Restarting treatment earlier. Is it a mistake?

[Sally01]

Hi, I received my first UND in July and then my Peg/riba treatment was interupted off and on the next few months due to illness.  I am still receiving treatment for an opportunistic lung infection which is apparently very stuborn.  I am post transplant also so my immune system was pretty low.  Also I worked in a hospital in a highly infectious area.  Won't do that again.   Anyway I have had no treatment for the HCV since Sept.  My November VL came back UND.  I was thrilled but a little surprised
      I asked my doctors if I could start the Peg/riba again so as not to loose this opportunity to acheive SVR but they all seem to put the question off or refer it to another doctor for approval.  Final say was to come from the transplant team in Miami.  They don't see me until Dec 12th and was told to wait until I was seen.  My nurse co-ordinator is out ill and no one is responding to my plea for more immediate help.
   I feel better than I have in months.  No doctor has givin me a reason for any kind of interaction with the ribasome I am taking.  Last Wed I had blood drawn and my liver enymes had elevated from 14 to the 50's.  Scared me.  I took the peg and riba on Thanksgiving on my own.  Seemed bad to wait for appointments when the meds are in the fridge.  After about 6 hours I had a bad flu-like reaction but the next day I was better and am continuing to do well.
    Do you think I messed things up> I am planning to take it again on Thursday.  By the time my Dec 12th appointment rolls around I will have taken it 3 weeks. If I feel ok which uspectI will should I tell the

[cuteus]

how sensitive were the tests used in July and Nov?

what was your total tx time?  You have been negative for two months post  tx, and still negative.
what was your genotype again?

[Sally01]

The tests were Bayer and only down to 615 IU/ml.  I am 1a genotype.  I treated for approx 70 weeks to get my first UND in July, then had to stop treatment and Aug it came back 750,000.  Started treatment and it was UND in Sept, not tested in Oct. Became ill and had to stop treatment again but it was still UND in Nov.  I don't want to loose this opportunity especially since I have the meds.  I think the doctors are just trying to cover themselves but I don't think the virus cares much when my appointment is.  When I saw the liver enymes jump I just did it.  So far no problem.  Just don't know if owning up to it will cause a problem or maybe solve theirs.  Thank you so much for answering

[honey11]

Sally,,,sorry to hear you are having problems.  If I was you,,,I would get a PCR as soon as possible if that means having your family dr do it and if you are detectable then make your appointment next month to decide best stragedy for you go on this.  Once you have stopped the meds for a period,,,,you pretty much have to start back from square 1.  I understand what you are saying about having them in your fridge but I don't think I would take them now until you find out if you have a viral load.
Best wishes!

[desrt]

I think if you're in the middle of fighting a 'stubborn' lung infection, the doctors are doing better than "just trying to cover themselves" - sounds like they might have an honest interest in your well-being.

[Sally01]

Thanks for all response. I guess I still have time next week to decide if I will continue.  Maybe I will press to talk to my doctor again.  I just really hate to start over at this point. I have 10 more days on the ribasome and I really feel much better. I will take all you say in to consideration.  Wishing you well

[cuteus]

I had spent hours looking for a study that I had bookmark a while back and could not find it.  It dealt with controlled interruption of tx, and how subjects achieved SVR with it.  People were treated, then tx stopped for two wks and then restarted.  It allowed for the immune system to develop a way to keep hcv away.  maybe you did too.  it could be that the interruption and restart is all you needed to get svr.  I will be at work tomorrow and that is where I have that bookmark, I'll see if i can find it.  Two months off tx and you are still neg, is a good sign.  but it could come back  or it could stay down, no way of knowing unless they do better testing.

[Sally01]

Thank you so much. I'm starting to feel like maybe I jumped too fast.  I will call my ID doc tomorrow.  Maybe their is a method to this maddness.

[jmjm530]

Link below to the 2004 abstract on the "controlled interruption" approach mentioned. I found this approach very intriguing and followed up on it some earlier this year. Reliable sources then suggest that while they achieved non-detectible virus up to 4 months post controlled interruption or "pulse" therapy, all relapsed and therefore no SVRs. My understanding is that this work may still be continuing as a "missing link" may be looked for -- perhaps combing SOC pulsed therapy with a third agent such as an experimental vaccine, VX-950 or even Alinia. The last two mentioned agents just my opinion.

That said, your situation is different as your first tx didn't conform to the pulsed approach as it was much longer. Still, who knows how these things work. Fact is your non-detectible for two months and that should be encouraging. Personally, I wouldn't start taking any drugs at this point without getting your doctors onboard.

Here's the link to the abstract. Scroll down to Poster 398.
I mentioned this approach to "HR" a few weeks ago, so flagged him in case he hasn't run across this approach.

http://www.hcvadvocate.org/news/reports/AASLD_2004/Posters_AASLD_2004.htm

[jmjm530]

Just to add a little...

The approach appealed to me because of it's elegance, i.e. customizing tx duration due to immune system response. Some might require just one "pulse", someone else two pulses, other more. But no one getting more meds than they need.

Each "pulse" being the time it take to become non-detectible given I believe weekly VL tests. Then the drugs are stopped and monitoring continues until either it comes back (when the second pulse would start) or until SVR is reached.

Elegant in *theory*, yes, but since no SVRs, the pulse approach is not yet ready for prime time :)

-- Jim

[sfbaygirl]

Do you know the name of the drug that is from India that boosts the effects of interferon? I know it's not approved here, but your designer tx intrigued me....I wish the darn dr's weren't so scared to try a few off label drugs on us, especially if we are at risk of not SVR or relapse.

[cuteus]

JM
aha!  I was hoping you  had bookmark that one and were peeking in at some point.  It is funny how I come accross some of these studies, obscure ones sometimes, while looking for other stuff altogether, but when I  actually try to do a web search for it specifically it does  not come up in any of the results.  I hate search engines! I am glad you saved it at home.  I have more stuff saved at work than at home, and i end up needing them at the wrong time.  I remember the study as being one with very few subjects in it.
It seems to be an approach used mostly with HIV mono or coinfected.
thanks again

[Hepatitis Researcher]

The therapeutic approach of stopping treatment to let a newly upcoming viremia induce a stronger immune response has been used also in HIV - it was called "structured treatment interruptions" - and in HBV where they called it " in vivo therapeutic immunization". "Pulse therapy" where the retreatment was started according to a fixed schedule independent of reoccurrence of viremia, was also used. Unfortunately, none of these approaches worked as well as hoped. The main reason for this is, that in any viral disease - while the immune response is best elicited by moderate amount of viral particles - the dominant aspect is that you must never let the virus regain "genomic power" that is the capacity to adapt using massive amounts of genomes as base. You want particles as immunostimulants, but they need to be without genomes within. Here comes in the concept of therapeutic vaccination - a broad field with good efforts but little success to date, both in HBV, HIV and HCV. What mostly riles up the immune system is extrahepatic presence of virions, fully structured viral particles, not component vaccines. Intercells vaccine for HCV remains to be further evaluated....

[BThompson4]

I would definitely get a more sensitive viral load test.  I am geno 1a post transplant also, and I cannot get undetectable at less than 25 ml/iu even though I have been below 615 iu/ml for the last eight weeks:

week 10 - 1430 iu/ml
week 12 - 651  iu/ml
week 15 - 547  iu/ml
week 18 - 174  iu/ml

With the less than 615 ml/iu pcr I would think I was undetectable, and that is certainly not the case, with lots of implications for treatment length, intensity, etc.

How high was your beginning viral load?  You have a much better chance of svr if it was low at the beginning of treatment as a genotype 1a.

I think it is a good sign for you that your vl returned at a fairly small number before you went undetectable again.  Hope you beat this thing!

[jmjm530]

HR:...Here comes in the concept of therapeutic vaccination - a broad field with good efforts but little success to date, both in HBV, HIV and HCV. What mostly riles up the immune system is extrahepatic presence of virions, fully structured viral particles, not component vaccines. Intercells vaccine for HCV remains to be further evaluated....
---------------------
I think the idea was next to combine the structured treatment interruptions with the experimental vaccine, but not sure if that has been done yet. It is interesting that while no SVRs, they did achieve prolonged EOT viral negativity for up to four months, with relatively little exposure to the SOC treatment drugs. Again, maybe the experimental vaccine -- or some other third agent like VX or Alinia -- may be the missing link. Meanwhile, these short-term transitory "SVRs" might be construed as "super maintenance therapy" although no follow-up studies on liver histology I'm aware of.

[jmjm530]

In reference to RTS's post below "HR-Question about re-treatment" -- do you give any credence to his supposition that his relapse somewhere between 3 and 6 months post treatment was caused by a dental procedure? Apparently he was VL negative via Heptimax at 3-months post treatment and then positive at six months. Also, how common do you think this is? I've read recently that the 3 month post correlates very closely with the six months so this would put him in a very small group I would think.

Related -- I SVR'd as measured by Heptimax three months ago after 54 weeks of tx and an RVR (via Heptimax) at week 6. In another month or so I'm planning on having a tooth implant which of course requires surgery placing the implant device into bone or sinus. Do you think this might have any negative consequences virus-wise and would you put the procedure off?

All the best,

-- Jim

[cuteus]

Ah, the dental fear.  I went as far as to tell my dentist to make sure not to reinfect me, and asking questions as to how they sterilize their tools.  I had extensive dental work during and after tx.  Still negative by PCR.  It would have been ironic to get re infected with my own virus at his office.  It did not happen.  Ask freely about their sterelizing procedures.  I have seen receptionists handle the tools without gloves sometimes...unacceptable.

[DoubleDose]

I used to fear any chance of reinfection after getting my SVR, and went to great lengths not to reuse any old scissors, cosmetic items, workshop tools, toothbrushes, safety pins, etc.  I am not sure anymore that those things are really worthy of much concern.  From recent comments, articles, and events, I am now more concerned about HCV 're-activation' than re-infection.  I think that we need to be very wary of immuno-suppressive medications, extreme immune system events (someone who does a binge drinking celebration after SVR, or becomes very ill from some other cause, etc), and anything that might be able to allow any remaining virus that is in 'remission' or 'in-check' phase to re-emerge or cross this 'barrier' known as SVR.  I am beginning to really believe that this is an actual possibility, even though the percentages are probably very, very low.  If it does work this way, there are probably a handful of things that all of us will want to absolutely avoid throughout our future lives.

DoubleDose

[jmjm530]

My concern with the dental procedure is not reinfection, but reactivation as suggested by RTSs thread where he relapsed somewhere between the 3 and 6 month post treatment point and mentioned his dental work as a possible cause.

[Hepatitis Researcher]

The tooth implant or any surgery exerts some stress on the body with temporary reduction in immune effectiveness.
In the future we might have temporary no sides HCV shielding drugs for such occasions. You could even now use a 20% Pagasys dose in and around that time to be really safe.

But if you fear reinfection from an external source - your chances should be about the same as for anyone in these procedures. If no vaccine will be found, there will be 20 Million HCV cases in the USA by 2018 or so....
Chances are obviously still quite small and it probably is better not to be overrestrictive- do what really needs to be done, but dont tatoo  " I beat HCV"....

[jmjm530]

Sometimes being cautious isn't being logical. Logically, I don't think I have anything to worry about with dental work, whatever, as studies suggest the durability of SVR. It just seems that the durability climbs from around 98-99% to close to 100% as you become non-detectible one year post treatment. As to HCV coming back after "some years" I only know of one or two documented cases, so one really has to be suspicious of what one hears in this regard. What double dose and others are talking about is altogether different. They're talking about "persistent" virus meaning it's non-detectible in your blood but seemingly present in tissues and the lymphatic system. So far there are proven clinical consequences for the persistent virus and for all we know it may be totally benign. Time will tell.

[jmjm530]

No fear of reinfection, the question only related to "reactivation" of virus due to what you term reduction in immune effectiveness. Specfically, would you recommend the surgery now (I'm 9 months non-detectible since stopping the treatment drugs) or would you wait until after the one year mark. Taking any type of interferon drug prophalacitvely is not an option I would even consider. The second part of that question is have you ever heard of an actual relapse after SVR for something like a dental procedure or simple operation. Thanks.

-- Jim

[jmjm530]

The reason for the second part of the question is that I assume a certain proportion of SVRs have dental work in the year following treatment and yet we all know the HCV durability studies. I'm not trying to answer my own question -- or perhaps I am :) -- but simply concerned because of RTSs relapse with a dental procedure mentioned as a possible cause. So on one hand I don't believe there's a problem, but on the other I'd like as much info as possible. I understand the theory behind reactivation, but if indeed documented cases are either non-existent or rare, doesn't that shoot holes in the theory?

[jmjm530]

Child:Jim, I am not on the right path here? having "persistant"
virus in tissues and such after being non-detectable then comes back right? 3- 6 mo right?

If something comes along like surgery or such would that not reactivate the virus,even if undec. for a year or so, if it is like hiding somewhere?
-------------------------------------------------------
That's the theory but IMO it has to be balanced by the incredible sparcity of relapses after six months -- and especially one year post treatment. If no one is really relapsing -- as defined as detectible HCV RNA in serum -- then where is the reactivation? I believe there are one or two documented cases but IMO that's too small a number to draw firm conclusions from.

-- Jim

[DoubleDose]

Jim, you said:
As to HCV coming back after "some years" I only know of one or two documented cases, so one really has to be suspicious of what one hears in this regard. What double dose and others are talking about is altogether different. They're talking about "persistent" virus meaning it's non-detectible in your blood but seemingly present in tissues and the lymphatic system. So far there are proven clinical consequences for the persistent virus and for all we know it may be totally benign. Time will tell.


My reply:

No, what I am talking about with the virus coming back after years of SVR (in the immunosuppressed cases), has everything to do with 'persistent HCV after SVR'.  This persistent virus after SVR may be the 'remission' form of the virus, which is now being held in check by the immune system.  If an extreme shock to the immune system takes place, thus effectively shutting it down for a period of time, the virus might then re-activate, and begin to reproduce beyond the control of the immune system, thus being 'reactivated' and becoming the chronic, active HCV infection that we all are very familiar with.

My conjecture is that the 'persistent virus' is exactly what causes those cases of rare relapse. Similarly, the people who have 'spontaneously cleared' the HCV virus, by the way, also seem to have the same evidence of 'persistent HCV' in their bodies in various tissues, etc. (and similar symptoms) These people would also be at risk for a 'reactivation' of the chronic infection if they became immuno-compromised, but again, since they cleared it initially years before, they might just clear it again.  Those who got their SVR from combo medications would probably not be so lucky.

I just wanted to clarify my prior comments.

DoubleDose