoS), 2018)
    Influenza viruses are by nature unstable with high levels of mutations. The sequential accumulation of mutations in the surface glycoproteins allows the virus to evade the neutralizing antibodies. The consideration of the tropics as the influenza reservoir where viral genetic and antigenic diversity are continually generated and reintroduced into temperate countries makes the study of influenza virus evolution in Indonesia essential. A total of 100 complete coding sequences (CDS) of Hemagglutinin (HA) and Neuraminidase (NA) genes of H3N2 virus were obtained from archived samples of Influenza-Like Illness (ILI) surveillance collected from 2008 to 2010. Our evolutionary and phylogenetic analyses provide insight into the dynamic changes of Indonesian H3N2 virus from 2008 to 2010. Obvious antigenic drift with typical 'ladder-like' phylogeny was observed with multiple lineages found in each year, suggesting co-circulation of H3N2 strains at different time periods. The mutational pattern of the Indonesian H3N2 virus was not geographically related as relatively low levels of mutations with similar pattern of relative genetic diversity were observed in various geographical origins. This study reaffirms that the existence of a particular lineage is most likely the result of adaptation or competitive exclusion among different host populations and combination of stochastic ecological factors, rather than its geographical origin alone.
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    Trial and error: evaluating and refining a community model of HIV testing in Australia.
    Ryan, KE ; Pedrana, A ; Leitinger, D ; Wilkinson, AL ; Locke, P ; Hellard, ME ; Stoové, M (Springer Science and Business Media LLC, 2017-10-10)
    BACKGROUND: The 2012 regulatory approval of HIV rapid point of care (RPOC) tests in Australia and a national strategic focus on HIV testing provided a catalyst for implementation of non-clinical HIV testing service models. PRONTO! opened in 2013 as a two-year trial delivering peer-led community-based HIV RPOC tests targeting gay, bisexual and other men who have sex with men (GBM), with the aim of increasing HIV testing frequency. Initial data suggested this aim was not achieved and, as part of a broader service evaluation, we sought to explore client acceptability and barriers to testing at PRONTO! to refine the service model. METHODS: We present descriptive and thematic analyses of data from two in-depth evaluation surveys and four focus groups with PRONTO! clients focused on service acceptability, client testing history, intentions to test and barriers to testing for HIV and other sexually transmitted infections (STIs). RESULTS: The three novel aspects of the PRONTO! model, testing environment, rapid-testing, peer-staff, were reported to be highly acceptable among survey and focus group participants. Focus group discussions revealed that the PRONTO! model reduced anxiety associated with HIV testing and created a comfortable environment conducive to discussing sexual risk and health. However, an absence of STI testing at PRONTO!, driven by restrictions on medical subsidies for STI testing and limited funds available at the service level created a barrier to HIV testing. An overwhelming majority of PRONTO! clients reported usually testing for STIs alongside HIV and most reported plans to seek STI testing after testing for HIV at PRONTO!. When deciding where, when and what to test for, clients reported balancing convenience and relative risk and consequences for each infection as guiding their decision-making. CONCLUSIONS: A community-based and peer-led HIV testing model reduced previously reported barriers to HIV testing, while introducing new barriers. The absence of STI testing at PRONTO! and the need to access multiple services for comprehensive sexual health screening, created a significant service engagement barrier for some clients. Understanding client motivations to access testing and ensuring novel service models meet client needs is crucial for developing acceptable sexual health services for high-risk populations.
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    WHO guidelines on testing for hepatitis B and C - meeting targets for testing.
    Hellard, ME ; Chou, R ; Easterbrook, P (Springer Science and Business Media LLC, 2017-11-01)
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    Methodological challenges in appraising evidence on diagnostic testing for WHO guidelines on hepatitis B and hepatitis C virus infection.
    Chou, R ; Easterbrook, P ; Hellard, M (Springer Science and Business Media LLC, 2017-11-01)
    Linking persons with hepatitis B (HBV) and hepatitis C (HCV) infection with appropriate prevention and treatment requires that they first be diagnosed. The World Health Organization (WHO) has developed its first guidelines on testing for chronic HBV and HCV infection, using a framework based on methods from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group for the formulation of recommendations, including determining the strength of recommendations and quality of evidence. Recommendations were formulated based on the overall quality of the evidence, in addition to other considerations, including the balance between benefits and harms, values and preferences, feasibility and resource implications. This article summarizes methodological challenges and additional considerations encountered in applying these procedures to diagnostic testing for viral hepatitis, and strategies to address these. Direct evidence on the effects of tests and test strategies on clinical outcomes was not available. Given the availability of effective treatments for HBV and HCV that are generally acceptable to patients, the Guidelines Development Group (GDG) considered diagnostic accuracy a reasonable surrogate for clinical outcomes. In order to increase the number of patients identified with chronic HBV and HCV infection who could benefit from treatments, the GDG determined that tests and testing strategies associated with slightly lower diagnostic accuracy could be recommended when associated with lower costs; increased testing access, uptake, and linkage to care; greater feasibility; or if preferred by patients.
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    Undiagnosed HIV infections among gay and bisexual men increasingly contribute to new infections in Australia.
    Gray, RT ; Wilson, DP ; Guy, RJ ; Stoové, M ; Hellard, ME ; Prestage, GP ; Lea, T ; de Wit, J ; Holt, M (Wiley, 2018-04)
    INTRODUCTION: We determined the contribution of undiagnosed HIV to new infections among gay and bisexual men (GBM) over a 12-year period in Australia where there has been increasing focus on improving testing and HIV treatment coverage. METHODS: We generated annual estimates for each step of the HIV cascade and the number of new HIV infections for GBM in Australia over 2004 to 2015 using relevant national data. Using Bayesian melding we then fitted a quantitative model to the cascade and incidence estimates to infer relative transmission coefficients associated with being undiagnosed, diagnosed and not on ART, on ART with unsuppressed virus, or on ART with suppressed virus. RESULTS: Between 2004 and 2015, we estimated the percentage of GBM with HIV in Australia who were unaware of their status to have decreased from 14.5% to 7.5%. During the same period, there was a substantial increase in the number and proportion of GBM living with HIV on treatment and with suppressed virus, with the number of virally suppressed GBM increasing from around 3900 (30.2% of all GBM living with HIV) in 2004 to around 14,000 (73.7% of all GBM living with HIV) in 2015. Despite the increase in viral suppression, the annual number of new infections rose from around 660 to around 760 over this period. Our results have a wide range due to the uncertainty in the cascade estimates and transmission coefficients. Nevertheless, undiagnosed GBM increasingly appear to contribute to new infections. The proportion of new infections attributable to undiagnosed GBM almost doubled from 33% in 2004 to 59% in 2015. Only a small proportion (<7%) originated from GBM with suppressed virus. DISCUSSION: Our study suggests that an increase in HIV treatment coverage in Australia has reduced the overall risk of HIV transmission from people living with HIV. However, the proportion of infections and the rate of transmission from undiagnosed GBM has increased substantially. These findings highlight the importance of HIV testing and intensified prevention for Australian GBM at high risk of HIV.
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    A latent class approach to identify multi-risk profiles associated with phylogenetic clustering of recent hepatitis C virus infection in Australia and New Zealand from 2004 to 2015.
    Bartlett, SR ; Applegate, TL ; Jacka, BP ; Martinello, M ; Lamoury, FM ; Danta, M ; Bradshaw, D ; Shaw, D ; Lloyd, AR ; Hellard, M ; Dore, GJ ; Matthews, GV ; Grebely, J (Wiley, 2019-02)
    INTRODUCTION: Over the last two decades, the incidence of hepatitis C virus (HCV) co-infection among men who have sex with men (MSM) living with HIV began increasing in post-industrialized countries. Little is known about transmission of acute or recent HCV, in particular among MSM living with HIV co-infection, which creates uncertainty about potential for reinfection after HCV treatment. Using phylogenetic methods, clinical, epidemiological and molecular data can be combined to better understand transmission patterns. These insights may help identify strategies to reduce reinfection risk, enhancing effectiveness of HCV treatment as prevention strategies. The aim of this study was to identify multi-risk profiles and factors associated with phylogenetic pairs and clusters among people with recent HCV infection. METHODS: Data and specimens from five studies of recent HCV in Australia and New Zealand (2004 to 2015) were used. HCV Core-E2 sequences were used to infer maximum likelihood trees. Clusters were identified using 90% bootstrap and 5% genetic distance threshold. Multivariate logistic regression and latent class analyses were performed. RESULTS: Among 237 participants with Core-E2 sequences, 47% were in a pair/cluster. Among HIV/HCV co-infected participants, 60% (74/123) were in a pair/cluster, compared to 30% (34/114) with HCV mono-infection (p < 0.001). HIV/HCV co-infection (vs. HCV mono-infection; adjusted odds ratio (AOR), 2.37, 95% confidence interval (CI), 1.45, 5.15) was independently associated with phylogenetic clustering. Latent class analysis identified three distinct risk profiles: (1) people who inject drugs, (2) HIV-positive gay and bisexual men (GBM) with low probability of injecting drug use (IDU) and (3) GBM with IDU & sexual risk behaviour. Class 2 (vs. Class 1, AOR 3.40; 95% CI, 1.52, 7.60), was independently associated with phylogenetic clustering. Many clusters displayed homogeneous characteristics, such as containing individuals exclusively from one city, individuals all with HIV/HCV co-infection or individuals sharing the same route of acquisition of HCV. CONCLUSIONS: Clusters containing individuals with specific characteristics suggest that HCV transmission occurs through discrete networks, particularly among HIV/HCV co-infected individuals. The greater proportion of clustering found among HIV/HCV co-infected participants highlights the need to provide broad direct-acting antiviral access encouraging rapid uptake in this population and ongoing monitoring of the phylogeny.
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    HIV diagnoses in migrant populations in Australia-A changing epidemiology.
    Gunaratnam, P ; Heywood, AE ; McGregor, S ; Jamil, MS ; McManus, H ; Mao, L ; Lobo, R ; Brown, G ; Hellard, M ; Marukutira, T ; Bretaña, NA ; Lang, C ; Medland, N ; Bavinton, B ; Grulich, A ; Guy, R ; Khudyakov, YE (Public Library of Science (PLoS), 2019)
    INTRODUCTION: We conducted a detailed analysis of trends in new HIV diagnoses in Australia by country of birth, to understand any changes in epidemiology, relationship to migration patterns and implications for public health programs. METHODS: Poisson regression analyses were performed, comparing the age-standardised HIV diagnosis rates per 100,000 estimated resident population between 2006-2010 and 2011-2015 by region of birth, with stratification by exposure (male-to-male sex, heterosexual sex-males and females). Correlation between the number of permanent and long-term arrivals was also explored using linear regression models. RESULTS: Between 2006 and 2015, there were 6,741 new HIV diagnoses attributed to male-to-male sex and 2,093 attributed to heterosexual sex, with the proportion of diagnoses attributed to male-to-male sex who were Australian-born decreasing from 72.5% to 66.5%. Compared with 2006-2010, the average annual HIV diagnosis rate per 100,000 in 2011-15 attributed to male-to-male sex was significantly higher in men born in South-East Asia (summary rate ratio (SRR) = 1.37, p = 0.001), North-East Asia (SRR = 2.18, p<0.001) and the Americas (SRR = 1.37, p = 0.025), but significantly lower as a result of heterosexual sex in men born in South-East Asia (SRR = 0.49, p = 0.002), Southern and Central Asia (SRR = 0.50, p = 0.014) and Sub-Saharan Africa (SRR = 0.39, p<0.001) and women born in South-East Asia (SRR = 0.61, p = 0.002) and Sub-Saharan Africa (SRR = 0.61, p<0.001). Positive associations were observed between the number of permanent and long-term arrivals and HIV diagnoses particularly in relation to diagnoses associated with male-to-male sex in men from North Africa and the Middle East, North Asia, Southern and Central Asia and the Americas. CONCLUSION: The epidemiology of HIV in Australia is changing, with an increase in HIV diagnosis rates attributed to male-to-male sex amongst men born in Asia and the Americas. Tailored strategies must be developed to increase access to, and uptake of, prevention, testing and treatment in this group.
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    Assessment of service refinement and its impact on repeat HIV testing by client's access to Australia's universal healthcare system: a retrospective cohort study.
    Ryan, KE ; Wilkinson, AL ; Asselin, J ; Leitinger, DP ; Locke, P ; Pedrana, A ; Hellard, M ; Stoové, M (Wiley, 2019-08)
    INTRODUCTION: Achieving the virtual elimination of HIV requires equitable access to HIV prevention tools for all priority populations. Restricted access to healthcare means migrants face particular barriers to HIV prevention services. In February 2016, a peer-led rapid HIV testing service for gay, bisexual and other men who have sex with men (gay and bisexual men, GBM) in Melbourne, Australia, introduced free sexually transmissible infection (STI) testing funded through Medicare (Australia's universal healthcare system). Medicare ineligible migrant clients were required to pay up to $158AUD for STI tests. We determined the uptake of STI testing and assessed the impact on repeat HIV testing among Medicare eligible and ineligible clients. METHODS: All HIV tests conducted between August 2014 and March 2018 were included. We describe client characteristics, STI testing uptake and HIV/STI positivity among Medicare eligible and ineligible clients. Repeat HIV testing, assessed as the percentage of HIV tests with a return test within six months, was compared pre-integration (August 2014-June 2016) and post-integration(July 2016-March 2018) of STI testing using segmented linear regression of monthly aggregate data for Medicare eligible and ineligible clients. RESULTS: Analyses included 9134 HIV tests among 4753 individuals. Medicare ineligible clients were younger (p < 0.01), and fewer reported previously testing for HIV (p < 0.01) and high HIV risk sexual behaviours. There was no difference in HIV positivity between the two groups (p = 0.09). STI testing uptake was significantly lower among Medicare ineligible clients (7.6%, 85.3%; p < 0.01). Following STI testing introduction there was an immediate increase in six-month return HIV testing (6.4%; p = 0.02) and a significantly increasing rate of return HIV testing between July 2016 and March 2018 (0.5% per month; p < 0.01) among Medicare eligible clients but no immediate change in return testing (-0.9%; p = 0.7) or the rate of change in return testing between July 2016 and March 2018 (0.1% per month; p = 0.3) among Medicare ineligible clients. In March 2018, six-month return HIV testing was 52.3% and 13.2% among Medicare eligible and ineligible clients respectively. DISCUSSION: Improvements in return HIV testing observed among Medicare eligible clients did not extend to Medicare ineligible clients highlighting the impact of inequitable access to comprehensive sexual healthcare on test-and-treat approaches to HIV prevention.
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    Program and Abstracts from the Canadian Digestive Diseases Week™ 2016.
    Gastroenterology, CAO ; For The Study Of The Liver, CA (Hindawi Limited, 2016)
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    Hepatitis C risk perceptions and attitudes towards reinfection among HIV-diagnosed gay and bisexual men in Melbourne, Australia.
    Schroeder, SE ; Higgs, P ; Winter, R ; Brown, G ; Pedrana, A ; Hellard, M ; Doyle, J ; Stoové, M (Wiley, 2019-05)
    INTRODUCTION: Gay and bisexual men (GBM) are at increased risk of hepatitis C/HIV co-infection. In Australia, the availability of subsidized direct-acting antiviral treatment for hepatitis C has rendered eliminating co-infection possible. High reinfection rates in subgroups with continued exposure may compromise elimination efforts. To inform the development of hepatitis C risk reduction support in GBM, we explored reinfection risk perceptions and attitudes among GBM living with HIV recently cured from hepatitis C. METHODS: Between April and August 2017, 15 GBM living with diagnosed HIV were recruited from high caseload HIV primary care services in Melbourne following successful hepatitis C treatment. In-depth interviews were conducted exploring understandings of hepatitis C risks, experiences of co-infection and attitudes towards reinfection. Constructivist grounded theory guided data aggregation. RESULTS: Participants' understandings of their hepatitis C infection and reinfection trajectories were captured in three categories. Hepatitis C and HIV disease dichotomies: Hepatitis C diagnosis was a shock to most participants and contrasted with feelings of inevitability associated with HIV seroconversion. While HIV was normalized, hepatitis C was experienced as highly stigmatizing. Despite injecting drug use, interviewees did not identify with populations typically at risk of hepatitis C. Risk environments and avoiding reinfection: Interviewees identified their social and sexual networks as risk-perpetuating environments where drug use was ubiquitous and higher risk sex was common. Avoiding these risk environments to avoid reinfection resulted in community disengagement, leaving many feeling socially isolated. Hepatitis C care as a catalyst for change: Engagement in hepatitis C care contributed to a better understanding of hepatitis C risks. Interviewees were committed to applying their improved competencies around transmission risk reduction to avoid reinfection. Interviewees also considered hepatitis C care as a catalyst to reduce their drug use. CONCLUSIONS: Hepatitis C/HIV co-infection among GBM cannot be understood in isolation from co-occurring drug use and sex, nor as separate from their HIV infection. Hepatitis C prevention must address subcultural heterogeneity and the intersectionality between multiple stigmatized social identities. Hepatitis C care presents an opportunity to provide support beyond cure. Peer support networks could mitigate social capital loss following a commitment to behaviour change and reduce hepatitis C reinfection risks.