There is ongoing optimism surrounding the evolving management for Hepatitis C.  But this is also tempered by the enormity of the epidemic of Hepatitis C around the world.  Whilst ~250,000 Australians living with Hep C will potentially have access to PBS subsidized highly effective directly acting antivirals in the coming months, there are still 80 million people worldwide living with hepatitis C with the vast majority in Africa (22 million) and Asia (12 million).  Many of these people do not know they have Hepatitis C (i.e. they are not tested).  We were also shown a sobering figure illustrating that the global burden from liver disease is increasing more rapidly than any other disease (including cardiovascular, respiratory, diabetes) and hepatitis C has now overtaken hepatitis B as the leading cause of liver-related morbidity and mortality in the world.   

An example of the mortality impact of hepatitis C was starkly demonstrated in a US study.  They showed that the median life expectancy was 78 years (without HCV or HIV), 60 years (with HCV) and 52 years (with HCV/HIV co-infection).  And as populations in high income countries like Australia grow older, the proportion of liver transplants and liver cancer due to hepatitis C continues to rise.

Well, let me end on a good note for those living in Australia.  We look forward to the first interferon and ribavirin-free single tablet regimen (Harvoni = Ledispavir + Sofosbuvir).  This drug has already been given to more than 200,000 people treated outside clinical trials and is proving to be a real game-changer for the traditionally difficult to treat patients with HCV genotype 1 (>95% SVR after 8-12 weeks in treatment naive).  Viekira-Pak has also been recommended by PBAC for those with genotype 1.  It is also exciting to see that pan-genotypic regimens like Sofosbuvir + Daclastavir has also been approved by PBAC for genotype 3.  Here's hoping that PBS listing will come in Dec 2015 or early 2016.

Jason Ong

This question continues to be a vexing one with our definitive answers coming in probably 5 years time.  There is increasing evidence that AIN3 is a precursor to anal cancer but the problem is that we can screen for AIN3 (anal cytology, high resolution anoscopy) BUT we don't know two fundamental pieces of information.

1)  How do we treat AIN3 effectively?  To date, we have seen many treatment modalities trialed but AIN 3 is highly recurrent.  A triple arm trial in 146 HIV+ MSM reported by Dr. De Vries examined a group of HIV+ MSM who were screened by high resolution anoscopy and histopathologically confirmed to have AIN.  He then randomized them into 3 groups (16 weeks of imiquimod, 16 weeks of 5-FU or 16 weeks of monthly electrocautery).  It was disappointing to see that recurrence rates were high for all patients at 72 weeks (67%), imiquimod users (72%), 5FU users (58%) and electrocautery (68%).  When stratified by perianal vs. intraanal lesions, the peri-anal lesions did better.  

2)  Which men with AIN 3 should we treat?  As Dr. Mary Poynthn from the SPANC team demonstrated, nearly half of HIV+ MSM had detectable high-grad SIL (HSIL) and there was a high regression rate for AIN3 (~39 per 100 person years).  These figures almost match the "success rates" of many treatment modalities.  We need better tools to distinguish the AIN3 that are more likely to progress onto anal cancer (e.g. use of biomarkers like E6/7?).

Until the above 2 questions are answered, I would not suggest implementation of anal cancer screening using anal cytology/HRA.  The alternative is to undergo tertiary screening (i.e. early cancer detection) through regular DARE for those at highest risk (HIV+ MSM who have 100 times greater incidence rates compared to the general population) until more evidence is established for anal cancer screening.

We had a wonderful symposium tonight where key HIV clinicians, researchers and community members came together and oozed optimism for the 'PrEP program'.  And I deliberately emphasize that PrEP is not just about taking a pill but a program i.e. users take Truvada and be engaged with their health provider in getting regular HIV/STI and kidney function testing (3 monthly).

There is no doubt about PrEP's effectiveness with the latest studies (PROUD and IPERGAY) showing 86% effectiveness in reducing HIV seroconversion.  But if PrEP was used daily, effectiveness approached 100%.  

It was interesting to see data from San Francisco (Street Survey) showing that 63% of PrEP users reported condomless anal intercourse with 6 or more partners in the last 6 months. This is important because PrEP is being used by those at highest risk for HIV (or in the words of Prof Bob Grant - those who are "popular and affectionate"). There is ongoing debate about who should access PrEP.  Should it be only dispensed to those at highest risk for HIV as defined by the current Australian PrEP guidelines? This remains a contentious point as a modelling study by David Wilson from the Kirby has shown that PrEP was cost-effective only if we dispensed it to those at highest risk. However there was a strong sentiment in the room to allow PrEP to be freely available to whoever wanted it.  

Even if we agreed that anyone should be able to choose to be on PrEP, access is still an issue in Australia.  Although we are starting to see many clinics throughout Australia prescribing PrEP, access to Truvada can only be obtained by importing the drugs from overseas through online pharmacies like www.aids-drugs-online.com or www.alldaychemist.com  This is approximated to cost ~$88/month.  This may still put PrEP out of reach of those who are socioeconomically disadvantaged.  So it was heartening to hear from A/Prof Darren Russell that the HIV Foundation in Queensland is launching a program to allow access to PrEP to those who are financially disadvantaged.

Another interesting point from the panel of speakers was that PrEP had multiple fringe benefits including empowerment, and healing of prior trauma and fear.  This was emphasized particularly from current PrEP users.

It is difficult to determine how many people in Australia are currently using PrEP but we may still be at the stage where PrEP users are the innovators or early adopters.  But as the community continues to grow in their experience of using PrEP, we may see this becoming an important part of the armamentarium of HIV biomedical prevention.
 

We kickstarted the conference with an update on potential vaccines for STIs by Prof Ian Frazer, the co-founder of the HPV vaccine.  He gave a 'passing grade' on his STD vaccine score card for vaccines against Hepatitis B and HPV vaccinations but major innovation is needed for vaccines against treponema pallidum, neisseria gonorrhea, mycoplasma genitalium, trichomonas vaginalis and H. ducreyi.  There was some sad news and exciting news.

The sad news was that there was a marked disparity between rollout of HPV vaccine programs and cervical cancer prevalence.  So, the countries that have the highest rates of cervical cancer (mostly on the African continent and South Asia) have no HPV vaccine programs currently.

The exciting part of his talk was around his work on a vaccine against Herpes Simplex Virus.  Whilst a previous paper in NEJM 2012 Jan 5:366 (1):34-43 showed some protection in HSV 1-2 uninfected women against HSV-1,  the protection conferred was not significant enough to warrant further development of that form of herpes vaccine.  However, Ian Frazer's group is now looking at a herpes vaccine using newer technologies (now in phase 2 trials) that may show greater promise.  Watch this space!

Jason Ong.