The bottom line is that as far as I know nobody has done a trial that looks like:

Take 2 DAAs for the entire 12-24 week time

Go for total viral death with a third DAA at the END of the treatment course when your liver and body will be in the best state it has been in for years.

Should this be 12, 8, 4 or even 2 weeks Ribavirin?

We know that steady state blood levels are reached in 5 half lives of a medication so with Riba having a multiple dose half life of a massive 12 days you should theoretically do more than 60 days to get maximum effect. It is an exponential ascent towards an asymptote which in english means that we ascend to the maximal level in a way that looks like:

So we never get to 100 but get ever increasingly close.

It works the same way going down which is why it takes a couple of weeks to come good if you stop Riba due to anaemia. The level in you blood takes 12 days to fall the 1/2 what it was when you stopped.

Disclaimer: This is outside the published guidelines but what I might do if forced to choose.

We can see experts suggest 12 weeks Riba is enough and that makes sense based on the half life.

We know things get better on treatment.

So if doing 12 weeks Riba I would consider doing the last, rather than the first 12 weeks with Riba, particularly in the difficult situation of someone F4 with low platelets.

Psychologically it would probably be easier to add Riba as an insurance having first felt the benefits of 2 strong DAA, expecially for those who have done it tough on PEG/Riba.

The side effects people got on PEG/Riba may have been more PEG and less Riba than we thought. I have a good dozen patients who are relapses telling me it’s much easier than they expected and their numbers look good.

Then again I just took one patient off Riba because after 18 weeks he was getting sick both on the numbers and in spirit. He’s feeling much better now and we are getting some blood cells back.

Q

These two comments are much in line with the discussion I had with my hepatologist about suitable treatment for myself.

For the first one, I always thought the sides seemed to cycle around the weekly injection, not all directly afterwards but still cyclic rather than constant as you would expect with daily Riba.

And as I have cirrhosis and will be retreating the recommendation was that 24 weeks looked the best option, hitting it hard from the start with the view to going full term but the possibility that Riba be cut short if I can’t tolerate for numbers (or I guess spirit). I agreed this as my best option for guaranteeing success.

But I’m not sure how this translates to SShady43 without cirrhosis as I felt my specialist seemed to think Riba’s effect was at least partly based on it’s ability to better impact the virus in scar tissue, etc. (I hope I’m am paraphrasing him correctly here.)

Is generic Simeprevir available ?

Is generic Simeprevir available ?

I wish someone could answer that question Paul.Before begining tx on 24wks sof dac riba I tried everywhere to find a source of generic simeprevir to replace the riba.My specialist was not against the idea even though he pointed out the data on the combination was thin .There is a trial in place at the moment called the Impetus 2 In the end I had to stick to the riba,which fortunately,so far,has not been the problem I expected.
Dr Freemans idea of taking the riba in the last 12wks or less, is a novel one.It would be interesting to hear an opinion from Graham Foster,the riba Guru on that one.

Just a caution that the sof/dac/sim arm of this trial (reported in AASLD LB #23) comprised 6 people from the easiest group to treat and they were further selected as being in the 66.7% with the highest RVR during the initial 48 hrs of the trial. So, promising for the future!

And I do believe that we will hear a lot more about triple DAA treatments and hopefully they become the “silver bullet” for this horrible disease. The idea of fast, sides free treatment is fantastic!

OTOH as of now, extended treatment +/- Riba has been shown to improve the odds in difficult to treat cases such as those who have relapsed and particularly those with high fibrosis/cirrhosis.

I have enquired with all the manufacturers claiming to have Simeprevir on Alibaba.

Of those that responded none of them either had it or was willing to sell it.

We continue to look.