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
- Short duration (6-8 weeks)
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