ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Michael Moso

Michael Moso

Michael is a medical resident with the Infectious Diseases Unit at the Alfred Hospital, Melbourne. He works as part of the inpatient team managing patients admitted acutely or electively for HIV management. Michael has been heavily involved in HIV research and has previously completed an Honours year in HIV latency with Prof Sharon Lewin. He continues his research with the Infectious Diseases Unit at the Alfred and will be presenting his research on HIV and CKD at this year's conference.

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PrEP has been a major discussion point in the 2017 ASHM conference. In a joint symposium with the 2017 Sexual Health Conference, multiple speakers spoke of the rollout of PrEP in Australia and New Zealand. A/Prof Edwina Wright discussed ‘PrEP in Future Australia: How will it look?”

 

Edwina invited us to imagine the future of PrEP in Australia if PBS listing were to occur in 2018. One of the key points made was the need for rapid up-scaling of PrEP provision in the community. There have already been signs of over-saturation of clinics involved in the current PrEP studies, and PBS listing of PrEP would likely further overwhelm these resources. This leads to the question of which providers would be able to assist in providing appropriate PrEP counselling  – other practitioners besides medical practitioners could play a role here, including nurse practitioner and pharmacists. Criteria for PBS prescribing would likely exist to obtain authority – this would be based on the recently published ASHM guidelines on PrEP and would require individuals to be HIV negative, have normal renal function and aged over 18.

 

Another key issue raised by Edwina as well as numerous other speakers during the conference relate to inequity of access. Currently those accessing PrEP come from a similar demographic – gay, educated, Australian-born and employed individuals. Individuals from culturally and linguistically diverse backgrounds, those from lower socio-economic status, and those in rural communities are under-represented. Further strategies are required to try and reach out to these communities.

 

Another issue that requires further investigation is that of potential toxicity. As PrEP contains TDF, the long-term risk and toxicity to renal function or bone health remains to be determined. A PrEP registry could play an important role here to allow long-term follow-up of potential toxicity. Continuous follow-up of individuals on PrEP also remains vital, not only in assessing for potential complications, but also for ongoing routine screening of other STIs.

 

This session highlighted the need for increasing preparedness of clinicians in the community in being able to manage and counsel patients requesting PrEP, the number of which is likely to increase if/when PrEP becomes PBS listed. In addition, those currently accessing PrEP through clinical trials may prefer to see their general practitioners or other health practitioners in the community to continue receiving PrEP once the trial ends. Several PrEP resources are available to clinicians including the ASHM PrEP guidelines and an online PrEP module available on the ASHM website. 

There were several great talks given on the final day of the ASHM conference. The morning HIV&AIDS symposium s100 prescriber session, entitled ‘changing landscapes in therapy’, discussed current and future issues pertaining to antiretroviral therapy, their interactions with other medications and their role in co-morbidities. Professor Mark Boyd from the University of Adelaide gave an interesting talk on ‘When is 2 drugs better than 3’. Antiretroviral therapy (ART) has often been referred to as ‘triple therapy’, reflecting the current guidelines and current practice of prescribing 3-drug combinations to achieve full virologic suppression.

 

This has come to question recently with a few trials completed or ongoing that assess dual therapy vs standard triple therapy. There are obvious benefits to dual therapy – reduced pill burden in the ageing cohort would have the effect of reduced drug interactions, as well as possibly improved adherence and drug tolerability. In the same session we heard from Ms Krista Siefred from St Vincent’s about polympharmacy and its associated adverse effects, as well as from pharmacist Ms Alison Duncan on the complexities of drug interactions between ART and other medications. Simplification of ART regimens would greatly assist in these matters

 

Mark presented several studies comparing dual therapy vs triple therapy. A meta-analysis was performed comparing this, looking at effect on dual vs triple therapy on virologic suppression. Overall, pooled results did not demonstrate a superior result for triple therapy over dual therapy for both viraemic patients and patients switching ART. In more recent studies using integrase inhibitors, again dual therapy (including a dlutegravir + lamivudine regimen, or an intramuscular cobotegravir + rilpivirine regimen) was shown to be non-inferior to standard triple therapy for virologic suppression.

 

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Although interim data looks promising, long-term safety and efficacy of dual therapy is still yet to be fully examined. As such, it is not yet recommended for clinicians to routinely change patients to dual therapy regimens, although this switch may be a feasible option in the future.

 

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Prof Damian Purcell from the Peter Doherty Institute in Melbourne presented some exciting research in this morning’s Late Breaker session looking at novel HIV latency reversing agents in the pursuit of an HIV cure.  We have heard previously about the ‘shock and kill’ approach to HIV cure, where latently infected cells are stimulated to produce new virus production with the aim of inducing cell death without activation. There have been several clinical trials using a variety of latency reversing agents (LRAs) including the histone deactylase inhibitors (HDACi) vorinostat and romidepsin. However, although these drugs were able to stimulate HIV transcription, they did not reduce the pool of latently infected cells. In addition, these drugs are non-specific and have an effect on all cells, even those uninfected.

 

Damian spoke of a model developed by his laboratory to target latently infected cells with full-length provirus containing the viral protein Tat. Using a cell line model with various reporters, his team was able to screen a library of drug-like compounds to assess latency reversal that is specific to Tat-containing (i.e. HIV-infected) cells. Multiple ‘hits’ were obtained from the screen, and narrowed down to 1 potential compound that was tested using CD4+ T-cells obtained from virally suppressed patients.  This compound was classed as an amidothiazole and was shown to increase unspliced HIV-RNA in patient-derived CD4+ T-cells ex vivo. It is thought to exert its latency reversing activity through interaction with the methyltranferase complex. This compound was also found to synergise with another class of LRA known as bromodomain inhibitors.

 

Identification of this this novel compound is exciting as it provides another step towards finding the ideal LRA that could be targeted towards latently infected cells while minimizing effects on uninfected cells. However, there is still further research required to see its efficacy in reversing latency – an important step would be to identify whether this compound actually stimulates production of functional virus (rather than just unspliced RNA). Further research into its safety profile would also be necessary.  

In the session on ‘Initiation, testing and diagnosis’, Dr Mark Bloch spoke of a new device that could be used for rapid HIV self-testing. The concept of rapid HIV testing has been around for some time, however it is not yet readily available in Australia. Mark spoke of the many benefits self testing could provide: possibly increasing uptake of testing and thus diagnosis – particularly for those in hard to reach communities (there is predicted 10% undiagnosed people living with HIV in Australia), as well as increased convenience, confidentiality and sense of autonomy. Of course it is not without risk – the potential for inaccurate results, ethical risks, and potential psychological danger in the event of a positive result in an environment without clinicians readily available to answer questions.

 

Mark’s study looked at the usability and performance of a new device – Atomo Galileo HIV self-test. In 521 individuals, concordance of the self-test was assessed with the conventional laboratory testing, and usability was assessed by assessing accurate performance of 6 critical steps. In this study, concordance of the self-test with lab testing was essentially 100% (99.8% - the 1 discrepancy was attributed to a false positive from the lab test). There was high usability scores demonstrated by close to 90% of all individuals performing all 6 critical steps.

 

The device itself looked simple and intuitive. It was not too dissimilar from a glucometer or a pregnancy test – with a lancet to prick the finger and chamber to collect blood (in the same device). A single band appeared in the event of a positive result alongside a control band. The test reportedly takes approximately 15 minutes to obtain a result.

 

This device has potential for use in difficult to access communities and resource limited settings, and removes additional barriers to testing and diagnosis. It remains to be seen what impact HIV self-testing will have in engagement with clinics and whether this would impact adherence to regular screening guidelines for other STIs.

 

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Mark directs us to his website ‘HIVST.org’ for further information on HIV self-testing.

HIV infection in young people in Australia has thus far not been well characterized. In the  ‘Trials, Treatment and Toxicity’ session, Dr Carly Hughes from Monash Medical Centre in Melbourne used the Australian HIV observational database (AHOD) to compare demographics between adolescents/young adults (13-24yo) to those over 25years. She described the need to further characterize the population of young adults who are newly diagnosed, given the complexity adolescence and young adulthood places on management of chronic diseases. This has been experienced in other sectors such as patients with type 1 diabetes. Main points from the presentation:

 

-       223 new diagnoses of HIV were made in those <25 years of age since 1997

-       A significantly higher proportion if females are represented in new diagnoses made in young adults (<25years) compared to over 25

-       The <25yo group had higher CD4 counts and lower VL at diagnosis, but this difference was lost at time of treatment initiation

-       There was significantly higher loss-to-follow up in the <25yo group  compared to >25yo (incidence rate of 8.8 vs 4.68 per 100 person years)

-       There were significantly higher rates of treatment interruption in the <25yo group

 

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Data from this study highlights the challenges of managing adolescents and young adults with newly diagnosed HIV and the need for additional methods to engage younger adults in medical care. Social support networks could play a role here - the opening plenary talk by Nic Holas on ‘Living with HIV online’ discussed the growing role of online support networks for people living with HIV. He described the role his online support network , 'The Institute of Many' (TIM), has played over the last few years in providing another avenue for people living with HIV to obtain information and find additional support. Clinicians could play an increasing role in this space to help engage younger individuals.

There has been a large shift in the practice of HIV medicine towards that of chronic disease management and management of co-morbidities. One such co-morbidity is osteoporosis/osteopenia – the incidence of which is increasing, driven in part by the ageing HIV population, as well as ART-related effects such as tenofovir disoproxil fumurate (TDF) use. In the session on ‘Trials, Treatment and Toxicity’, Prof Jenny Hoy from the Alfred Hospital and Monash University discussed her findings on a recently completed randomized trial looking at the bisphosphonate zoledronic acid versus TDF-switching on bone mineral density (BMD). Main points from the talk:

 

-       TDF has previously been shown to cause lower BMD and increases fracture risk (TAF has been shown to have less of an effect on BMD than TDF)

-       Switching from TDF to another agent shows improvement in BMD

-       Zoledronic acid has also previously been shown to increase BMD vs placebo in HIV-positive individuals

-       The trial was a randomized, open-label 2-year trial testing zoledronic acid (5mg) vs switch of TDF to alternate ARV (in most cases to abacavir or an integrase inhibitor) on BMD at time 12 months and 24 months

-       43 patients were analysed for the zoledronic acid group and 42 for TDF-switching

-       There was significantly higher increase in BMD in the zoledronic acid group compared to the TDF-switching group (6.1% vs 2.9%) at 12 months, which continued to increase in the zoledronic acid group at 24 months (7.4% vs 2.9%)

-       The study was not powered to comment on changes in fracture rates

 

Overall the study demonstrated significant increases in BMD in patients treated with zoledronic acid compared to TDF-switching, however it remains to be seen whether this translates clinically to reduced rates of fractures. Given the ageing cohort of the HIV population and predicted increase in osteopenia/osteoporosis, coupled with previous data demonstrating increasing frailty – risk of fractures remains an important clinical concern. Clinicians should aim to screen for and manage risk factors for co-morbidities early. This was summed up in Prof Georg Behrens opening plenary talk– to consider a ‘hit hard and early’ approach to HIV co-morbidities.

 

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