Helen Tyrrell, Hepatitis Australia, provided a progress report on the targets from the 2012 Auckland statement on viral hepatitis. Helen Tyrrell described the “national shame”, that 1,000 people will die from hepatitis related liver disease in Australia in 2014. These rates are higher than those at the height of the HIV/AIDS mortality in 1994 in Australia.  Viral hepatitis requires the same action and response which HIV/AIDS mortality rates elicited in order to reverse the “rising death toll from viral hepatitis”.

Target progress:

Target 1: by 2016, halve the incidence of hepatitis C infections by doubling the amount of new injecting equipment distributed in the general community and implementing NSPs in prisons. 

Limited progress has been made in achieving this target thus far. In 2012 the ACT announced a trial of the distribution of sterile injecting equipment in a prison, however the trial has not yet commenced.  Contrary to this target, the 4^th National Hepatitis C Strategy does not include a priority action area which encourages trial needle and syringe programs (NSPs) in prisons. This is a backwards step as this priority action area was included in the previous strategy. Veering off the path of prioritising the need for NSPs in prisons undermines the development of an enabling policy environment to assist with preventing HCV transmission in high HCV prevalence settings.    

Target 2: Apply consistent funding of Hepatitis B vaccines for all those at greatest risk

A national policy commitment to this target is reflected in the 2^nd National Hepatitis B Strategy. Tyrrell highlighted that there has been inequitable access to funded vaccination programs for key populations.

Target 3: Ensure at least 80% of people living with Hepatitis B and C are diagnosed

April 2014 saw the announcement of $4.6 million in funding to increase the uptake of hepatitis B testing and treatment, however the planned distribution of this funding has not been publicised. This target largely related to hepatitis B as estimates suggest that 80% of people living with hepatitis C have been diagnosed.    

Target 4: Ensure 5% of people living with hepatitis C receive anti-viral medication each year

This target is reflected in the 4^th National Hepatitis C Strategy. This target requires accelerated PBAC and Cabinet approval process for new HCV drugs and promotion of new treatment options.

Target 5: Guarantee that 10% of people living with hepatitis B receive antiviral treatment each year

This target is again reflected in the 2^nd National Hepatitis B Strategy target, aiming for 15% of people living with hepatitis B to be on treatment.  

Whilst there has been some progress in the target areas, significant prioritisation of viral hepatitis will be required to meet the targets by 2016. The minimal progress is a call to action for state and federal governments to upscale the response required to both meet targets and reduce numbers of avoidable viral hepatitis related liver deaths. 

In Prof Greg Dore’s exciting presentation on Friday at the 9th Viral Hepatitis Conference, Expanding access to hepatitis C treatment through primary care: Challenges and opportunities, he spoke about the HCV disease burden in Australia and the opportunities for increased involvement of GP prescribing whilst acknowledging some of the current barriers.

Despite an expanding burden of progressive liver disease, treatment numbers remain low at around 1%. Australia needs to increase numbers of people receiving antiviral therapy to around 6% as the numbers of people with cirrhosis are projected to reach over 37,500. Increased efficacy of future treatment alone will not significantly reduce the burden of disease. Greg noted the number of prescribers is a key determinant of treatment uptake.

GPs already manage very complicated patients with multiple chronic diseases, including HIV, and many are involved in addiction medicine. Data from recent studies, such as ETHOS and the ASHM GP Treatment Initiation Pilot, was presented and demonstrated HCV treatment can be provided successfully in primary care settings with efficacy rates comparable to tertiary centres. Greg acknowledged current barriers exist in expanding HCV treatment in primary care, such as the Highly Specialised Drugs regulations, existing HCV treatments are complex (but that these will change soon), that interferon-free direct acting antiviral therapy will likely have initial s100 restrictions and that there is still some conservatism among specialists. The need for primary care incentives was also highlighted.

Greg proposed strategies to increase assessment and treatment uptake which included changes to s100 regulations and antiviral therapy access through public health advocacy; simpler treatment assessment, treatment regimens and delivery; increased education and involvement of health care professionals.

In closing, Greg said it was time to move forward and not to pit one model of care against the other (e.g. GP prescribing vs nurse-led models), as there is a role for multiple models in order to increase the number of prescribers to treat the 10,000-15,000 people that is needed to reduce the burden of HCV in Australia. A person with a fibrosis stage F0 to F2 will not require ongoing monitoring once cured of their HCV, so the burden of HCV disease will decrease as more are treated.

It is exciting times in hepatitis C – what other chronic disease can offer a cure? Let’s work together and get as many treated as we can.

Almost 200 delegates were supported through the Australia Awards Fellowship Program (and a small number of other donors) to attend an ASHM Leadership Course before and after the AIDS2014 Conference.

Participants were also provided with mentoring throughout the Conference and a dedicated mentoring space where they could meet with each other, hold impromptu meetings and hook up with their mentors either individually or in groups.

Most participants attended a short course before the conference as well and some are attending short courses now. They cover a range of topics from HIV Medicine, Community Advocacy, Research and Laboratory skills.

The two days before the conference were quite inspirational and gave participants an opportunity to experience how leaders develop their skills and nurture leadership values within their organisations and communities. The MH17 disaster gave participants an insight into how Leaders tried to make sense of such a thing and also provided an opportunity for immediate and subsequent discussion of this issue.

On Saturday, following the conference participants took learnings from the conference and their short courses and had an opportunity for hands on learning in a range of about 20 skills building workshops which spanned issues such as results based planning and management, through to setting up a face book page, quality improvement, preparing a manuscript for publication, harm reduction, improving abstract writing skills, research skills and techniques and developing a social media presence.

Sunday was the time for reflection and planning. Particularly, planning to make sure that the group develops into a network and continues its networking and mentoring once people return home. A full report will be compiled over the next month and the group will continue to communicate through the ASHM Partnership Platform which facilitates ongoing mentoring.

ASHM and collaborators from AFAO, ARCSHS, Burnet, Kirby, Monash, Sydney University and NRL came together to enhance the participation of these regional delegates.  We did this by negotiating with the Department of Foreign Affairs and Trade to prioritise round 14 of the AAF program to Conference related activities. Delegates were from 20 countries from Asia, Pacific and African regions.

HIV monitoring focuses on plasma RNA viral loads and CD4 T- cell counts from the blood, but this only represents a part of the total infection in other parts of the body such as the gut and genital tract. A better understanding of mucosal immunity at these sites has implications for both prevention (microbicides) and treatment research (immune reconstitution outside of PBMCs).

Laura Romas from the University of Manitoba, Canada presented data on the rectal mucosa from HIV-exposed seronegative (HESN) partners in discordant MSM couples and susceptibility to HIV-1 infection, the first time this has been investigated. She found 25 differentially expressed proteins (of 289 identified) that were overabundant in HESN MSM (p< 0.05), and had functions related to acute phase response, antimicrobial defence and Ig-mediated immunity. These proteins did not show a significant correlation (p>0.05) with clinical variables (frequency oral/anal sex, HIV-neutralizing IgA, and viral load of HIV+ partner). One in particular, Antiprotease 1 (AP1) reduced HIV infection by 50% in PBMC culture at physiologically relevant concentrations. Planned further research will aim to elucidate if increased AP1 expression is as a result of HIV-exposure or genetic variability. This could have very interesting implications for MSM prevention strategies and microbicide development.

The GI tract is know as an early site of viral replication and associated immunopathogenesis. Whilst ART stimulates CD4 T – cell recovery in blood, its effects on the GI tract are much less pronounced. However, as earlier initiation of ART seems to preserve more peripheral CD4 T – cells, Claire Deleage from the USA investigated the effect of early ART initiation on the GI tract (lamina propria CD4 T-cells) with a small cohort of Thai patients treated during Fiebig stage 1/2 or 3+ versus chronic controls. Unfortunately, there was no significant recovery of CD4 T-cells in the lamina propria after treatment initiation. After 6 months of HAART all acutely infected treated patients had significant depleted lamina propria CD4 T-cells that persisted through 24 months of treatment. Markers of GI damage, inflammation and immune activation returned to baseline levels after 6 months of ART following an increase during acute HIV-1 infection (day 0). Despite the positive effect of early ART initiation on GI damage markers, the stark lack of CD4 T-cell recovery is disappointing. Fully understanding the complexities of HIV infection in GI tract remains a great challenge, but it is essential if strategies to promote CD4 T-cell recovery in gut are ever to materialise.

“To know your Enemy, you must become your Enemy.” The quote by Sun Tzu perfectly captures the theme of the session titled Defining and Targeting Residual Virus on cART.

And so Dr Keele presented an innovative molecular tag of SIV to help better understand the location, size and variability of persistent SIV infection in non-human primates. The “barcode” approach presented allows multiple viral variants to establish infection and then be identified over the course of disease progression. This will hopefully lead to the researchers tracking down the actively replicating viruses that are responsible for maintaining the reservoir and studying how this morphs once ART is introduced and subsequently ceased. Although non-human primate models seem far removed from the clinic, these models are essential for a better understanding of how and where HIV is hiding in the body.

Much closer to home comes the follow-up of a unique patient known as C135 who was part of the Sydney Blood Bank Cohort (SBBC) and infected with HIV 33 years ago. Infected with an attenuated ∆-nef strain of virus, C135 presented as an elite controller with 3 genetic polymorphisms associated with viral control, including protective HLA class I and HLA class II alleles, and CCR5∆32 heterozygosity – a truly distinct combination when accounting for the attenuated virus. Samples taken 15 years after blood transfusion indicated established HIV-1 infection, but in samples from 1997 onwards infectious HIV-1 has never been recovered from PBMC cultures and no HIV-1 DNA found in CD4+ T cells from either PBMC or gut biopsies. The patient has remained off ART since infection and presents a strong case for either viral clearance or at least sustained virological remission. Unfortunately, the current difficulty of sampling all possible reservoir sites in the body such as the CNS makes confirming viral clearance particularly challenging.

The session concluded with a late breaker from Dr Søgaard from Denmark, who presented the results of a clinical trial to assess the effects of romidepsin (an HDAC inhibitor) on the latent reservoir in 6 HIV-infected patients. The phase I/II clinical trial,  gave six aviremic HIV-infected adults intravenous romidepsin (5 mg/m²) once weekly for 3 weeks while maintaining cART. 36 adverse events were reported although the majority were mild and resolved spontaneously. Viral load increased from undetectable at baseline to readily quantifiable levels at multiple post-infusion timepoints in 5 of 6 patients (range 46-103 copies/mL after 2^nd infusion, p=0.007) – the first time this has been seen with an HDAC inhibitor. Furthermore, the emergence of quantifiable plasma HIV-1-RNA corresponded directly with the cyclic romidepsin infusions. However, the HIV-1 RNA levels returned to baseline a few days post infusion and no significant change was detected in total viral DNA across the 6 patients suggesting a transient effect of the drug and no permanent decrease in the size of the viral reservoir. Further trials with larger numbers of patients and/or in conjunction with other therapeutic interventions are eagerly awaited.

Professor Kate Dolan from the National Drug and Alcohol Research Centre, UNSW, presented data from their global systematic review of the HIV situation in prisons, which looked at imprisonment rates, HIV prevalence, HIV incidence, AIDS-related mortality, and services provided in prison, in the time period under observation from 2008 to 2013.

The review identified that 30 million individuals enter and leave prison per year, leading to the conclusion that good prisoner health is good public health, as any diseases contracted in prison, or made worse by poor conditions in custodial settings, returns to the community.

Drug dependence is a key factor in imprisonment in Australia, with 84% of people who inject drugs in Australia re-incarcerated within two years of release and the mean number of prison sentences sitting at 5. Whilst HIV prevalence is very low amongst Australian prisoners, transmission remains a risk and the prevalence of hepatitis B and hepatitis C has remained high.

Dr Fabienne Hariga, from the United Nations Office on Drugs and Crime then outlined a comprehensive package of 15 interventions for HIV prevention, treatment, and care in prisons, in particular looking at the introduction of needle and syringe program (NSP) into prisons, which she stated should be the number one priority.  

Dr Hariga outlined evidence from the evidence for action technical paper entitled Interventions to Address HIV in prisons: Needle and syringe programmes and decontamination strategies, which spoke to the feasibility and effectiveness of NSP in prison settings.

However, Dr Hariga conceded that current coverage of NSP in prisons is very low and many programs have not been sustainable to due strict controls implemented and a lack of confidentiality and anonymity, resulting in low uptake of the program by prisoners.

She concluded that a mixed model incorporating peer-based distribution, dispensing machines, and a health service, seems the best measure as part of a comprehensive package of interventions.

The Nursing Satellite Session

The nursing satellite session at AIDS2014 was themed “Nurses Stepping Up, Stepping Forward and Stepping Beyond!” to link to the conference theme of “Stepping up the Pace” and to provide an opportunity for celebration of the how the work of HIV nurses globally has a significant impact.

Kim Carbaugh, Executive Director of the US-based Association for Nurses in AIDS Care (ANAC) opened the session with a reflection on the UNAIDS 90:90:90 goal – 90% diagnosed, 90% on treatment and 90% on treatment with an undetectable viral load. However, there has been a lack of discussion in the main plenaries, or in any sessions, about the role of nurses in reaching these goals – and with 80% of the global health workforce being nurses, as Kim said, “We can’t get to 90:90:90, without the 80.”

Denise Cummins, a community HIV nurse from Sydney, then discussed her work over the past decade volunteering in Nepal, providing harm minimisation education, clean syringes, workshops and mentoring to people living with, or at risk of, HIV.

Her key message was that all nurses have skills that they can share with those in need and encouraged participants to contact local agencies when they travel and offer to help, even if just for a few hours. Why? to challenge yourself, for cultural exchange, to share your skills, to make a difference, to make friends and to have an adventure.

A/Prof Jason Farley, from Johns Hopkins University (JHU) School of Nursing, Adjunct Associate Professor at the University of KwaZulu Natal in South Africa and UTS in Sydney, and Adult Nurse Practitioner (NP) at JHU spoke about his work in upskilling nurses to manage multi-drug resistant TB (MDR-TB) in South Africa. As the majority of TB in South Africa is diagnosed by nurses, and nurses initiate treatment for non-MDR-TB, the next step in scaling up the response to the TB epidemic was to train and support nurses to initiate MDR-TB treatment.

Jason and colleagues explored whether primary health care nurses were able to safely and effectively initiate treatment for MDR-TB in South Africa, with the support of decision-making tools. Following appropriate training, mentoring and support, the study demonstrated that negative outcomes were not increased and final treatment outcomes were not worsened.

The successes demonstrated in Jason’s program, are so well recognised they have been incorporated into the National Strategic Plan of South Africa on HIV, STIs and TB 2012-2016, “…all primary care, antenatal, TB and mobile outreach health facilities must become fully functional nurse-initiated ART and MDR-TB initiation sites for adults, children and pregnant women.”

A/Prof Jane Tomnay from the Centre for Excellence in Rural Sexual Health (CERSH), University of Melbourne, outlined the model for a comprehensive and coordinated rural sexual health service, incorporating a nurse practitioner (NP), a workforce development network, expanding access to condoms and building GLBTI friendly rural services. Jane explored the benefits and challenges with working in a rural setting and discussed the path to establishing a self-sufficient sexual health NP model.

Sandra Gregson, from the Victorian Aboriginal Health Service, then talked about the model of HIV care and management available to Aboriginal people at the 2nd oldest Aboriginal Health Service in Australia. Conducting about 200 HIV tests/month, the recent new diagnoses have mainly been in Aboriginal people who are injecting drugs. The health service provides holistic care, with allied health and others services available or linked, to aim to engage clients in the improvement of their health and wellbeing in the long term.

Carole Treston, Chief Nursing Officer at ANAC, closed the session with a discussion about the role of nurses in advocacy and policy. Her message was a clear one: nurses, as one of the most respected voices in the community, can have an influential and powerful voice as public policy advocates and should step up and step forward to have their voices heard.

The session was very well attended and the participants were so grateful to have a session focused on the work of nurses.

Wednesday 23rd July 2014

After a long wait to see Bill Clinton address a packed audience to encourage us to continue to implement the goals of the WHO (and who addressed the gathering as a ‘movement’ rather than a conference), sitting in the special session on antiretroviral management in 2014—an interactive case-based discussion with several prominent HIV and hepatitis specialists—almost seemed ‘easy’ rather than trying to solve the complex public health problems of the developing world.

At the completion of the session, however, we were brought back to reality by a sobering statement from an African doctor who did ask that perhaps the next discussions could take into account the limited antiretroviral options in developing countries with likely scenarios from those regions, hitting home to me just how lucky we are in the Australian treatment environment to have so many choices.

It was also pleasing to see that when asked about simplification regimens for simplicity sake that several panelists were of the opinion that ‘if it isn’t broken, don’t fix it’ as we may switch patients to a less tolerable regimen with poorer adherence and without past records we may run the risk of archived resistance. The concepts of a ‘lateral switch’, where a patient has been naïve to treatment and there is minimal risk to switch versus a ‘vertical switch’ where we may not know of past suppression or resistance profiles was also discussed.

Links to the various guidelines can be found below:

1. ASHM 2014 Antiretroviral guidelines

2. US DHHS Adults and adolescents antiretroviral guidelines

3. American Society for the study of liver disease and the Infectious Diseases society of America: guidelines for hepatitis C treatment

Two very interesting studies from the Kirby were also presented this afternoon.

Firstly, Ben Bavington presented results from the Opposites Attract study looking at behavioural risk compensation amongst couples in the study. ‘Behavioural risk compensation’ being the concept where there may be reduction in condom use due to perceived protection from antiretroviral medications.

Approximately 77% of the HIV negative partners perceived their HIV positive partners viral load was undetectable, which was largely in accordance with pathology results. This did seem to correlate with engagement in condomless sex with approximately 73% HIV negative partners reporting condomless sex (CLS) when they perceived their partner’s viral load to be undetectable and thus demonstrating risk compensation within this group. Amongst the HIV positive partners, however, approximately 90% were taking antiretroviral therapy so perhaps this gave a protective effect.

In a separate session, Andrew Grulich presented on results of the SPANC study. This is an interesting area in that there is a 30-50% prevalence of high-grade anal lesions (HSIL) in gay men.

Treatment is difficult with recurrence rates of 50% at 1 year with grade 3-4 side effects. Progression to cancer is also 1/400 per year in HIV positive men and 1/4000 per year in HIV negative men. Of men recruited into the study they found that 1 in 6 men will develop HSIL per year (16/100 person years) with a clearance of 42/100 person years over 12 months.

HIV positive men were more likely to have HSIL but there was no correlation with age. HSIL was also very uncommon in men without chronic HPV infection. Pleasingly, with the high clearance rates, he concluded that if HSIL is identified that it does not necessarily require treatment and could be observed.

The session gave an overview of viral reservoirs, factors affecting latency and the complexity of latency between and within tissue types.

Dr Persaud from the United States began the session with the unfortunate news and analysis of the re-emergence of HIV infection in the “Mississippi child”. The researchers detected HIV-1 plasma RNA 27 months after earlier assays showed no virus present. Phylogenetic analysis of the virus confirmed it to be a 98% similar to the virus isolated from the mother, strongly suggesting reemergence from “viral remission” rather than the child becoming newly infected via another source.

Dr Van Lint from Belgium then gave a brisk yet detailed overview of viral latency mechanisms. She referenced studies which showed HIV-1 preferentially integrates into transcriptionally active regions of the genome and areas associated with clonal expansion when infecting T-cells.

Dr Van Lint also gave an overview of existing “anti-latency” agents such as vorinostat (SAHA), and newer agents such as Romidepsin, which may be more potent – very much needed if the approach is to be effective in virally suppressed patients on ART.

The presentation was finished with a description of the many cell-associated and viral factors involved in latency and thus the multitude of potential targets for anti-latency therapeutics. However, as research emerges on the complexities of HIV viral latency, it also highlights the heterogeneity of the mechanisms involved in latency within different tissue and cell types and even between individual cells. Any future therapies will need to accommodate this if they are to have any lasting benefit.

Dr Verdin from the United States reiterated the complex nature of viral latency and then described an innovative system using Green Florescent Protein (GFP) and other reporter genes to visualise a profile of genes associated with viral latency (both promoting and suppressing).

This produced a milieu of genes and related protein complexes involved, some known previously, others completely new to the viral latency field. An unexpected outcome of the increased understanding of the breadth of cell-associated factors involved in latency was the closing suggestion of considering therapeutic agents to increase or promote viral latency rather than suppress it (unlike the current experimental agents being trialled which aim to reduce viral latency). By targeting the integrated proviral DNA and “locking it in place”, away from transcription and subsequent virus production, the outcome could be similar to ART, but perhaps more potent?

Dr Chomont from the United States followed on by describing the heterogeneity within latently infected CD4+ T cells and the proportion of subsets infected within different patient groups such as post-treatment controllers and long-term non-progressors.

Both have higher proportions of latently infected cells with a more differentiated phenotype (which have a shorter turn over period within the body). He then described the role of early treatment on latently infected CD4+ T cells with mixed results.

For example Buzon et al. 2014 showed that early ART initiation did not affect the proportion of the more naive (and longer lasting) cells being infected.

However, research discussed by Dr Jintanat Ananworanich earlier in the day suggested that very early initiation of ART (2/3 weeks after infection) was associated with a reduction in the size of the reservoir in all CD4+ T-cell subsets, including the longer lasting central memory cells.

Dr Chomont also remarked that this benefit could remain even if treatment is delayed until 4-8 weeks after infection - still very early initiation within a real world setting however.

The session was concluded by Dr Melissa Churchill, from the Burnet Institute, Melbourne who presented on the role of tissue reservoirs and in particular the CNS. She described the role of the CNS as a probable viral reservoir citing multiple indirect studies, but also acknowledging the lack of conclusive and direct evidence.

Latency in the CNS is likely and, just as was reported in earlier presentations, so is the heterogeneity in latency between the different cell types susceptible to HIV infection in the CNS; astrocytes, macrophages, and microglial cells.

Dr Churchill concluded by discussing the potential role of current curative strategies (such as using histone deacetylase [HDAC] inhibitors) on the CNS with some caution – cell death within the CNS even if targeted specifically to latently infected cells would likely have negative consequences for the tissue and therefore the patient.

Away from the excitement created by Bill Clinton giving his Put Patient’s Health First to Improve Outcomes and Programme efficiency presentation today, a small group gathered for a Civil Society meeting on viral hepatitis called by the World Health Organisation (WHO). This informal meeting aimed to strengthen the engagement of civil society in WHO processes, enhance the dialogue on hepatitis-related work and build on the experiences of communities and groups living with, or affected b,y viral hepatitis undertaking advocacy work and providing services.  

Worldwide, between 130 and 170 million people are living with chronic hepatitis C and another 250 to 350 million are living with chronic hepatitis B—resulting in approximately 1.4 million deaths per year. Recognising the tremendous burden caused by viral hepatitis, this small event is one of a number of initiatives WHO is implementing, in order to build capacity and mobilise resources to respond to viral hepatitis. 

WHO established the Global Hepatitis Programme in 2010, following the adoption of resolution WHA63.18 (page 34) by the World Health Assembly, calling for a comprehensive approach to the prevention and control of viral hepatitis. Since then they have released:

• Prevention and Control of Viral Hepatitis Infection: Framework for Global Action (2012);
• Global policy report on the prevention and control of viral hepatitis in WHO Member States (2013); 
• Guidelines for the screening, care and treatment of persons with hepatitis C infection (2014);

and convened a Global Partners’ Meeting on Hepatitis to discuss the current status of the epidemic, levels of response in countries and future actions for enhanced hepatitis control worldwide. This meeting resulted in a "Call to action to scale up global hepatitis response" which puts pressure on the global community to increase access to prevention, diagnosis and treatment of viral hepatitis.

Furthermore, a new global resolution to promote a comprehensive response to viral hepatitis was adopted by the World Health Assembly in June 2014. WHA67.6 calls for enhanced action to improve equitable access to hepatitis prevention, diagnosis, and treatment and asks countries to develop comprehensive national hepatitis strategies.

At the event today the development of guidelines for hepatitis B and the development of a global strategy and plan for viral hepatitis which would include targets for the elimination of hepatitis B and C, were two of a number of initiatives currently being worked on by WHO demonstrating that momentum at global level is beginning to gather pace, but as we have learnt from HIV, there is a long road ahead, with much more collective action needed as we begin the journey.

Tuesday 22nd July 

In a program mixed with sessions on searching for a cure or simply arguing for the right for marginalised groups in developing countries to receive treatment, the oral abstract session titled ‘Antiretroviral therapy: not all strategies are created equal’ presented several studies of novel antiretroviral treatment.

The first presentation was presented by Eric Le Fevre who discussed the results of the MODERN trial, which was a phase 3, randomised, double-blind trial that compared triple therapy (TDF/FTC+DRV800/RTV100mg) versus nucleoside/nucleotide sparring, dual therapy (Maraviroc 150mg QD+DRV800/RTV100mg) in HIV positive patients naive to antiretroviral therapy.

Sadly at week 48 the study was terminated early due to inferiority of the Maraviroc containing regimen with only 77.3% subjects reaching the primary endpoint of HIV viral load < 20 copies/ml versus 86.8% of subjects on triple therapy.

Response was actually worse in subjects with a viral load > 100,000 copies and also in subjects with lower CD4 counts at baseline (200-350 cells) but pleasingly there was no emergence of resistance to study drug. Therefore, it still seems that a 3 drug regimen is still the gold standard for HIV therapy with possibly a greater benefit of including N(t)RTIs in the combination when treating subjects with a lower CD4 count.

Marina Klein from Canada then presented data on switching from a first antiretroviral regimen while virologically suppressed showing that it can be associated with increased risk of virological failure.

In Canada’s largest HIV treatment cohort (CANOC), 36% subjects switched from their original HIV treatment regimen, although the reasons for switch were not clearly identified – presumed to be for toxicity, simplification, tolerability or drug-drug interactions. Switching actually seemed to occur on average quite early at 0.8 years and was more common in women and people who inject drugs (PWID).

Klein reported that switching was more likely to be related to treatment failure, as identified as HIV VL > 1000 copies/ml, although did not present what proportion of subjects actually failed treatment. This does highlight some concerns about switching treatment and more specific switch studies should be considered before initiating switches in our patients.

And finally, Mark Boyd from the Kirby Institute in Australia presented interesting data from the Second-line resistance substudy, which aimed to examine the contribution of baseline N(t)RTI-resistance as well as other potential predictive variables to virological failure (VF).

Interestingly, they found that virological failure was associated with self-reported non-adherence, a higher baseline global genotypic sensitivity score (which should actually have indicated a better result), a baseline viral load of greater than 100,000 copies/mL, and race. He concluded that investment in effective adherence interventions and support are still needed.

The afternoon oral abstract session on pre-exposure prophylaxis (PrEP) was extremely well attended, showing a great interest in this area. There were two thought-provoking presentations from an open label ‘extension study’ of the well-known iPrEX study with the catchy title of ‘OLE’.

The first presentation by Kimberly Koester was based on 60 in-depth interviews of OLE participants. Interestingly and pleasingly, subjects stated that PrEP did not, in most cases, actually lead to increased condomless sex and condom use actually increased in younger participants. A major feature of being on PrEP was a decrease in stress, fear and guilt associated with sex. It would therefore seem that PrEP is being used as a supplement to existing HIV prevention strategies.

Jean-Michel Molina from France then presented interesting data from the Ipergay study that looked at high risk MSM who were enrolled in an ongoing, randomised, double-blind, placebo-controlled trial of ‘on demand’ PrEP with oral TDF/FTC.

Subjects were instructed to take 2 pills of TDF/FTC or placebo before sex (2 to 24 hours before), and 2 pills after sex (1 pill every 24 hours). Between February 2012 to May 2013, 153 patients were randomised with a median age of 35 years and median number of 2 episodes of sexual intercourses/week. During their last sexual intercourse (n=543), according to computer-assisted self report, 53% subjects used PrEP as scheduled, 28% used PrEP but did not follow the treatment schedule, and 19% did not use PrEP.

In order to look for drug concentration they collected blood and hair samples but only 59 hair samples from 38 patients were available for analysis – apparently not enough subjects had hair! TFV and FTC were detected in 51% and 49% of subjects in the TDF/FTC arm, and 14% and 0% in the placebo arm, respectively. 548 plasma samples from the first 113 randomized subjects were analysed. TFV and FTC were detected in 86% and 82% (75-100%) of patients in the TDF/FTC arm, and 4% (0-6%) and 3% (0-6%) in the placebo arm, respectively.

So despite variable adherence rates, there were acceptable levels of drug in plasma.

More interestingly, Robert Grant presented more data from the OLE study, especially looking at Tenofovir diphosphate levels in dried blood spots of subjects continuing in the iPrEX extension study. Those subjects with higher drug concentration levels and who reported ≥ 4 days of medication showed a 100% risk reduction in HIV incidence compared with a risk reduction of 84% with 2-3 tablets per week. Results of this study were published online today (July 22) in Lancet Infectious Diseases.

While vaccination offers hope for a large decrease in hepatitis B (HBV) in the future, many people today are co-infected with HIV and HBV, particularly in regions where both diseases are common.

Gail Matthews from the Kirby Institute in her presentation today described a huge global burden of disease attributed to HIV and HBV and HIV/HBV co-infection. Discussing the management of HIV/HBV co-infection, Gail Matthews noted that HBV co-infection presents unique challenges, especially in resource-limited settings.

Lack of access to routine testing and monitoring is described as one of the major challenges, which include:

• limited access to HBsAg testing, which means many co-infected individuals not identified pre-ART;
• little understanding of natural history of co-infection; liver disease fibrosis assessment not readily available;
• widespread absence of virological monitoring by HBV DNA testing.

Restricted access to Tenofovir in low and middle income countries, lack of routine screening of pregnant women for HBV and low coverage of universal infant vaccination in many countries are also described as the major challenges to the management of HIV/HBV co-infection.

Gail Matthews advocated for the changes at many levels including policy/advocacy, epidemiology, basic science and clinical research in order to overcome those challenges. These include: improved access to drugs; national testing policies; universal and birth dose vaccination; understanding of natural history of co-infection; management and incidence of flare; options for switch of treatment; and cure strategies.   

In keeping with the main theme of the AIDS 2014 conference ‘Stepping up the pace’, the first day of plenaries, oral abstracts and symposia sessions (amongst many other activities) focused on the so-called ‘Holy Grail’ of HIV medicine – finding a cure!

This largely focused on how can we identify HIV viral reservoirs and how we can eradicate them. While much of the science presented seems well beyond the scope of primary care, I felt the theme underpins the current debate of whether commencing treatment sooner rather than later is of individual benefit.

The opening plenary by Salim S Abdool Karim (Director of the Centre for the AIDS program of Research in South Africa) summarised the global response to HIV/AIDS over the last 30 years and pleasingly showed a global decrease in the number of new HIV infections in adults and children since the early 2000s. Less pleasingly though was the noticeable decrease in condom use in MSM in Australia between 2007 and 2011.

He also did theorise that the concept of elimination and eradication is not readily applicable to AIDS with the millions of people living with HIV/AIDS and that there is no cure available and that the key to the end of AIDS is ‘epidemic control’.

Jintanat Ananworanich, a paediatrician, immunologist and HIV researcher and now the Associate Director of HIV Therapeutic Trials at the US Military HIV research program in Maryland, USA, then outlined where we are in terms of an HIV Cure and where are we going. She introduced us to the concepts of the persistence of HIV in latent reservoirs and the difficulties of monitoring the elimination of HIV due to the fact that we do not have biomarkers to determine HIV remission.

She suggested that success will likely require combination approaches including early antiretroviral treatment.

This theme was continued in a special session on ‘The Future of Science in the HIV Response’ by Dr Anthony Fauci, Director, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethseda, USA, where he further outlined the complexity of the HIV reservoir in terms of having qualitative and quantitative characteristics. Qualitative components including the body (e.g. gut, peripheral lymphoid cells, brain), cell type (naiive and memory CD4 cells, monocytes, macrophages and follicular dendritic cells) and the status of the virus (defective or replication competent) and the quantitative aspect simply indicating the quantity of viral reservoir which increases after infection.

HIV viral latency is believed to form very early in HIV infection and the various methods to eradicate HIV include:

• ‘flush out’ the virus or the so called ‘shock and kill’ method (use of latency activator therapies such as Panobinastat)
• immunotoxic therapy
• stem cell transplant
• gene therapy to eliminate CCR5 (Zinc-finger-nuclease modification of CCR5)

Dr Fauci also emphasised that a combination approach would be needed to achieve sustained virologic remission; early treatment initiation would “stack the deck in favour of eradication” by limiting the seeding of the reservoir, while use of novel immunotherapies (including passive transfer of HIV specific antibodies or therapeutic vaccination) would help eliminate HIV and HIV-infected cells. In addition, he outlined that recent advances in our understanding of the ‘broadly neutralising antibody response’ as particularly important in controlling the virus.

These concepts were further discussed in an afternoon abstract session that will be covered in another post.

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In the Hepatitis Co-infection session today, Sanjay Bhagani from the Royal Free Hospital, London described co-infection with hepatitis C for a person living with HIV as “double trouble” for the liver.

He began by looking at the D:A:D study which examined the causes of death in 49,734 HIV-infected patients followed in the period from 1999 to 2011. In this study liver-related diseases were found to be a frequent cause of non-AIDS related death, responsible for 13% of deaths.

A second study showed that persons co-infected with HIV and HCV have liver fibrosis stages similar to those without HIV who are nearly a decade older, with progression shown to be faster even when controlling for alcohol and other co-morbidities. Bhagani also demonstrated that hepatotoxicity was more common in co-infected patients even with modern HAART.

It was not all bad news, however, with the era of Direct Acting Antiviral (DAA) based therapy now a reality. Bhagani outlined results from a number of trials looking at interferon-sparing and interferon-free therapies, which revealed similar SVR rates in co-infected patients as in mono-infected patients.

Such results have meant the EASL recommendations on the treatment of hepatitis C released in April 2014 state that the same treatment regimens can be used in HIV/HCV patients as in patients without HIV infection, as the virological results of therapy are identical. Bhagani advocated for the need for an improved cascade of care and access to treatment for people living with HIV and HCV, due to the aggressive, multi-system impact of co-infection.

In 2010, young people aged 15-24 accounted for 42% of new HIV infections in people aged 15 and older.¹

The adolescent HIV population presents a unique set of challenges when it comes to education and behaviour change. Adolescence is a time for exploring sexuality, experimenting with risk-taking behaviour and finding new ways to connect that sets them apart from the adult world.

How can we reach young people to prevent new HIV infections?

Moving health messaging into the digital gaming space, says Lynn Fiellin and colleagues at Yale University who presented their results at the Young People Epidemiology and Prevention Strategies oral abstract session at AIDS 2014 today.

Digital health technologies are growing at an unprecedented rate, particularly in the smart phone and tablet space. Mobile phone networks are now reaching up to 85% of the global population and the World Health Organisation estimates close to 5 billion mobile subscriptions worldwide.²

A recent infographic reported the State of the Mobile 2013:

•      91% of all people on earth have a mobile phone

•      56% of people own a smart phone

•      80% of time on mobile devices is spent inside games or apps

•      Majority of teens play video games as long as they have access to them.³

And the largest audience of apps and video games?  Adolescents - the digital natives or our techno world.

'Serious Gaming' is an emerging platform for imparting health messages and delivering health education. Serious gaming holds the promise of delivering HIV prevention messages to teenagers through game-based learning.

Anyone who has talked to a teenager lately knows that gaming experiences can be engaging, immersive and educational. Many Australian schools now set homework where students are using video gaming platforms and apps to entice and encourage literacy and numeracy and to connect and collaborate with remote schools.

Applying health messages to video games has the potential to improve health literacy around HIV and STI and may go some way towards prevention.

Studies into serious gaming cite neuroplasticity improvements, faster processing, increased cognitive flexibility and a deeper creative learning experience as just some of the results reported by young people who took part in serious gaming compare to those who played non-educational games.⁴

Today, Fiellin and colleagues showed that when teens were randomly assigned to 10 hours of gaming sessions that included: HIV knowledge, self efficacy, risk perception scenarios, short vs. long term priorities and an epilogue illustrating the consequences of their choices, their HIV risk knowledge had improved at 6 weeks, with knowledge levels maintained at 3 and 6 months.

Participants enjoyed the gaming experience, found it challenging, and reported that they felt responsible for the decisions made during game. 

During question time, criticism of the study was aimed at the game's apparent representation of heteronormative and gender-based stereotypes. Ms Fiellin agreed that the video game was limited in its choice of characters and diverse sexual orientation but that the research group now have proof of concept to develop the game further including the potential for a multiplayer platform.

References

1.  UNAIDS Fact sheet Adolescents, young people and HIV www.unaids.org/<http://www.unaids.org/en/media/unaids/contentassets/documents/factsheet/2012/20120417_FS_adolescentsyoungpeoplehiv_en.pdf>
2. World Health Organisation (WHO) Website. Tobacco Free Initiative. www.who.int/tobacco/mhealth/<http://www.who.int/tobacco/mhealth/en/index.html>
3. www.digitalbuzzblog.com/State of the Mobile<http://www.digitalbuzzblog.com/infographic-2013-mobile-growth-statistics/>
4. Glass BD, Maddox WT, Love BC (2013) Real-Time Strategy Game Training: Emergence of a Cognitive Flexibility Trait. PLoS ONE 8(8): e70350. doi:10.1371/<http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070350>

In 2011, Australia signed the United Nations 2011 Political Declaration on HIV/AIDS that sets 'bold new targets' for HIV/AIDS to 2015. Signatory countries agreed on the following 'strong, time-bound' targets by 2015:

▪   Advance efforts towards reducing sexual transmission of HIV by 50%

▪   Reducing HIV infection among people who inject drugs by 50%

▪   Push towards eliminating new HIV infections among children

▪   Increase the number of people on life-saving treatments to 15 million globally

▪   Reduce tuberculosis relation deaths in people living with HIV by half

The UN Declaration highlights action areas for improving universal access to HIV prevention, treatment, care and support. Public access to sexual and reproductive health services, particularly for women and children, are a cornerstone of 'working towards a world without AIDS'.

HIV in Australia

It's a given that Australia is better placed than many countries to meet these targets. And there is no better time to take action. Australia's HIV rates increased by 8% in 2011 and campaigners are saying that Australia have 'dropped the ball' on HIV/AIDS research and funding in recent times. 

In 2013, 1,236 people were diagnosed with HIV, similar to levels in 2012. For more information and a snapshot of HIV in Australia, the AFAO website features a short summary HIV in Australia Statistics Update 2013.

Despite some progress being made over the last 18 months, barriers to tackling rising infection rates remain. These include a lack of access to rapid HIV tests licensed for use in Australia, prohibitive treatment costs and unhelpful restrictions on people with HIV and their medical teams deciding when to start treatment.

The Melbourne Declaration

To strengthen the United Nations goals and reduce HIV infection rates in Australia, the Melbourne Declaration was launched in October 2012.

Action areas in the Melbourne Declaration include:

▪   Making rapid testing widely available in clinical and community settings

▪   Enhancing access to and uptake of antiretroviral treatment for HIV

▪   Making HIV pre-exposure prophylaxis available to people who at high risk of HIV infection

▪   Fast tracking treatment licensure and funding

▪   Mobilising and informing people with HIV, and in populations at high risk of HIV, about advances in treatment and prevention

▪   Support ongoing, high quality HIV research.

With the 20th International AIDS Conference in Melbourne comes renewed calls for action, leadership and commitment to get Australia back on track, and to help meet UN targets by 2015.

Show your Support.  Sign the Melbourne Declaration today!

You can follow the proceedings of the International AIDS Conference 2014 from the 20-25th July 2014 on Twitter using the hashtag #AIDS2014

Watch out for tweets from the #AIDS2014 Conference:

@AFAO

@ASHMmedia

@eGPSolutions

@MelbDeclaration

@RedRibbons2012

Further Reading

Bold new AIDS targets set by world leaders for 2015 

Melbourne Declaration Update 

HIV in Australia Statistics Update 2013

A sombre and moving opening to the MSMGF Pre-Conference as delegates killed in the shooting down of flight MH17 were honoured by a minute’s silence and tributes from plenary speakers, including Don Baxter and incoming President of the IAS, Chris Beyrer. Beyrer in particular pointed out that the tragedy highlighted the strong coalition that drives the HIV response, with researchers, activists and policymakers travelling together and losing their lives on the flight. Beyrer went on to encourage strong engagement at the conference, highlighting developments in biomedical prevention in particular. However, he acknowledged the risk of leaving behind vulnerable populations, particularly men who have sex with men in countries which feature violent suppression of homosexuality. Achieving basic coverage of HIV prevention in these contexts remains extraordinarily difficult.

Michel Sidibe, Executive Director of UNAIDS, emphasised how the violation of human rights of men who have sex with men and transgender people in many countries poses such a threat to the HIV response, fuelling stigma, discrimination and violence and preventing people from accessing HIV prevention and treatment. Sidibe implied that it is difficult to see how we could achieve bold global targets without fighting to protect the rights of all people affected by HIV and by encouraging peace, security, equality and health. Sidibe concluded by saying, ‘no more to exclusion, bigotry and AIDS.’

My colleague, Peter Aggleton, from the Centre for Social Research in Health, UNSW, gave a plenary presentation in which he argued that the current fixation on scientific solutions to HIV often appears to neglect the ways that people live and behave, failing to harness the creativity and passion of affected communities. Taking something of a risk at a conference with MSM in the title, Aggleton highlighted his role with others in creating the category ‘men who have sex with men’ to help describe a range of homosexually active (or not so active) men. Peter said that those ‘experts’ never realised the force that the label MSM would gather around itself, making invisible complex cultures, practices and identities. Aggleton highlighted the ways in which the professionalisation of the field, including the community sector, often distances activists and educators from the communities with which they work. He concluded that we need to remember the anger and passion that kept the concerns of gay, bisexual and other ‘MSM’ central to the response to ensure that biomedical strategies like ‘test and treat’ and PrEP are critically evaluated rather than unquestioned and imposed.

The final plenary speaker, Kene Esom from African Men for Sexual Health and Rights, argued eloquently for a nimble range of diplomacy, activism and engagement, both loud and public as well as quiet and behind the scenes, to challenge violence, educate policymakers and advocate for the rights of LGBTI people so that HIV prevention can gain purchase in more countries in Africa.