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

[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

[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?

[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!)

[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

[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.

[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?