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

[eureka254]

"Are they interspersed among UNDs? My solution to the blip problem is to make like an ostrich - I'm going to put off further testing until it comes time to add a PI. The results would change nothing but maybe add stress, ditto an il28b.

Yes, the blips were spread out (about a two month gap between each if memory serves me correctly)... and I actually like your ostrich trick... less extraneous data can make for better focus.  

"Sequencing  soc-recalcitrant virus is unfortunately a long ways off from being clinically useful. "

I realize it would have little clinical application to test "breakthrough" virions, but my academic curiosity makes me wonder if still sequencing detectable RNA post long term SOC exposure might later provide some clues towards the development of the perfect cocktail or immunization.  Ah, dreams, dreams...

[willing]

Eureka: well that und5 at w13 seems  confirmation that the decline held at a  steady rate of 0.5/wk, give or take a few days.  A VL curve that doesn't flatten is a good VL curve in my book. The 'blips' are not great news but if there's no steady rise your Dr's hesitancy to say breakthrough seems on point. Are they interspersed among UNDs? My solution to the blip problem is to make like an ostrich - I'm going to put off further testing until it comes time to add a PI. The results would change nothing but maybe add stress, ditto an il28b.
Sequencing  soc-recalcitrant virus is unfortunately a long ways off from being clinically useful. It would be a bit like trying to sort out the plot of a movie by studying the 1s and 0s on the CD - noone  has  a clue how to read the story  yet. For PIs on the other hand it comes down    to watching  for changes in a few amino acids in the neighborhood of the drug binding  site - much easier.

Trin: agreed - the virus mutates 24/7 regardless of what we're throwing at it (if anything). The word 'mutation' has an ominous sound to it, maybe because of the association with cancer in human dna, but only seems to have started coming up in posts here since discussion of PIs.

Trish: there seems to be a bit of contradiction between the results Trin posted and standard practice. On one hand it's well accepted that there is no such as soc resistance and if one fails it's perfectly reasonable to try again. On the other that study suggests that if one's tx is reasonably successful there is a great narrowing of sequence diversity towards the end of tx. So if you relapse or breakthrough and then jump right back in it would seem you'd be  fighting the descendants   of the soc-resistant holdovers. Maybe a good argument to give it a rest and let wild type diversity resurface before trying again (which most seem to).  

[Trish77]

That's what we do here on the forum.  We discuss things to clarify on points in an effort towards accurate representation and understanding of the information and a number of other folks made useful contributions.  I don't see where the personal insults are a positive contribution in any way - clearly you're taking this personally for some reason so I would agree on your final note  - best to leave it as a case of misperception with a little semantics thrown in.

Trish

[Trinity4]

Silly me, must be some kind of language barrier going on.  I know what said and I know what I meant.  No words like stronger, resistance to INF were said by me.

I am well aware to the PI resistance profiles and have done more research than I care think about.

In any event, this is beginning to bore me so I'll leave it as a case of misperception with a little semantics thrown in.

Trinity

[Trish77]

""They do NOT mutate in general aside from PI'.s" and that is simply not a true statement. "

You took that incorrectly, however it was also poorly worded on my part.  You suggested that the virus mutates,making it stronger and harder to kill - suggesting that treatment with ribavirin and interferon that does not result in SVR leaves behind virons who have become stronger and have developed resistance profiles.  This would be misleading to suggest that this is the case and the only reason I said anything at all - I wouldn't want people on treatment who don't acheive SVR to be concerned that now the remaining virus has gotten even stronger as a result and is even more resistant.  It is what it already was.  Tough little buggers that maybe need a different kind of firepower.  

PI's on the other hand DO develop resistance profiles that make them harder to kill with the PI drugs that that were used at the time.  They do NOT however become resistant to SOC drugs - ribavirin and interferon and in fact, these PI-mutated virons are weaker than regular virons and still susceptible to interferon and ribavirin.  So there is hope in that regard.  The difficulty comes in when using a PI and not getting SVR, that not only is there PI-mutated virons ... but ones that seem to require a different kind of firepower than interferon and ribavirin.  So developing a resistance to a PI and knowing that interferon and ribavirin didn't kill all the virons means that yet another drug on top of interferon, ribavirin and a PI with a DIFFERENT resistance profile of the one used will be required.  So it gets more complex when adding in a PI and not getting an SVR first time around.

Hopefully I chose my own words a little better that time around.

[eureka254]

Being a person of average ways and means and medians, indeed I was expecting and hoping for him just getting to undetectable at about week 12... and in fact, we did indeed request a higher sensitivity test for week 13, and it was indeed undetected <5.  However, subsequent to week 13, he had 3 detectable VLs thereafter, and those VLs were 19, 61, and 89, though his doctor has not used the term "breakthrough" because of the low levels.  From a scientific standpoint, though, I wonder if testing those detectable virions for sequences would have shed any light...