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.

HIV Co-infections, hepatitis B, hepatitis C and TB

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No impact of HIV on HEPC treatment outcome

95-97% cure rates even in co-infected

Improvement in quality of life occurs v. Quickly with new oral medIcations due to suppression of the Hep C virus.

If there is cirrhosis of the liver, treat for 24 weeks. De compensated cirrhosis may be reversible, but not always.

In Australia, HIV/HCV co infected numbers approx 2,500-3,000

 

At this morning's IAS plenary Professor Greg Dore from the Kirby Institute and St Vincent's Hospital in Sydney gave an excellent presentation on the exciting treatment options soon to become available for Hep C, and described some studies he is currently involved in.

The development of interferon-free HCV therapy provides one of the major advances in clinical medicine in recent decades. 

Major recent developments include:

  • There are now several highly effective IFN-free DAA regimens for genotype 1
  • HIV has no impact on HCV treatment outcomes
  • HCV resistance testing is of limited clinical relevance
  • Some treatment individualization may still be required (e.g. cirrhosis)
  • Decompensated cirrhosis is reversible, but not always
  • Shorter duration (6-8 weeks) pangenotypic regimens are in development

In the treatment of GT1, the presence of resistance mutation Q80K may compromise treatment response to simeprivir/sofosbuvir if cirrhosis is present, but treatment outcomes improve if the treatment period is increased from 12 to 24 weeks.

Treatment of GT3 will likely need combination with one of the NS5A inhibitors.

Professor Dore described "perfectovir", the ultimate therapeutic agent for Hep C, the holy grail which the pharmaceutical companies are striving to develop.  The attributes of "perfectovir" would be:

  • Extremely high efficacy
  • Well tolerated
  • Once daily dosing
  • Pangenotypic
  • Short duration (6-8 weeks)
  • Affordable

The cost of these new DAAs is the major barrier.  Broadened access to IFN-free HCV therapy would provide the foundation for HCV treatment as prevention.  This could be looked at in high risk populations such as incarcerated people and people on opioid substitution therapy programs.

Professor Dore went on to describe 2 interesting studies.

The STOPC study looks at HCV treatment as prevention in 5 Australian prisons.  The primary objective is to evaluate the impact of a rapid scale-up of IFN-free HCV treatment on HCV transmission.  The primary endpoint will be a change in HCV incidence from pre- to post- scale-up of IFN-free HCV treatment.  The baseline HCV prevalence in this community is 24%.

The CEASE study looks at co-infected populations, and again evaluates the impact of a rapid scale-up of IFN-free HCV therapy on HCV transmission among people with HIV, with the primary endpoint again being a change in incidence from pre- to post- scale-up.  This study is very much underpinned by the March 2015 recommendations of the Australian PBAC for use of the new DAAs sofosbuvir, ledipasvir and daclatasvir, with no restrictions based on stage of liver disease or injecting drug use.  The hope is that primary care S100 prescribers who currently manage co-infected HIV patients will start prescribing for HCV, and ultimately be able to provide this treatment for HCV mono-infected patients.

In summary, the arguments for IFN-free therapy access for all as presented by Professor Dore are:

  • IFN-free therapy is an enormous advance in therapy
  • HCV-specific QOL impairment in early disease, reversible
  • Potential HCV treatment as prevention benefits
  • Non-treatment = ongoing monitoring, potentially for decades
  • Drug price curve will continue downwards
  • Ability to cure empowering for entire hepatitis C sector

 

 

 

Tagged in: IAS2015

HCV: new frontiers and controversies was the final session I attended, abstracts 179 to 181.  It built on the earlier workshop, HCV in the interferon-free era, blogged by Jane.  In the pathogenesis of acute infection, Ashwin Balagopal described a doubling time of 7.5 hours with 21 days to reach a viraemia of over 6 logs. HCV infects a minority of hepatocytes at 20-45% with about 100 copies of HCV RNA per hepatocytes. 1-3 trillion copies of RNA are made daily and rapidly cleared to maintain set point. 20-25% of people clear infection, usually within the first six months, and prior clearance of an earlier infection makes this more likely (as does being female, non-African and HIV negative).  In reminding us of ELITE controllers, he raised the vaccine option. 

IL28B is now known as interferon lambda 3 which can mutate to IFN L4 to which HCV binds differently. Evidence of immune response is also seen in that neutralising antibodies from people who have cleared HCV previously have an effect in a further clearance of infection.  

Greg Dore first defined terminology in his HCV treatment as prevention talk.  There are three approaches: eradication as in small pox, elimination in which the incidence is zero but on-going work is required (measles and polio) and epidemic control where incidence decreases over time. 

The dilemma in HCV treatment is whether to focus on the liver disease burden in older people (defined as over 35) or on HCV infection prevention in younger people. He presented data which indicated that 75% of people aged 15 to 19 years had ever injected, this rate falling to 25% over the age of 35. 

In discussing treatment as prevention in Australia in the 10% co-infected with HIV and HCV, he reported on the CEASE study: approximately 80% of co-infected people have been diagnosed, around 80% of those are linked to / retained in care but only about two thirds are / have received treatment.  Of the treated fraction, HIV RNA is suppressed in over 60%. 

He spoke of the harm reduction approach for PWID, noting that only 41% of countries have NSP programs and only 30% have opiate substitution programs.  HCV incidence in Australia was around 25% per annum in the 1990s falling to about 5% per annum in the 2000s.  The target groups for treatment as prevention are PWID, prisoners (12% of injectors are jailed annually with an incident HCV infection rate of 10% per annum), HIV positive MSM and pregnant women.  

He outlined the STOP C study of early and deferred treatment with sofosbuvir and GS5816 for 12 weeks planned for two medium to maximum security prisons in New South Wales. 

In abstract 181, HCV therapeutics: It's the virus stupid, Mark Sulkowski described the HCV life cycle and where the directly acting molecules fit.  He also spoke of the class cross resistance seen (in the low number of people who fail treatment) to date with telapravir and daclatatasvir and of the benefit in preventing failure in adding ribaviron. 

He define Perfectovir, introduced by Greg Dore in the preceding talk, as achieving SVR in > 90%, working for all genotypes, administered as a once daily pill and with no side effects.  He also thanked all the people who were in clinical trials which did not show benefit.  

Marion Peters had given a superb talk in the HCV workshop on HCV cirrhosis with early decompensation in which she demonstrated the usefulness of the Childs Pugh score as well as the MELD during treatment for assessing decompensation.  She had reminded us that the natural history of ESLD is that 5-7% of people decompensate annually.   In this the last talk of the conference, she was given the title of HCV therapeutics: big sticks with big stickers. In noting that SVR produced a 70% reduction in HCC and a 50% reduction in all cause mortality (renal and bone disease, cryoglobulinaemia, lymphoproliferative disease, CVD and cognitive impairment) as well as reducing portal hypertension. 

Cost effectiveness of staging determined treatment as opposed to treating all patients yielded a best result for immediate treatment of anyone with a Fibroscan score of > F1. The cost of treating T2DM, HIV, HER2 positive breast cancer and HCV with IFN RBV and a PI were about the same but the difference is that the costs with HCV treatment are all up front, not spread out over time.  A time delay in treatment (until people reached Medicaid age in the USA) meant two thirds had at least one other chronic disease which could complicate treatment.  

91 countries across the world to date have made deals of various sorts with pharma to access treatments for their populations.  The obvious inequities were discussed in question time.  

Marion Peters ended her talk saying that the problem is the patient load of HCV infection worldwide and that in its management of HCV, Australia could be considered the greatest country in the world. 

Tagged in: croi2015

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.

 

Tagged in: croi2015

Cindy Zahnd reported on data modeled from the Swiss HIV and hepatitis C Cohort. Specifically the considered the impact of deferring treatment initiation in HIV-HCV co-infected patients. There was not difference starting in a month or 12 months. But treatment outcomes were heavily impacted by fibrosis score at treatment commencement. Delaying till F3 doubled the risk of disease progression and delaying till F4 saw a five fold increase.

Interestingly patients with F4 were more likely to have a serious or fatal liver event even after having had an SVR on treatment. This is probably because even though the virus was cleared irreversible damage was sustained. A salient message for clinicians and patients who might be waiting for the next best drug to come along.

You can view this and other coinfection oral presentations from the http://www.croiwebcasts.org/ it was session O-12 Curing hepatitis C: Mission accomplished

 

Please join us for a memorial event celebrating the life of one of Australia’s leading HIV advocates, Levinia Crook… https://t.co/N7dof5xaGa

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