TOPIC: How long to wait before retreatment

Hi Meg,

After your comment about the percentages I went back and did some research as previously I took your comment of 95% for 8 weeks and compared that to the overall 12 week results for F0-1 1b's of 99% per the combined ION trials. Anyway, I found this report where comparing like for like in the ION 3 trial the difference was actually 2.3%. So not a huge difference but significant if you are one of those patients. A closer look shows ION 3 naive for just 1b as equal at 98% for both lengths. Personally I think I would be more comfortable with 12 weeks but maybe have a chat with Dr James?

hcvadvocate.org/hepatitis/factsheets_pdf/GT1_Harvoni.pdf

And the eight week treatment doesn't actually increase the risk of resistance as such. However doing 12 weeks Tx means there will be a better chance of SVR and if you SVR then you can't develop resistance.

Hi Gaj I hear you! Yes I have spoken to my GI in Brazil as well as to Dr Freeman ( on a GP2U consultation) and both have told me that since I already have the third bottle of generic harvoni with me and unless I develop real bad sides from now on (I complete 9 weeks of tx tomorrow) It is better to do the 12 week tx - in spite of meeting the 8 week guidelines - as an insurance and reassurance of SVR. So I cut a deal with myself so to speak and I will play by ear and see how my 9 week labs and ultrasound results will come out next week. I am very curious specially about level of fibrosis - if it had a regression. Thanks again for "following" up on me and all your support.

Hi again! Going back to the original topic I just saw on a facebook Hep C forum that someone who thought had relapsed at SVR12 is now UND at SVR24! Something Dr Freeman said at the time - about two months ago- to wait until next bloods to make sure it was really a relapse. It wasn't. Such happy news I just had to share it here. Also a good example (there must be lots and lots) that it is better not to rush into re-treatment - unless there is a F4 and psychological aspects that Dr Freeman mentions in his OP.

Many NS3 RAVs resulting from treatment generally disappear by themselves in about more than 1 year. Ns5b sofosbuvir-emergent RAVs - in about less than 1 year.
However, acquired NS5A RAVs persist, requiring retreatment with drugs having considerably different resistance profile/mechanism of action/high bareer to resistance.
Results from a small 3-year follow-up study (presented at AASLD 2016).

www.natap.org/2016/AASLD/AASLD_61.htm

There are drugs in development that target not the virus, but host proteins, and were shown to work in early trials. However, different direct acting antiviral drug combinations were also shown to be effective for retreatment in many cases.

I find the whole "wait for the RAVs to become un-measureable" logic flawed.

Accepting the observation that some RAVs become unmeasurable over time, to me the question is "does that matter?"

Go with me on this.

Say you have no measurable RAVs at baseline, and treat, but fail. What does this mean? It means you MUST HAVE HAD RAVs at baseline, despite the fact we could not measure them, and this is why you failed.

Post treatment we may be able to see the RAVs (because we have killed just about everything else) but we need about a 10% population to see them. Now consider this:

Starting viral load 1,000,000
Limit of detection 10

Almost all patients become undetectable (99.5%) but 5-10% fail to SVR. It follows that when they are undetectable they have < 10 RAVs, or to put it another way from that initial population of 1,000,000 there were only 0.001% RAVs

Conjecture - generally RAVs are at such low levels we can't measure them, despite the fact they exist.

Now with biological systems we see decay in terms of 1/2 life - the time taken for something to fall by 1/2. If it takes say 1 month for RAVs to fall by 1/2 it will take 2 to fall to 1/4, 3 to fall to 1/8. Even at this rapid rate it will take 20 months for 1 million RAVs to decay to 1 RAV (2**20 == 1 million).

To me one of the best reasons to delay retreatment is to wait for better, more potent drugs and particularly triple and quadruple regimens.

If this was HIV nobody would suggest waiting to RAVs to decay before changing regimens but prices are different and there are more options about that.

The first of my originator Harvoni failures are coming through at SVR12 and 24 following 24 weeks generic Sof+Dac+[Simeprevir or Asunaprevir]+Ribavirin. The Simeprevir was originator out of Egypt, and the Asunaprevir originator out of Russia

The combinations of Viekira-pak+Sofosbuvir and Zepatier+Sofosbuvir, both +/- Ribavirin are also looking good with patients in the USA using originator V-pak/Zepatier and generic Sofosbuvir.

www.aidsmap.com/Treatment-intensificatio...atment/page/3014995/

Thank you.
Does this mean I should do an SVR24 test?