Hi everyone. I am 61 years old and have had HCV type 1 since age 25 when I briefly experimented with injecting drugs. I had Interferon monotherapy in 1999 while living in New Zealand but it was unsuccessful and I suffered with depressed mood, horrible flu like symptoms and developed severe tinnitus which I still have. A nasty treatment but although it was unsuccessful, I seem to have come through it all with less lethargy and my ALT has been mostly just outside the normal range since 2000. My fibroscan result this year averaged 5 so luckily I seem to be holding up reasonably well. I have been watching the development of sofosbuvir since the early days of it's development by Pharmasset and was so excited by it's eventual release to the market by Gilead until the shattering disappointment of how ridiculously expensive it is. I don't think that Australia is going to pay the sort of money that Gilead want and I have decided to bite the bullet and buy my supplies through the assistance of the Buyers Club. I have been watching with interest the development of new treatments and I think that Gilead's days of best treatment monopoly will soon be over. A small Australian bio-pharmaceutical company called Benitec Biopharma has been developing a one shot cure for all strains of HCV and is currently in phase 1/11a of a first in man trial in the USA with no safety issues identified so far and early indications of efficacy hopefully before the end of 2015 or in early 2016. This is a very exciting development and I think that if they are successful big Pharma will have to come to the party in drastically reducing the cost of current treatments before they are superseded by this amazing development which could be a real gamechanger in the way we treat not only HCV but also HBV and other diseases. Unfortunately it will be a few years and further trials before this technology becomes available but it offers hope to all of us suffering from this virus that a better treatment may be in the wings and that current treatments should become more affordable within Australia in the not too distant future.

As you note the data is currently inadequate to be definitive. With 15 kPA on your fibroscan you are F4 and with that the cirrhosis sub groups are the ones most applicable to you. 24 weeks of treatment will be required.

On first principles we observe with HIV there has been a progression from 1 to 2 to 3 (or more) medications and HAART - Highly Active Anti Retroviral Therapy. Given HIV and Hep C are similar there are probably useful lessons but it is still experimental.

Looking to mechanisms:

• Sofosbuvir is a pan genotypic RNA polymerase inhibitor
• Daclatasvir is a pan genotypic NS5A inhibitor
• Ledipasvir is an NS5A inhibitor
• Simeprevir is an NS3/4A inhibitor
• Ribavirin is a guanosine analog (fake RNA component)

Failure to clear represents the selection of resistance. The way I explain it to patients is like this:

• You have 1000 soldiers and you shoot them all with a machine gun
• 100 were wearing bullet proof vest so you walk along with a sword and chop their heads off
• 10 "idiots" put their vests on wrong, covering their necks so you drop rocks on their heads
• 1 "idiot" put the armour plate meant for the front of the vest on his head....

Each drug has what is known as a log kill. A log kill of 1 kills 9:10, 2 kills 99:100

Log kill reflects the fact that for any one drug there are typically some survivors and the next drug's job it to "take them out". It makes sense that the next drug should use a different mechanism to taking Ledipasvir + Daclatasvir would not make much sense because either one can inhibit NS5A for GT1b.

If all of Sofosbuvir + Daclatasvir + Simeprevir were available it's hard to argue that would not be gold class.

If you want to go totally experimental Ribavirin has been shown to provide impressive results in cirrhotics with Sof + Dac so HAART in Hep C might end up as: Sof+Dac+Sim+Riba.

The fundamental problem with small trials is the margin of error. At n=100 this is +/-10% so the 96.6% you might read should really be 96.6% +/- 10%. In other words the confidence intervals of the various options overlap making it impossible to be definitive.

Your priority is more about starting than choice because fibrosis is progressive but regresses in the face of reduced or zero viral load. The more fibrosis you have the harder it will be to get to cure.

Hi berri,

I don't think you opened a can of worms. She wanted to kill that thread. The complete lack of any reasoned, logical, informed argument is always a dead give away in my experience.

Haven't emailed Greg since start of treatment. Just because I figure he's really busy. But I'll be sending him a copy of my VL when I get it next week. FBC and LFTs done at 2 weeks - everything within normal range. Huge ncrease in my energy levels.

Nope, no sides so far. I'm keen to hear about people's experiences on treatment too so will email. Cheers. Glad you tracked me down.

Meant to say that Greg's blog on the hep mag site wasn't updating but the homestead one is.

hepatitisctreatment.homestead.com/generic-harvoni.html

But now the hepmag site has too. Hadn't seen his latest post until just now. Strangely, just yesterday, I was marvelling at my own new found hole digging abilities too.

I relapsed after Boceprevir + Ribavirin + interferon a couple of years ago. I am G1. My problem was white & red blood cells dropping dangerously low resulted in lowering of dose. I've been worried about what resistance might have developed ever since, so I'll be closely following this topic. Here's something I just found that's rather hopeful:

www.ncbi.nlm.nih.gov/pmc/articles/PMC3961994/ This study includes the following paragraph [Note DCV = Daclatasvir]:

"A combination of DCV and a nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, sofosbuvir, with or without ribavirin for 24 wk achieved SVR in 100% of untreated HCV genotype 1a and 1b patients (n = 44) as well as in HCV genotype 1a and 1b patients (n = 41) who failed to respond to prior treatment with telaprevir or boceprevir, peginterferon and ribavirin. SVR was achieved in 93% of patients infected with HCV genotypes 2 and 3 (n = 44)[89,90]."

41 patients who failed telaprevir and boceprevir must surely have included people with resistant varieties. Interesting that the excellent result was achieved both with and without Ribavirin.

Hi Miko,

My personal experience: I've been treated with Simeprevir+interferon+ribavirin. The Simeprevir side effects were by far the worst. I thought I was going to die. Once I finished the Simeprevir part of the course, the interferon side effects were, in comparison, just mildly unpleasant.

Also, no bike riding on Simeprevir. After the first week, every time I went out, my skin started peeling off, and I grew big, red blisters on my eyeballs. After the second week, I was bed ridden. On top of that, the treatment was totally ineffective.

On the other hand, maybe Simeprevir will work for you.

I'm wanting conformation for treatment of Hepc 3. I have imported the new treatment via Greg Jefferys. I have mild scarring and lower than normal platelets. I'm taking a three way combination of Sofosbuvir/Daclatasvir and Ribavin for 12 weeks. Some of the information differs saying a 24 week course is best. Can you offer clarity on this.
Kind Regards,
Vicki

I want to get hold of these drugs ASAP before the window of opportunity closes. It may take me 2-3 months however, to organise the time off work to do the treatment (I tend to get bad side effects). So I'm wondering how long I can keep Sofusbuvir, Daclatasvir and Ribavirin in the fridge before commencing?

Hi Vicki,

The 2015 EASL report is widely considered to be a benchmark document on treatment types. I'm pretty sure it's available elsewhere on this forum, but I've attached it to this post.

At the moment, in Australia a private prescription would be the only way to access the medications, although as far as I know nobody has any stock.

The proposed and pending PBS listing is and S100 listing.

S100 is not a - do the S100 course and you can prescribe S100 medications.

It is a do the S100 HIV prescriber course and you can prescribe S100 HIV medications (but not any other S100 medications).

So when the PBS listing happens it will be under S100 - well at least that's what the PBAC suggested. At that moment Infectious Disease Physicians and Gastroenterologist will probably be "grandfathered" ie given S100 rights because of experience/qualifications.

GPs will need to do a specific course, pass an exam, and then (probably) spend X days/consults with an approved S100 prescriber to get their ticket.

This process is exactly what was required for me to be able to prescribe methadone. A 2 day course at Sydney University. An exam. And then to actually get the ticket you have to sit in with someone and see some patients.

Only after doing all that can a GP get their ticket to prescribe.

It's a good process that makes sure people prescribing know what they are doing, but it is also a barrier.

Hep C patients are unusual in that as a group they are very, very well informed about the best treatment, but with things like Daclatasvir that have a lot of interactions to consider it's a little more complicated than meets the eye.

I've been fortunate to have experts offer me personal advice. For example one expert pointed me to

www.hep-druginteractions.org/checker

Which is a great tool for checking drug interactions. At his unit they use it all the time and file it in the notes.

Now I know about it I use it all the time, but it was important need to know stuff that when I met patient zero I simply did not know.

Hello Vicki,

If you are < F3 then 12 weeks Sof + Dac should do.

If F4 then 24 weeks Sof + Dac +/- Riba

F3/F4 is grey.

Fibrosis is a spectrum. F0 vs F4 is easy. At the upper middle....

I have my test results. And i have been denied treatment by my insurance company. i want to get generics through the buyers club it seems like its my only hope.

Thanks Dr. Freeman. I had a fibroscan about a year ago and don't have my results at hand but I remember being shown the chart and I was on the very low end about a centimetre in to the left hand side; if that helps. The specialist at the Liver clinic wants me to have a Biopsy, which I'm avoiding. I have read that the fibroscan is a much better indicator of liver scarring??
The Specialist also said that it was hard to tell if I had any cirohsis as some of my blood tests showed I might; recent fatty liver deposits and lowish platelet count. But, some of them that I don't have scarring. He recommended a the 12 week Sof/Dac course. I have only imported 12 weeks of Sof/Dac - I also received 12 weeks of Ribovirin with the Sof from India.
After reading further blogs and different Pharma trial reports, I leant that people with cirrhosis only have a 68% clearance rate using the Sof/ Dac treatment for 12 weeks. So...I stated taking the Ribovirin two days into the treatment. I'm taking 2 x 200mg capsules twice a day.
I'm not sure if this is even the right dose to add to the Sof/Dac..
I have an appointment at the Liver Clinic tomorrow and hope to clarify the situation. I'm not sure how they will respond and want to treat me because I have imported my own Generic meds. What should I expect and ask. Should I insist on another Fibroscan? Will the result of the scan I had a year ago be sufficient?
I will read over the ESL report you attached too, I have read it before but I've got a bit of information overload at the moment and am feeling anxious about my interpretations.
I realise I've got my self a bit muddle with all of this and am learning every day. I'm sure it will get sorted. I would really appreciate your opinion before I go to the clinic tomorrow.
Thank you so much for your time and efforts.
Kind Regards, Vicki

Thank you Dr James.I just wish someone like you was supervising my treatment.Unfortunately you live at the opp end of the continent.
I hope you eventually get the peer recognition you deserve for your humantarian efforts.

PKQ.Your post on Simeprevir scares the living daylights out of me.It does not seem to tally with the reported results of trials.But then they are often drug company sponsored.
Is there anyone else out there reading this that has had a similar experience with Simeprevir?

I'm 51 and found i was hepc+ about 15 years ago.
Around 10 years ago I went on 6 months of Interferon/ Ribavirin which failed to clear the virus.
i have just contacted Concord Hospital in Sydney to send me the forms to access my files - 3 weeks minimum

I only remember that I had a genotype which was among the most difficult to treat
And my liver biopsy showed quite a bit of damage - i think on a number system i was 1 number below cirrhosis

When i went on the treatment I was very fit and healthy.
When i was on the treatment I was constantly sick and a nightmare to live with (I don't do sick well)
I felt crap for a year, had enough of doctors and constant blood tests
i was told the virus had cleared, but then told that it had come back??
It was a terrible year of my life, and i have dismissed the thought of any sort of treatment since

The article in the SMH which put me onto this site interested me though
It has brought all the bad memories back and I am very nervous, particularly as i may need ribavirin as well for best outcome

So i guess my questions are
How do i find out what specific treatment I will need, and what will be the side effects
Do I need to get my 10 year old files from the hospital to find the genotype i have
Or do I need to go for a new round of tests to determine best treatment

Once i have this info i can make an appointment with Dr Freeman and assess my options

Thanks all - this is a great group - pharma companies suck