Is viral breakthrough during treatment unusual?

[prettydamscared]

Does anyone know the answer to this?  I'd like to know if there are any studies on this and/or anyone's perception of how often this happens. I've read of it happening to a few posters on this board but, for the most part, don't know a lot about it.  

Thanks in advance for any info or ideas anyone can provide.

[jmjm530]

If you want to re-cap your pre-tx stats (age, weight, geno, vl, enzymes, how long you had the virus, an acute phase or not, biopsy results, rescue drugs, tx side effects and how you're handling them, etc) plus tx history incld vl tests, dosages, hemoglobin reaction, etc. and then re-link all four studies in one thread, I'll give it an uneducated shot like I did with my own stats when I treated. But as mentioned before, the key is sitting down with a hepatologist you have confidence in who can put the academics in a clinical perspective.

That said, when it came time for me to make a decison regarding tx length, I presented my doc with the Drusano data but he urged me to treat 48 weeks beyond non-detctible  verus 36 per Drusano -- based on my age (58) and histology (stage 3). Of course both my NP and another two consultants thought 36 weeks would be fine for 48 weeks total. (I ended adding 48 weeks for 54 total and now wonder based on more recent studies if 24 weeks would have been sufficient based on my RVR).  So much for clarity in these decisions :)

-- Jim

[sfbaygirl]

Yep, if I'm out the big bucks to go to the appt. I might as well spend a few extras and get all the studies. I have Berg. Saved me a few dimes from Friole...LOL  

Yes, I do understand what you are saying about the intent to treat  skewing down the SVR rates, except wouldn't they skew them upwards if these were included? Maybe, I'll have to read that Pearlman study again...maybe I mixed that up. Hey, you didn't answer me about what you would do. Don't want to put you on the spot and I promise I won't follow you like the pied piper...just like some different points of view. Those studies sure do seem like a no brainer though....Even John is wrapping his head around this one.

[jmjm530]

I know you don't like spending the big bucks LOL but since you asked...

If it were me, I'd order up full-text for the Pearlman study you mentioned, the Ferenci study I linked to in the same post, and maybe Berg and the Tapias study Dr. J discussed with NY girl.

If you want to save some money :) then maybe just print out the abstracts for Berg and Tapias which I believe are older.  

Then, I'd study them up as best you can with special attention to how your viral response matches the study definiton of viral response -- then bring them all with you to Goofy's doctor -- he has a good reputation (the doctor not goofy :) -- and he should be familiar with all the studies and hopefully will be able to put them in proper context per your own individual stats and treatment response.

I'd be  curious on the doctor's take on the Berg statistics in light of both the fixed-dose riba as well as their "intent to treat" data which should skew down the SVR data.  

Hope this makes sense.

Jim

[sfbaygirl]

The Pearlman study is the one posted by Valtod from the AASLD. It talks about weight based Riba, high risk groups and good pecentages of SVR for 72 weeks. Would you extend to 72 weeks with a kp? 6.1? I got an appt. with Goof's doc for the 18th of Dec. I am happy about this! I want to make a decision based on several opinions, including those of you who have extended. Thanks!

[jmjm530]

Not sure which is the "Pearlman" study, but if Berg uses fixed dose riba (800mg) I don't think the results translates to those of us who do weight-based riba. Before making any tx decisions, always best to order the full-text version of a study and go over with your doctor. Besides understanding the study, harder still is to put the study in a context to make tx decisions. I find the Clinical Options -- and similar sites -- helpful in this regard as the studies are filtered through some very good clinicians such as Dieterich, Jensen and others.

-- Jim

[sfbaygirl]

Do you think this Perlman et al. study is more important for those  of us that do weight based Riba and are hard to tx? Granted it is a small study...

[Rastiss]

Viral breakthrough isn't all that unusual.  If you're talking about HCV, the treatment is only about 50% effective to eliminate the virus to the point of a SVR.  All those who are on the bad side of the 50% either 1) didn't respond at all, 2) responded but slowly and removed from treatment or 3) were UND at some point but the virus came back.  UND just means that the viral level is below the detection limit of the test - it doesn't mean that the virus is gone.

[jmjm530]

Would following protocol be as specific as full dose compliance, i.e. no dose reductions, or do they have some leeway here. The first question my consulting hep doctor asked was what dose of riba was I taking, any riba reductions and any missed shots. Obviously, he was heavily factoring in compliance before he suggested how long to treat and what my chances of SVR were.

[Hepatitis Researcher]

"Intent to treat" analysis is one in which you include everyone who started treatment, but stopped, disappeared etc.  

"Per protocol" analysis includes only such patients which followed the protocol all the way through...

[sfbaygirl]

Oh, I know I am already disturbed by the way my doc read my 10 week PCR as UND. Now I don't know... I think some writers write in a confused way possibly because they themselves don't understand what they are writing.

[jmjm530]

I think it's just bad writing perpetuated by a system that doesn't penalize it. One day they should do a study on how good (or bad) doctors interpret studies. I think the results would be disturbing.

[jmjm530]

The "Berg" figures get tossed around a lot, but seemingly not that relevant for those of us who actually follow protocol. Also, the fact that Berg used fixed dose riba (800 mg) seems to get lost when we compare out own treatment response which in almost all cases is weight-based riba for geno 1's. Again, careful reading and analysis of the studies seems to be very key. Thanks for putting at least this aspect into perspective.

-- Jim

[sfbaygirl]

Thanks HR! I never would have guessed that Intent to treat would mean people that stopped tx. Good to have someone around that knows the lingo.

[APKhaos]

In the VX case, the pathway gets the VX molecule locked onto the viron during replication. Virus with the VX inhibitor cannot replicate [or so the theory goes]. VX is a finely pointed spear.

If/when mutations lead to virons that are resistant to the VX molecule, the Inf and Riba are there to sweep them up. Seems that the current expectation is that VX will need to be given in a combo with Inf and maybe Riba to provide the broad sweep up of mutations.

The Prove 2 trial is without Riba. If that shows strong results, then maybe a combo VX & Inf is possible. Its conjecture until the data is available, but a combo without Riba would be a life changer for many treaters.

[sfbaygirl]

Does anyone see my post above? I posted a while ago and I see my name, but not the post. Weird?

I guess I will say it again...My understanding is that if you have an UND at say 12 weeks, and 24 weeks and then a positive VL at 36 weeks you have had a viral breakthough. When you never have an UND you are a non responder.

[chcnme]

Thanks APK.  Yeah that's it!  In a nutshell, or at least how I've understood it (just couldn't remember how to say all of that :)  And on the polymerase end (the poly inhibitors like HCV 796), I think I'm understanding it's doing somewhat the same thing as the protease inhibitors (VX) except it's interfering with the polyermase ...something or another...with the replication, and ... (I'll leave it at that since beyond that point it's too easy to tell I flunked molecular science.)  But yeah, that's it!  Thanks for the explanation.  

I'd read where there is no riba being given in the study (or in some arms) but I've not understood all the arms or the SOC.  I hope you're fortunate enough to be taking no riba at this point! I knew they were projecting the possible exclusion of Riba, which would be fantastic indeed since it's the riba that seems to be so bad for some.

lol sfbgirl. You aren't dreaming or hallucinating, or - if you are - I am too.  I see notes, and then I don't, or I don't see them and suddenly I do. I think it might have something to do with cookies, but I flunked computer too.  I think we should just eat chocolate chip cookies. Yeah :)  

But what you said about UND and no response, yeah - that's what I understand about it, too.

[sfbaygirl]

My understanding is someone who does not get to UND at any point in tx is a non responder or slow responder. Someone who has had an UND at 12 and 24 and then has a VL then has a viral breakthrough.

[sfbaygirl]

What's interesting in this study by Perlman, is that they used difficult to treat geno 1's, African Americans, High fibrosis, etc. They all were given weight based Ribavarin, unlike Berg (800). But it is a small study and needs to have a larger group. Quite a big difference in SVR rates with extending to 72 weeks.

[Valtod]

So does anyone else see something fundamentally wrong with the AASLD research I quoted above?

You have a group of patients ALL undetectable at 24 week. But then 67%(!) of them become detectable at week 48. How is this possible?! Mass viral breakthrough?

Or am I reading the research wrong?

[sfbaygirl]

Could this be because they were detectable at week 12? This is why the odds are so much better for 72 weeks. Who wrote this?

[chcnme]

I don't know how rare it is.   I thought viral breakthrough was any increase in the viral activity  (viral load) at any time during treatment.  I've always thought that to lower the incidence of "viral breakthrough" was the goal of therapy and future therapies (and that that was the reason VX-950 needs help with Peg/Rib). Wasn't it the addition of Ribavirin that helped reduced the incidence of viral breakthrough and that without Ribavirin there is "breakthrough"?  

[Valtod]

sfbaygirl, it's from the last AASLD.
http://www.natap.org/2006/AASLD/AASLD_32.htm
http://www.hivandhepatitis.com/2006icr/aasld/docs/110306_f.html

Yes, all of them were slow responders. But all of them were UND at  24 weeks. Then they were full-time on TX in the next 24 weeks. So how is it possible that WHILE on TX, 67% become dectable again?

CitizenSmith, interesting suggestion that 'end of TX' my mean '6 months post TX'. But in all the research I read (and it is a lot) 'end-of-treatment' means exactly as it sounds: the time when you stop taking the treatment drugs. On the other hand, '6 months post TX' is the accepted time period for claiming SVR.

And I agree that this paper is as clear as mud.

[sfbaygirl]

I think this is a similar study to BERG. It shows that extending tx to 72 weeks improves chances of SVR in slow responders. I haven't read the whole thing yet, but I know that depending on when how low your VL >6000 by 12 weeks, you have a good chance of SVR within the numbers you stated. 57% at 72 weeks and 32% at 48 weeks. I believe BERG says it's about a 25% increase going 72 weeks. I am grappling with this right now ;(

[sfbaygirl]

That second paragraph seems to be confused... The Perlman study above in Valtods post, has different numbers than this one, but are hard to tx... A 40% difference from 37% to 77% makes it really a no brainer to me...YUCK, but good to know. Of course ins. co's aren't up on these studies and neither are most dr's.