It seems to be the ultimate irony that a cure has been found to treat Hepatitis C ( HCV) and we can't afford it. That the world's 180 million people infected with HCV now have access to daily tablets with tolerable side effects and could be free of the virus in up to 12 weeks is remarkable.

However, the estimated cost of achieving this at today's prices would be $US 15.1 Trillion, close to the US GDP of $US 16.7 Trillion. Add to this dilemma the nature of HCV transmission and high rates of re-infection in some settings, and the subsequent recurring costs, and this makes the task of eliminating - let alone eradicating - HCV seem unachievable. It also lends support for the need to implement other strategies which reduce transmission of infection and for the obvious need to develop a vaccine.

Professor Greg Dore from St Vincent's Hospital and the University of NSW, in Sydney Australia, provided an eloquent account of the priorities and strategies he proposes for tackling treatment as prevention. (The prevalence of chronic HCV in Australia is 280,000.)

He proposes a strategy which provides for:

• Programs to increase testing/screening (in Australia this has already been well covered with 85-95% of cases detected).

• Programs which enhance harm reduction for people who inject drugs (PWID) through needle syringe programs (NSP) and opiate substitution therapy (OST).

• Prioritised treatment so that "the transmitters", those most likely to transmit HCV - particularly the under 25yr old PWID who are more likely to share needles more often - prisoners, MSM (and pregnant women) are treated early.

• Increase treatment rates in those with more advanced liver disease who have a more imminent risk of severe morbidity and mortality.

Professor Dore modelled a scenario where 8% per year of PWID in Melbourne are treated. Using this projection he predicted elimination of HCV in Melbourne by 2027. His proposal that a rapid scale-up of treatment be implemented in the PWID group, so that high transmitters are treated contemporaneously and removed as sources of reinfection for each other, seems to provide a possible solution to this problem.

Currently there are no interferon-free HCV treatment regimes subsidised in Australia. Hopefully this will change in the near future with clinicians, stakeholders, patients, government and Pharmas negotiating prices that are more affordable, as have some of the developing countries who have used their huge economies of scale to negotiate relatively low cost supplies of HCV antiviral drugs.

We all look forward to a world free of the suffering and stigmatisation associated with HCV infection.

A new term  "condomless anal intercourse"  (CLAI) replaces " unprotected anal intercourse" due to the acknowledgement that different strategies are used by MSM to reduce their risk of or " protect" themselves from contracting HIV when having sex without a condom. Some of the strategies include:

- Serosorting, such that HIV negative men only having CLAI with other HIV negative men

- Negotiating a regular ongoing relationship where both men are tested and if both are HIV negative they make an agreement not to have CLAI outside the relationship.

- Withdrawal method (of the penis prior to ejaculation)

- Strategic positioning during sex so that the HIV negative man takes the insertive role and the HIV positive man only takes the receptive role

- Viral load sorting, so that CLAI takes place only when the HIV positive partner's viral load is undetectable

- Pre- exposure prophylaxis (PrEP) used and the HIV negative person only engages in CLAI once he is taking ART on a regular basis

There were four presentations on this topic, the details of which can be seen in poster presentations at CROI. Some of their important observations include:

- The Centre for Disease control observed that  in the U.S. CLAI has increased between 2005 and 2014 in both HIV concordant and discordant sexual encounters. This trend was not different for men on or not on ART. It was not possible to conclude whether reliance on treatment explained the difference.

- in a Seattle seroconversion cohort of newly diagnosed MSM there was evidence of large and sustained serosorting behaviour changes which would have potential for reducing HIV transmission to HIV negative men.

- in a review of Philadelphian Local National Behavioural Surveillance data serosorting was common amongst African- American MSM but of limited safety because of the low level of testing, with 60% not having been tested in the last year

- in a Nigerian study looking at the use by MSM of sexual positioning and serosorting, undiagnosed HIV was present in 20% of those engaged in serosorting.

In the interesting question and discussion time some of the issues raised were:

- the need for collection of data which provides more detailed information about seroadaptive behaviours

- the need for clinicians to have conversations with patients about reducing risk of acquiring or transmitting HIV. There was acknowledgement that the most effective recent developments coming out of recent studies and presented at this conference support the impact of treatment as prevention and the goal of achieving and maintaining an undetectable viral load using cART in order to make HIV Transmission unlikely.

- regular/ frequent testing is essential for enabling early treatment and to reduce transmission but also to improve the effectiveness of serosorting behaviours. Clearly, serosorting in a context of low testing and high rates of undiagnosed HIV is a perilous strategy. 

- the acknowledgement that there is a problem with increasing STIs in HIV positive men, and also the problem that HIV avoidance behaviours are not the same thing as STI avoidance and hence don't mitigate that risk.

Some important findings pertaining to seroadaptive behaviours pertaining to viral load sorting and also to treatment as prevention can be seen in the interim results of the Opposites Attract Study, an Australian study lead by Andrew Grullich and Ben Bavington ( Poster 1019). The study aims to establish whether HIV transmission in homosexual HIV serodiscordant couples is greatly reduced when the HIV- positive partner is receiving combination ART and has an undetectable viral load, as has previously been seen in studies of heterosexual couples. To date the study reports that there have been no linked HIV transmissions in 150 couples over the 2 years follow up. This finding is extremely important and will offer considerable reassurance to gay serodiscordant couples having CLAI.

The PROUD and IPERGAY studies offer us 2 dosing options for effective HIV prevention in high risk MSM:

1. Daily Truvada (Tenofovir/ Emtricitabine) 1 tablet

or

2. On- demand Truvada at the time of sexual exposure as follows:

- 2 tablets 2-24 hrs before sex

- 1 tablet 24 hrs later

- 1 tablet 48 hrs later

( if additional sexual encounters then continuing the regime so that 2 tablets over 48 hrs are taken after the last sexual encounter)

With the addition of PEP provided on-demand

Some additional considerations:

• Adherence to PrEP is obviously critical to its effectiveness
•  Condom use should continue to be promoted. Although neither study showed an increase in incidence of STIs in the PrEP group there is an ongoing concern that increased risk taking behaviour on PrEP will increase STI incidence.
• Side effects- most commonly GIT - nausea, diarrhoea, less common- headache, renal
• Renal monitoring- baseline and ongoing (? Frequency)
• Baseline and ongoing HIV and STI testing ( 3 monthly)
• Possible targets for PrEP- High risk MSM. For example anyone- with an STI in the last 6 months, in a HIV discordant relationship, who has unprotected anal sex, who use recreational drugs and/or binge drinks.

Take- home messages for GPs with patients with HCV

1. There are much more effective Hep C drug regimes becoming available that produce high cure rates.

- in general terms the newer drug regimes, called Interferon-free Direct acting antivirals (DAAs), are achieving >95% cure rates in HCV genotype 1, and not much less in HIV co-infected patients.They are daily oral tablets as opposed to previous injections, better tolerated and require much shorter durations of treatment (usually 12wks) than previous regimes.

- HCV genotype 3 requires a different drug regime to Genotype 1. More recently treatment has changed from Pegylated Interferon and Ribavirin (PEG/INF/RBV) regimes to Sofosbuvir and Ribavirin for 24wks.

- in HIV co- infected patients on cART( combination anti-retroviral treatment) some regimes increase risk of renal toxicity and renal impairment and so regular renal monitoring, including  serum Creat, eGFR, Phosphate and urine Protein/ Creat Ratio, usually  on a 2-4 wkly basis is suggested in early treatment.

- remember to consider cART and HCV drug-drug interactions.

2. Diagnostic testing- "if you can't identify who your patient's are you can't treat them"

- in at risk patients test antibody to Hep C (Anti-HCV) and if positive then do HCV RNA , understanding that in early infection there is a sero-negative window where HCV RNA won't be present and hence you should repeat the test again a few weeks later.

- early diagnosis is even more important in order to enable early treatment with a view to preventing progression to cirrhosis, liver failure and cancer in those who develop chronic hepatitis but also importantly to prevent virus transmission to others ( treatment as prevention).

- remember that upto 50% of patients spontaneously clear the virus, most of those within 2-6 months.

3. In HCV/ HIV Co- infection liver disease is accelerated. There is a 3x risk of progression, which is also more rapid, to cirrhosis and decompensated liver disease.

4. Clinicians, including GPs should determine the severity of liver disease using clinical examination, laboratory tests- including Bilirubin, PT, INR, Albumin. In addition, other specialist investigations are used to determine hepatic fibrosis, include non- invasive imaging such as Fibroscan and direct serum biomarkers such as Fibrospect II. Liver biopsy is usually preserved for instances where there is discordance in the other results. Tools such as the Child- Pugh- Turcotte Score ( CTP) and the Model for End stage Liver disease (MELD) help to determine disease severity and to guide management decisions

5. Be aware that 5-7% of Child's A ( mild) cirrhotics progress to decompensated liver disease each year and hence regular review, at least 6 monthly, is recommended.

6. Screen for Hepatocarcinoma. Remember that in those with chronic disease and liver fibrosis cure does not remove the risk of hepatocarcinoma.

7. Consider organising Gastroscopy to screen for oesophageal varices.