TOPIC:

Greetings all,
i have a question to pose regarding Ribaviron.. I am geno 2a, and relapsed after 12 weeks tx with Sov/Riba. Eager to start new tx with Sov/Dac for 24 weeks.. What's the feeling about adding Ribavirin to the mix? After the headaches, heartburn, hair loss and CONSTANT battle against cold sores popping up, I'm wondering if taking the Riba again would even be worth it. Will taking it again give me enough of a boost that it would be worth considering, or have some of the bugs now become resistant and taking the Riba would all be for naught? Thanks for the input!!

From this video which has been posted several times already, it appears 12wks of riba adds about a 5% advantage in cirrhotic or hard to treat patients.
So far I have not been able to find the answer to the question of whether 24wks of riba has any significant advantage over 12 wks.

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:

Half Lives	% Increase	% of max
1	50	50
2	25	75
3	12.5	87.5
4	6.25	93.75
4	6.25	93.75
5	3.125	96.875
6	1.5625	98.4375
7	1.5625	99.21875

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.

Hi Dr. Freeman,
I think I understand this. But to be sure, if I were to add riba to my sof/dac, I would want to take it nearer the end of my tx. Sounds like add riba to the last 84 days of treatment would be good? Sorry; I am getting ready to order meds and am just really unsure if I need or want to do this, but of course I really DO want to wallop the hell out of this virus. Maybe I just bite the bullet and add it in later to be sure.
Many thanks!

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.

Hi Doc Freeman,

There was a school of thought, I am sure you are aware, that advocated using your biggest guns up front in a tx. The thinking was to kill off as many resistant mutations as possible before they became emergent. From a virology point of view this made sense to me.

If I read you right, you are reasoning that adding riba at the end, not the beginning, could make it more tolerable, both physically and psychologically, especially for an F4 situation. This also makes sense to me.

So, if tolerability is not an issue, say somebody is F1, all blood tests normal, what would you do? Hammer the virus at the beginning to try and prevent any stray hangers on, or hammer it at the end to finish them off?

Thanks, dt

Q

James-Freeman-facebook wrote: 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.

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.)

There is a late breaker from the AASLD conference. It shows that SOF Dac and Simeprevir are the ultimate weapons. Very soon it will be apparent that three way combos of drugs already available will do the job in as little as one month.

It's late breaker number 23 if you want to read the full story.

A third weapon is the answer to replacing Ribavirin not prolonging the course to six months,

They cured some easy to treat patients in THREE weeks. Surely we should be looking at adding Simeprevir instead doubling the time frame of treatment.

Is generic Simeprevir available ?

Kinda available .... in that it's there but nobody that's talking has tried it so we don't know who the actual manufacturers are and who are the middle men and who are the scammers.

But take a look ....

www.alibaba.com/trade/search?fsb=y&Index...earchText=simeprevir

Note that some claim medicine grade and others don't, and there is what appears to be finished API form and another intermediate form

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.

Well it looks like my question was partially answered 1 min before I posted.I think it would be necessary to pay to have any of those selections tested before taking them,unless someone else has had experience of their probity.

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.

www.natap.org/2015/EASL/EASL_30.htm

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.