Anyone Got A "Typical" Viral Load Drop Graph?

[RobertBeWell]

I sat down with the research doctor today at my study visit, because I wanted to discuss with him his feelings on whether or not I should continue on. Though he couldn't come right out and say it, he absolutely didn't disagree when I told him that based on my results, I was not getting the study drug.

Anyhow... he told me that as time goes on, and the viral load drops, the remaining virus are "harder" to kill, because they are "tougher". In other words, in patients that respond to treatment, they usually expect to see large viral drops initially, followed by progressively smaller and smaller drops until UND.

I was a bit skeptical, but I didn't let on because I didn't want to insult the man, as he's pretty respected in his field as a researcher.

How can one virion be any harder to kill than another.

Anyone got a link to a graph of a "typical" viral load drop in a "good response" scenario?

Thanks

RBW

[Trish77]

Robert, I buy this.  My viral load dropped pretty well on my trial.  I was getting tested weekly at Week 1, 2, 3 and was well on my way to RVR based on how things were going.  When got the results of my Week 4 PCR, was kind of shocked to see I'd only dropped 627 virons from the last test after dropping in the tens and hundreds of thousands at each test - had dropped from 2.1mil from baseline and did NOT get my RVR after all.  I was UND by the next PCR at Week 6. For what it's worth, I do think the last ones hanging on are feisty little buggers who have managed to hang in there and survive and aren't going down without a fight.  Not the first time I've seen that.  

[Trinity4]

I think in a nutshell as the immune system attacks the virus mutates and that's how it survives.  Even with the initial shock and awe approach from treatment they're tricky little b-a-s-tards and become more resilient, hence harder to kill.  

[desrt]

No graphs of "viral load drop in a "good response" scenario" and don't know if there is such a thing as "typical", but willing as some graphs comparing viral load drop in a 'sucky case scenario', comparing Pegasys to Peg-Intron in two HCV/HIV co-infected patients.

http://www.medhelp.org/user_photos/show/168497

[willbb]

mutant talking mutants    LOL!!!!

[desrt]

Oops, just read the fine print. It does say "typical" on those graphs.

[spectda]

"In other words, in patients that respond to treatment, they usually expect to see large viral drops initially, followed by progressively smaller and smaller drops until UND. "

Although I was not on soc alone, this was definitely the case for me. I think it is the case for most people who become und as your doctor mentioned. Even with the boceprevir I stalled at week 6 (vl 246) week 8 (vl 274) the und at week 10.

I guess you should have your week 16 results soon. You have a lot of people rooting for you robert.

Good Luck,
Dave

[uncledudeness]

could it be that as the viral load drops, detection of the remaining virus is somewhat skewed, as a result of the sensitivity of the test procedure.

it seems that it would be harder to detect a smaller amount than when the viral load is in the millions. just a guess.

[blondie717]

I dont know that awnser for you Robert, but yes you are rooting for you!!!!!Go Robert, Go Will, Gooo Everyone Else too. Gooo MEEE. I think Ill put all us heppies on the prayer list.  Does your study doc think you should continue???

[merryBe]

So sorry to hear this Robert, I don't understand at all why they even have to have a placebo arm anymore...they know in spades what the results and stats will be there s why not give everyone at least some sort of shot at something better. Sigh, I'm so sorry. But look,no offense, but it sounds like over simplifyication, talking down to you really....stronger virons hardly covers it, but it may be all some patients need to know is probably what that guy was thinking. No mention of wild strains, no mention of mutation/adaptation, no explaination of subtypes or of the window within which the virons mutate?  (48-72 hrs.) Since you are the curious type he could have tried a little harder.
Basically, the virons that survive the onslaught of SOC are mutants of your original...were they the same, they would succomb to what their brethren succombed to, namely SOC, but they adapt and live on. That's why now there are so many subtypes within each genotype.
That's why the newer treatments are gearing towards throwing 3 or 4 things at the virus at once, so they won't have any way to turn, no way to adapt, every exit blocked so to speak, cutting off the chief pathways where adaptation is known to occur. That's why they have drugs to eat up the virus (INF) or interupt transcription or inhibit protease, etc.

If you are content with your odds without having been given the trial drug, then it might be worth going on, but if you understand what may have happened well, you might want to think about it. A good person that might be willing to eplain this to you better in here is Willing.
.
Now I understand that UND is not virus free, that the real key is getting every last viron before any mutate. That unless you have a test that goes to>zero, you may have a few lingering mutants that have adapted to the tx and will reemerge from their meager numbers once tx is discontinued.
I don' t know what stage/grade you are, but unless you are late stage why beat yourself up when treatments taking half the time with much higher rates of success are so near.
When I was having trouble getting UND some folks tried to inform me that the longer it takes to get UND the less chance current SOC will kill the dragon was...but I was late stage and reluctant to accept that even though they were very well informed.
I'm not sure 2 years on all the cocktail gave my liver the greatest rest..I'm still taking drugs to correct issues that arose due to the tx.    Remind me, what study are you in please?

[Trish77]

"I think in a nutshell as the immune system attacks the virus mutates and that's how it survives.  Even with the initial shock and awe approach from treatment they're tricky little b-a-s-tards and become more resilient, hence harder to kill.  "

This isn't true in general.  Only with the PI's have we had issues of treatment drugs causing resistance profiles to emerge in virons that remain.  Treatment with interferon and ribavirin does not create resistance to these drugs in an virons that remain.

[Trish77]

Robert, I think if you asked any of us to post the "graph" of our own viral decline, it would potentially be alot up front and then less as it goes towards UND.  It was for me.  What really matters is your own viral decline and results at certain milestones for YOU.  The milestones are generally agreed upon with regards to decisionmaking.  It's when we're in that border area that it gets tricky and decision-making gets more angst-filled.  Thinking of you.  

Trish

[willing]

take a look at figs 3-7 of Filipowicz'10 (free access):
http://www.ncbi.nlm.nih.gov/pubmed/21079746
these are the results of a recent clinical trial testing the effect of SAMe among previous non-responders (courtesy of CS).

Fig 3 remained NRs, Fig 4 are RVrs, Fig 5 cEVRs, Fig 6 EVRs in new tx and Fig 7 EVRs in previous and new tx.

This was a tough crowd (non-responders, many F3/F4s, two liver transplants during the trial) and the SVR results are not that great ( eg out of four cEVRs only one SVR ) so I wouldn't consider these "typical" results nevertheless there's lots of before/after VL graphs to compare.

SAMe clearly helped VL reduction if not necessarily the final outcome.

>How can one virion be any harder to kill than another.

I think this is what your dream was about - you're   cruising along blasting away holdover virions (and Trish was just bystander collateral damage)  .

But remember that individual  virions can have *very* different sequence which gives some greater survival advantages. An easy example is virions with the right changes in their protease protein are completely immune to tela/boce (the drug won't 'stick' to their protease). An older and subtler example is that virions that don't include the right epitopes can avoid MHC presentation and thus CTL detection of infected cells - the immune police can't detect  infected cells. This is part of why g1  tx is so $$&%%$ long..

All the best with your w16 results ( keep those battleship guns blazing!)

[Trinity4]

Did not say resistant -  said "resilient"  Mutation DOES cause resistance

Basically said the same thing MB did only short form don't ya think?

[RobertBeWell]

Thank you for the many kind words, and all the material to digest. I guess I never really thought about how the virus is actually eliminated from the blood stream graphically, but it makes more sense now.

Several asked what the doctors opinion on continuing was, so here goes:

In a nutshell, he was baffled that I thought my results were so bad, and told me that there is no way he would recommend I quit now in light of how well I had responded. Basically, he told me:

1. I had in fact responded very well, and that for all practical purposes, I was undetected. He also pointed out that we don't know if this was just a one time anomaly.

2. Since this is a study, we don't have any way of knowing my viral load profile, but that based on the rest of my lab results, and what he has seen in is practice, he's very confident that I achieved at least a 2 log drop by no later than week 4, and perhaps even sooner. An important predictor of success is fast early response. I believe him, as this is a hepatologist who has literally treated THOUSANDS of patients with SoC - it's the main focus of his practice.

3. My genotype is C/T. While not the best, it isn't the worst either.

4. My side effects are almost non-existent.

I appreciated his time and approach - in the end, he was very clear that the decision was mine to make. I didn't feel pressured one way or another to continue.

I'm still not absolutely certain what I'm going to do, I'm going to wait a week to see my lab results. I will probably continue unless something obnoxious happens like breakthrough.

Thanks for all the clarification and support!

Robert

[Proactive]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720526/

http://www.comparative-hepatology.com/content/4/1/9

[Trish77]

"I think in a nutshell as the immune system attacks the virus mutates and that's how it survives.  Even with the initial shock and awe approach from treatment they're tricky little b-a-s-tards and become more resilient, hence harder to kill.   "

"Did not say resistant -  said "resilient"  Mutation DOES cause resistance

Basically said the same thing MB did only short form don't ya think? "

What you said was that the virus mutates as the immune system attacks and that they become more resilient.  

I'll repeat - in general, this is patently untrue.  Some virons are simply tougher than others, need different weapons, etc.  They do NOT mutate in general aside from PI'.s  As a general rule of thumb, they do NOT become more "resilient" either which means they become more resistant.  This does NOT happen due to treatment with interferon and ribavirin.  That they become more resilient is incorrect. Some virons simply ARE more resilient...or rather respond differently to various elements.

Virons do not become stronger as a result of interferon and ribavirin causing them to flex their muscle and therefore become more "resilient" as you put it.  They are what they are and some require different weapons to fight them - hence why we might introduce Alinia, Vitamin D or whatever we can think of that might add some extra killing power since interferon and ribavirin can be insufficient on their own, which is why we're not seeing 100% SVR rates from using them.

Willing's post explains this and sums it up rather well.  

[spectda]

"I think this is what your dream was about - you're   cruising along blasting away holdover virions (and Trish was just bystander collateral damage)."

I think willing nailed your dream robert, haha. Be careful trish!


"keep those battleship guns blazing!"  My new theme for completing treatment,

[Trinity4]

And I'll repeat you're wrong -  the virons do mutate and learn how to avoid the onslaught of the immune system because they have changed what the immune systems recognized as an intruder. Do you see stronger in my reply?  Do you see ineffective to SOC?  Please provide data that verifies "They do NOT mutate in general aside from PI'.s".

[Proactive]

to the orginal question
"Anyone got a link to a graph of a "typical" viral load drop in a "good response" scenario?"
http://www.comparative-hepatology.com/content/4/1/9/figure/F1

[Bali05]

I like what my renowned Hepatologist had to say.
After all the trials and tribulations I had pre tx ect.. then when I finally got my first UND
I asked him , so what exactly is happening in my body now with this virus that
we can not find any more ?

His answer was  "we simply do not know."

[RobertBeWell]

Another point the doctor made was that there is really, truly no way to measure being absolutely virus-free (at least not in common research practice), because even the most sensitive assays commonly in use have a detection limit of about 2 IU/ml - and that is under theoretically perfect conditions - sample is perfect, properly handled, the machine is perfectly calibrated and operates perfectly, etc.

That is why they treat for soooooo long on SoC - it's really a brute force approach - to try and get rid of every last virion they possibly can - i.e., all those little buggers that comprise <43 or, in my case, <25, or in the case of UND - those that remain below the limit of detection.

Good call on the "battleship dream" :-0 believe me, I'm blazing away with all I got. Here's to hoping we sank another 15 or 20 of them since Week 12.

[spectda]

The uproar about the PIs and variants is that they may become dominant, and can be very long lasting (two years with tela and boce) making it difficult to retreat with the same type of Direct anti viral. Also I believe there is concern that people with the variants from the PIs may infect other people and create new resistant strains in the general population. With soc I believe they quickly return to wild type virus after the treatment is stopped enabling people to retreat with riba and ifn.

http://www.hcvadvocate.org/hepatitis/Basics/New%20Antivirals_10.pdf

Viruses use various pieces of the host cell’s genetic material in order to reproduce, or make more copies of itself. Viruses survive because of their ability to constantly adapt and
change when they are under attack from the immune system. Viruses still try to reproduce even while under attack. In a hurry to escape, a virus may make a bad copy
of itself, which slightly alters its genetic make-up. The process of change actually produces a variation in the virus, known as a mutation or quasi-species.

HCV acts like this. When you are newly infected, your immune system recognizes that an uninvited intruder (HCV) is in your body. Your immune system alerts your body to destroy HCV. However, HCV hurries to escape and makes a sloppy copy of itself, which outwits your immune system.

Your immune system is patrolling for the original intruder, not realizing that the virus now looks a bit different. Now HCV can multiply at a faster rate.Eventually your immune system catches on and looks for the bad copy. In a hurry, HCV mutates again. This process may cycle through many, many mutations."

[Trinity4]

Well said Specta, exactly my point.

[nygirl7]

Exactly right Spectda this is a well known fact that we have always discussed as being why we want to get to UND as quickly as possible and why the first time you treat you have the best chance of succes - before too many mutations arise. That is even with SOC as most of us did not have  PI in the mix nor was any of this known yet about PIs.