Pathways to ensure universal and affordable access to hepatitis C treatment

Direct-acting antivirals (DAAs) have dramatically changed the landscape of hepatitis C treatment and prevention. The World Health Organization has called for the elimination of hepatitis C as a public health threat by 2030. However, the discrepancy in DAA prices across low-, middle- and high-income countries is considerable, ranging from less than US$100 to approximately US$ 40,000 per course, thus representing a major barrier for the scale-up of treatment and elimination. This article describes DAA pricing and pathways to accessing affordable treatment, providing case studies from Australia, Egypt and Portugal. Pathways to accessing DAAs include developing comprehensive viral hepatitis plans to facilitate price negotiations, voluntary and compulsory licenses, patent opposition, joint procurement, and personal importation schemes. While multiple factors influence the price of DAAs, a key driver is a country's capacity and willingness to negotiate with pharmaceutical companies. If negotiations do not lead to a reasonable price, governments have the option to utilise flexibilities outlined in the Agreement on Trade-Related Aspects of Intellectual Property Rights. Affordable access to DAAs is underpinned by collaboration between government, civil society, global organisations and pharmaceutical companies to ensure that all patients can access treatment. Promoting these pathways is critical for influencing policy, improving access to affordable DAAs and achieving hepatitis C elimination

A platform in the use of medicines to treat chronic hepatitis C (PLATINUM C): Protocol for a prospective treatment registry of real-world outcomes for hepatitis C

© 2020, The Author(s). Background: Safe, highly curative, short course, direct acting antiviral (DAA) therapies are now available to treat chronic hepatitis C. DAA therapy is freely available to all adults chronically infected with the hepatitis C virus (HCV) in Australia. If left untreated, hepatitis C may lead to progressive hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Australia is committed to eliminating hepatitis as a public health threat by 2030 set by the World Health Organization. However, since the introduction of funded DAA treatment, uptake has been suboptimal. Australia needs improved strategies for testing, treatment uptake and treatment completion to address the persisting hepatitis C public health problem. PLATINUM C is a HCV treatment registry and research platform for assessing the comparative effectiveness of alternative interventions for achieving virological cure. Methods: PLATINUM C will prospectively enrol people with active HCV infection confirmed by recent detection of HCV ribonucleic acid (RNA) in blood. Those enrolled will agree to allow standardised collection of demographic, lifestyle, treatment, virological outcome and other relevant clinical data to better inform the future management of HCV infection. The primary outcome is virological cure evidenced by sustained virological response (SVR), which is defined as a negative HCV PCR result 6 to 18 months after initial prescription of DAA therapy and no less than 12 weeks after the completion of treatment. Study participants will be invited to opt-in to medication adherence monitoring and quality of life assessments using validated self-reported instruments (EQ-5D-5L). Discussion: PLATINUM C is a treatment registry and platform for nesting pragmatic trials. Data collected will inform the design, development and implementation of pragmatic trials. The digital infrastructure, study procedures and governing systems established by the registry will allow PLATINUM C to support a wider research platform in the management of hepatitis C in primary care. Trial registration: The trial is registered with the Australia and New Zealand Clinical Trials Register (ACTRN12619000023156). Date of registration: 10/01/2019

Global hepatitis C elimination: an investment framework

WHO has set global targets for the elimination of hepatitis B and hepatitis C as a public health threat by 2030. However, investment in elimination programmes remains low. To help drive political commitment and catalyse domestic and international financing, we have developed a global investment framework for the elimination of hepatitis B and hepatitis C. The global investment framework presented in this Health Policy paper outlines national and international activities that will enable reductions in hepatitis C incidence and mortality, and identifies potential sources of funding and tools to help countries build the economic case for investing in national elimination activities. The goal of this framework is to provide a way for countries, particularly those with minimal resources, to gain the substantial economic benefit and cost savings that come from investing in hepatitis C elimination

Staying hepatitis C negative: a systematic review and meta-analysis of cure and reinfection in people who inject drugs

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND AND AIMS: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in people who inject drugs (PWID). METHODS: A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models. RESULTS: The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76). CONCLUSIONS: Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.National Health and Medical Research Council of Australi

Innovative strategies for the elimination of viral hepatitis at a national level: a country case series

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints

High Rates of Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection in People Who Inject Drugs: A Prospective Cohort Study

Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterisedcohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possiblereinfections were identified (confirmed reinfections were those genetically distinct from the previous infection andpossible reinfections were used to define instances where genetic differences between infections could not beassessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfectionwas 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that ofprimary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]:2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93,95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting.In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recentinjecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmedreinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03,p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection.Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneouslyclear.Conclusions: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at highrates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks ofhepatitis C reinfection are required

Understanding HIV risk and addressing barriers to testing for men who have sex with men in Australia

Diagnoses of HIV among men who have sex with men (MSM) are increasing in many developed countries. In Australia, rising rates of HIV diagnoses among MSM have been attributed to increasing prevalence of unprotected anal intercourse, dramatic increases in the prevalence of other STIs including syphilis, gonorrhoea and chlamydia, and (following the introduction of ART) an expanding pool of healthy, sexually active, HIV positive MSM. Surveillance data also suggest a shift in the epidemiology of HIV within Australian MSM populations in recent years, with an increasing proportion of younger MSM being diagnosed with HIV and other STIs. Although identified in other developed countries as a key factor likely to be associated with increasing HIV transmission among MSM, local data on undiagnosed HIV (HIV positive individuals who are unaware of their HIV infection) in Australia is limited. Additional information regarding the prevalence and correlates of undiagnosed HIV among MSM is required to understand how undiagnosed infection may impact on transmission rates. In addition to initiatives to maintain and enhance awareness of risk and protective behaviours for HIV and other STIs, encouraging regular HIV and other STI testing among MSM is a central part of Australia’s HIV prevention response. Increasing the frequency of HIV and other STI testing among high risk MSM is considered particularly important to detect primary infections and undiagnosed infections. The benefits of testing are several. First, it provides an opportunity for the provision of education and counselling, regardless of the outcome of the test. Second, for those found to have infection, it represents a pathway into HIV care and treatment. Finally, the reduction in viral load that can be achieved through treatment can substantially lower the risk of transmission to sexual partners. Annual self-reported HIV testing rates among MSM in Australia are consistently high (60%-68%). Nevertheless, recent clinic data suggest that the proportion of MSM undergoing more frequent testing is falling well short of the 3-6 monthly recommendation for high-risk men, and a significant proportion with HIV infection may be undiagnosed or diagnosed late. Numerous barriers to frequent testing among MSM have been identified previously including low risk perception, difficulties getting an appointment, the requirement for multiple clinic appointments for specimen collection and for receiving results, and difficulties in finding a ‘gay-friendly’ doctor. This thesis provides estimates of the extent of undiagnosed HIV infection in MSM and then describes evaluations of the impact of a range of preventative approaches to increasing HIV and STI testing for MSM in Australia. Limitations of current HIV epidemiological approaches in Australia and the potential impact of undiagnosed infections (and, in turn, the importance of frequent HIV testing) on HIV epidemiology were highlighted in the ‘Suck it and See’ Study. Field-based HIV testing techniques used for the first time in Australia enabled measurement of the biological prevalence of HIV alongside behavioural data, revealing an undiagnosed HIV prevalence estimate of 31%, and confirmed the previously unrecognised impact of undiagnosed HIV on transmissions. These outcomes, combined with the known limitations of self-report measures for estimating HIV prevalence, as currently used in Australia, makes a strong case for the incorporation of biological measures into routine HIV and behavioural surveillance in Australia. A quantitative and qualitative evaluation of a national STI awareness campaign demonstrated the effectiveness of social marketing campaigns in encouraging HIV/STI testing. The campaign aimed to increase HIV and STI testing among MSM by improving awareness and knowledge of the importance of regular testing. The quantitative evaluation demonstrated the impact of the campaign on awareness and health-seeking behaviour. These findings were complemented by those of the qualitative evaluation, which identified key elements of campaign style, language and broadcast schedule, in particular the use of mainstream media channels that contributed to impact, reach, acceptability and engagement. The qualitative evaluation also identified campaign limitations, including its limited ability to reduce risk behaviour and encourage community dialogue or interpersonal communication. The lack of portrayal of negative consequences associated with not getting tested and the limited engagement with the campaign content were identified as a potential reason for these limitations. Web-based interventions offer a new and potentially more engaging approach to health promotion than traditional types of social marketing. In particular, newer Web 2.0 applications like social networking sites have interactive functions and rapidly increasing popularity, characteristic that can be exploited to provide a unique platform to deliver health promotion messages. “Queer as F**K” is an innovative sexual health program delivered to gay men via social networking sites. The evaluation of its pilot provided evidence of the feasibility and acceptability of health promotion delivered through social networking sites and other new media for reaching and engaging gay men in sexual health discussions. Increasing avenues to deliver sexual health promotion and helping to normalise sexual health discussions among MSM are important steps to help reduce stigma and other structural/societal barriers to testing. These new technologies can support or accompany existing mass media campaigns that have been shown to be effective at encouraging testing. Despite successful and innovative marketing approaches designed to enhance HIV and other STI testing among MSM, structural barriers to testing remain. Men currently need a second appointment to receive their test results, as conventional HIV serology results are not available for two or more days. Thus, for high-risk men, each HIV test could be associated with two visits to a clinic, meaning up to eight clinic visits per year for HIV testing alone. Rapid HIV testing could enable men to increase their testing frequency by halving the number of visits required In Australia, HIV testing is only available through clinical settings and until 2011 HIV rapid testing was not supported through the Australian National HIV Testing Policy. To inform changes to HIV testing policy and practice in Australia, and demonstrate the benefit of alternative testing models, a systematic review of community-based models of testing for MSM, with a focus on rapid testing was undertaken. The review provides evidence that community models attract a significant proportion of high-risk MSM and reach a high proportion of men who have never tested before, supporting the diversification of testing strategies in Australia to increase HIV testing rates among MSM. In summary, while improving access to HIV testing for MSM in Australia is recognised as key to reducing new diagnoses and onward transmission, achieving this outcome requires complementary and supporting strategies, including biomedical, behavioural and structural interventions. As these new strategies are implemented, it is imperative that effective and ongoing evaluations measure the impact of the overall strategy and identify the most effective components. This information in turn informs the ongoing refinement of the prevention strategies that will ultimately help reduce the number of HIV infections among MSM and the burden on the health system and the community. This thesis contributes greatly to our understanding of the impact of undiagnosed HIV in driving the HIV epidemic among MSM in Australia. It provides strong evidence for the need to diversify testing strategies in Australia to reduce the prevalence of undiagnosed HIV, including the introduction of rapid HIV testing into both clinical and community based settings. Findings presented in this thesis suggest that the introduction of new testing strategies need to be accompanied by engaging sexual health promotion interventions that encourage and increase the uptake and frequency of HIV testing among MSM populations

Understanding HIV risk and addressing barriers to testing for men who have sex with men in Australia

Diagnoses of HIV among men who have sex with men (MSM) are increasing in many developed countries. In Australia, rising rates of HIV diagnoses among MSM have been attributed to increasing prevalence of unprotected anal intercourse, dramatic increases in the prevalence of other STIs including syphilis, gonorrhoea and chlamydia, and (following the introduction of ART) an expanding pool of healthy, sexually active, HIV positive MSM. Surveillance data also suggest a shift in the epidemiology of HIV within Australian MSM populations in recent years, with an increasing proportion of younger MSM being diagnosed with HIV and other STIs. Although identified in other developed countries as a key factor likely to be associated with increasing HIV transmission among MSM, local data on undiagnosed HIV (HIV positive individuals who are unaware of their HIV infection) in Australia is limited. Additional information regarding the prevalence and correlates of undiagnosed HIV among MSM is required to understand how undiagnosed infection may impact on transmission rates. In addition to initiatives to maintain and enhance awareness of risk and protective behaviours for HIV and other STIs, encouraging regular HIV and other STI testing among MSM is a central part of Australia’s HIV prevention response. Increasing the frequency of HIV and other STI testing among high risk MSM is considered particularly important to detect primary infections and undiagnosed infections. The benefits of testing are several. First, it provides an opportunity for the provision of education and counselling, regardless of the outcome of the test. Second, for those found to have infection, it represents a pathway into HIV care and treatment. Finally, the reduction in viral load that can be achieved through treatment can substantially lower the risk of transmission to sexual partners. Annual self-reported HIV testing rates among MSM in Australia are consistently high (60%-68%). Nevertheless, recent clinic data suggest that the proportion of MSM undergoing more frequent testing is falling well short of the 3-6 monthly recommendation for high-risk men, and a significant proportion with HIV infection may be undiagnosed or diagnosed late. Numerous barriers to frequent testing among MSM have been identified previously including low risk perception, difficulties getting an appointment, the requirement for multiple clinic appointments for specimen collection and for receiving results, and difficulties in finding a ‘gay-friendly’ doctor. This thesis provides estimates of the extent of undiagnosed HIV infection in MSM and then describes evaluations of the impact of a range of preventative approaches to increasing HIV and STI testing for MSM in Australia. Limitations of current HIV epidemiological approaches in Australia and the potential impact of undiagnosed infections (and, in turn, the importance of frequent HIV testing) on HIV epidemiology were highlighted in the ‘Suck it and See’ Study. Field-based HIV testing techniques used for the first time in Australia enabled measurement of the biological prevalence of HIV alongside behavioural data, revealing an undiagnosed HIV prevalence estimate of 31%, and confirmed the previously unrecognised impact of undiagnosed HIV on transmissions. These outcomes, combined with the known limitations of self-report measures for estimating HIV prevalence, as currently used in Australia, makes a strong case for the incorporation of biological measures into routine HIV and behavioural surveillance in Australia. A quantitative and qualitative evaluation of a national STI awareness campaign demonstrated the effectiveness of social marketing campaigns in encouraging HIV/STI testing. The campaign aimed to increase HIV and STI testing among MSM by improving awareness and knowledge of the importance of regular testing. The quantitative evaluation demonstrated the impact of the campaign on awareness and health-seeking behaviour. These findings were complemented by those of the qualitative evaluation, which identified key elements of campaign style, language and broadcast schedule, in particular the use of mainstream media channels that contributed to impact, reach, acceptability and engagement. The qualitative evaluation also identified campaign limitations, including its limited ability to reduce risk behaviour and encourage community dialogue or interpersonal communication. The lack of portrayal of negative consequences associated with not getting tested and the limited engagement with the campaign content were identified as a potential reason for these limitations. Web-based interventions offer a new and potentially more engaging approach to health promotion than traditional types of social marketing. In particular, newer Web 2.0 applications like social networking sites have interactive functions and rapidly increasing popularity, characteristic that can be exploited to provide a unique platform to deliver health promotion messages. “Queer as F**K” is an innovative sexual health program delivered to gay men via social networking sites. The evaluation of its pilot provided evidence of the feasibility and acceptability of health promotion delivered through social networking sites and other new media for reaching and engaging gay men in sexual health discussions. Increasing avenues to deliver sexual health promotion and helping to normalise sexual health discussions among MSM are important steps to help reduce stigma and other structural/societal barriers to testing. These new technologies can support or accompany existing mass media campaigns that have been shown to be effective at encouraging testing. Despite successful and innovative marketing approaches designed to enhance HIV and other STI testing among MSM, structural barriers to testing remain. Men currently need a second appointment to receive their test results, as conventional HIV serology results are not available for two or more days. Thus, for high-risk men, each HIV test could be associated with two visits to a clinic, meaning up to eight clinic visits per year for HIV testing alone. Rapid HIV testing could enable men to increase their testing frequency by halving the number of visits required In Australia, HIV testing is only available through clinical settings and until 2011 HIV rapid testing was not supported through the Australian National HIV Testing Policy. To inform changes to HIV testing policy and practice in Australia, and demonstrate the benefit of alternative testing models, a systematic review of community-based models of testing for MSM, with a focus on rapid testing was undertaken. The review provides evidence that community models attract a significant proportion of high-risk MSM and reach a high proportion of men who have never tested before, supporting the diversification of testing strategies in Australia to increase HIV testing rates among MSM. In summary, while improving access to HIV testing for MSM in Australia is recognised as key to reducing new diagnoses and onward transmission, achieving this outcome requires complementary and supporting strategies, including biomedical, behavioural and structural interventions. As these new strategies are implemented, it is imperative that effective and ongoing evaluations measure the impact of the overall strategy and identify the most effective components. This information in turn informs the ongoing refinement of the prevention strategies that will ultimately help reduce the number of HIV infections among MSM and the burden on the health system and the community. This thesis contributes greatly to our understanding of the impact of undiagnosed HIV in driving the HIV epidemic among MSM in Australia. It provides strong evidence for the need to diversify testing strategies in Australia to reduce the prevalence of undiagnosed HIV, including the introduction of rapid HIV testing into both clinical and community based settings. Findings presented in this thesis suggest that the introduction of new testing strategies need to be accompanied by engaging sexual health promotion interventions that encourage and increase the uptake and frequency of HIV testing among MSM populations