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Meds, Mind, Body & Benefits => Questions About Treatment & Side Effects => Topic started by: thor on December 12, 2010, 12:39:51 pm

Title: Atripla Regimen Failure...or Temporary Blip?
Post by: thor on December 12, 2010, 12:39:51 pm
Hello everyone,

This is my first posting here. Thank you to everyone for sharing your thoughts.

I tested positive in August of 2009 and have been on Atripla since December 2009. As of May 2010, my VL was undetectable, but my last few lab results from July, October, and December have shown elevated results (95, 1050, and 396 respectively). My CD4 count has continued to rise all year from 360 in September 2009 to 560 in October 2010, my adherence I'm fairly certain has been 100% (I use a pill counter each week and have standard sleeping habits), and my drug resistance genotype test as of last year revealed no viral mutations. My doctor also ordered a genotype resistance test in April and in October, but neither one came back with results due to "failure to amplify the virus" (indicating <1000 VL).

My doctor called me on Friday to give me the results of my latest labs and advised me to switch from Atripla to Reyataz-Norvir-Truvada. He tells me that he suspects there may be early Sustiva resistance developing or that my body may not be adequately processing Atripla to fully suppress VL, and he worries that I could develop further drug resistance with low-level viremia.

I'm however a bit resistant to make the change given my difficult experiences adjusting to Atripla side effects last December (now fully under control), my 100% adherence to Atripla, and the lack of conclusive drug resistance. I also wonder if concurrent cold and respiratory infections at the time of my tests in July and October may have affected my VL levels, and that the December result could have been compromised by a flu shot I received on November 10th and a terrible respiratory infection that knocked me out over the Thanksgiving period. I've also been training for my first marathon since July and though my doctor tells me there is no hard medical evidence that endurance training affects VL levels, I wonder if this may be an under-theorized area of HIV treatment, given all the runner's literature I've been reading about depressed immune function for up to a week after long training runs.

So, I'm considering asking my doctor to consider two options: 1.) continue on Atripla for another month and be re-tested in early January, by which time any flu shot, respiratory infection, or marathon training effects will have subsided (I ran the marathon last Sunday, the 5th), or 2.) undergo a controlled "treatment interruption" (starting with a 10-14 day course of Truvada to protect the Sustiva) for a month, after which my VL rises above 1000 and I do a successful genotype test, which will definitively confirm if Sustiva resistance is or is not occurring.

Any thoughts on this situation? I feel like it's a fairly unusual set of circumstances and I'm reluctant to make a jump into a new set of meds - and deal with the potentially frustrating new side effects of Reyataz-Norvir - without having further information about what is actually occurring.

Thank you for your help!
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: eric48 on December 12, 2010, 07:02:16 pm
Hi,

this is a bit unusual and, you are correct, one needs to allow at least some time to reflect on these numbers and what they mean to you in terms of decision making.

Your are very right to ask in this forum: it is active and pro active.

And remember : YOU are the decider

Eric
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: mecch on December 12, 2010, 07:11:27 pm
Switch. your doctor gave you some good reasons.  Getting used to your first regimen included getting used to HAART, period, no matter the combo.  A switch will probably be unnoticeable.
I doubt you will have a hard time on the next one and it may control your viral load. There are enough combos out there and a lot of them are easy enough to deal with and I think doctors nowadays really want to see patients stay undetectable.
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: Inchlingblue on December 13, 2010, 09:26:56 am
I'd ask Dr. Gallant what he thinks:

http://www.hopkins-aids.edu/q_a/index.html?categoryId=9352&siteId=7151
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: wtfimpoz on December 13, 2010, 11:02:33 am
This is a recurring issue I've observed with Atripla, both on this site and others. 
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: leatherman on December 13, 2010, 11:46:13 am
You've been a year on this med, you've only been UD once, ans you have multiple tests showing a trend of not being UD? I'd consider the switch as obviously the Atripla regimen doesn't seem to be as effective as would be liked.
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: newt on December 13, 2010, 01:39:36 pm
Hello

Either you can switch to Reyataz (tho personally I rate Prezista as better option PI wise these days) or wait a month. I wouldn't do the treatment break, it may not give up enough  of the apparently resistant mutation to discover it in a test, given that you will still be on Truvada and not on efavirenz, and efavirenz is needed to select for the resistant mutation, plus this has a risk of encouraging resistance to the two drugs in Truvada.

Your 95/1050 results are compatible with a viral load of around 300 on average. Perhaps you just need more time. Your initial response was good, textbook even. But you don't wanna wait too long with a viral load between 50-500. Undetected minority resistant populations of HIV only come to the fore on treatment, and this might explain the stubborn last few copies that won't drop off your viral load.

I am sure your doc has seen this often before, hence the encouragement to switch now.

That the lab couldn't do a resistance test suggests your viral load is lower rather than higher. A viral load of 500+ should be adequate for modern resistance tests.

There is no right or wrong answer here. There's not enough information. It's your call.

- matt
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: eric48 on December 13, 2010, 04:20:21 pm
Hi,

here again, matt gave you some enlightening comments, while I was writing mine, he is a bit faster than I.

Let me provide you were I was at (before matt's post, that is) :

 A discussion like this one is very difficult and I have had bad experience on this forum trying to explore the non-obvious.

The obvious is : resistance. Please kindly mark my words, that I would list resistance as the most obvious likely culprit. (so that I do not get labelled as a resistance denyist...)

Say, for the sake of example, that it is NOT resistance (and I am NOT  saying that is is NOT). Then what else could it be ?

Atripla, had until recently been working for you. Replication had been halted.

VL has decayed

There is a fast initial decay (phase 1)
then a second phase 2 where the remaining, previously infected CD4 , die, releasing there viral load
Once phase 2 is over, and provided the meds works on you and your virus, you are expected to become UD
Since you have become UD (twice). this phase 2 is over.

There is a phase 3. Some CD4 enter a latent state, like they are enkysted. From time to time a latently infected CD4 will die, releasing a tiny bit of VL, still below the level of detection.
That pool of latent CD4 will decrease very slowly with time but will NEVER disappear. The reservoir may likely reduce in size with time, we do not really know. They are not yet fully identified and quantified.

If for some reason, a good number of CD4 suddenly wake up and subsequently die, these latent CD4, one suspected reservoir, release some VL.

A good reason, for them to wake up is obviously an infection (acute or weakened like a vaccine, or both) (it is a possibility that a raise in CD8 percentage be a marker for that infection, so have a look at your CD8 percentage curve)

Your raise in VL is, apparently , say, high. It also has a wave shape, up then down.
It is also, on the timeline, very close to the end of phase 2... Your 'reservoirs' have had no time for their slow, yet incomplete decay.

So, while the resistance theory is the most likely and, also, the most potentially dangerous, the blip hypothesis is not that stupid...

One , technically feasible way to rule out one or the other is a resistance test on your 10/10 blood draw: VL 1050...

Here, it depends on resistance test availability / cost and lab policy with regards to keeping blood sample.

I , for one, got a resistance test at VL 700, costed me $ 1000 and was done on a 2 month old sample.

Because a resistance test is costly and time consuming (say 3 weeks), if you are to ask your doc to stay course for, say, an other month (and I am NOT saying that you should, that decision is up to you)
but is you were to go in that direction and if the resistance test is doable (availability, insurance coverage, your own $$, what have you), then I would advise that you initiate that process real quick.

So that if you are to stay course for a month, in a month time you will have in hands both: your new VL in one month AND the resistance test results.

It is like a bet with a coin: one side is resistance (and if it is PIs will most likely be strong enough to stamp it out, even if you start in one month)
the other side is blip and here again , one month may be an acceptable waiting period, but resistance is a matter that should not be taken lightly.

It is all up to you, but during this next month period, you can still explore the 2 sides of the coin. Also, discussion with your doctor is most likely to be tough. Get your homework done...

Here again, this is not any advise I make (needless to say, certainly NOT a medical advise), YOU are the decider, and as such, have to be thorough in the routes that you are exploring.

Cheers

Eric
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: newt on December 13, 2010, 05:56:37 pm
Guidelines, for good reason, indicate peripheral blood viral load being over 50 copies per mL when on treatment is a caution note for changing treatment since it may lead to resistance.

A blip is a one-off test over 50 copies in a trend of results that is generally showing a viral load of 50 or less.

Viral decay is difficult theoretical science, and probably beside the point in clinical care. Replication had not been halted in the OP's case, since he has several viral load tests indicating a viral load in the 100s. The difference in quantity between a viral load of 50 and 500 is the same as between 50,000 and 500,000, ie 1 log of virus. This is clinically important.
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: eric48 on December 13, 2010, 07:19:32 pm
The OP 's question is clear, simple and right enough:

Atripla Regimen Failure...or Temporary Blip?

It is either one or the other (unless there is a third theory around ??)

If it is not one then it is the other and vice versa.

If it is a blip, the VL next month should prove it (and it takes one month)

If it is resistance, the resistance test on his october blood sample should prove it (and it also takes one month)

whichever side of the coin it is, he'd better get his homework ready for next doctor's visit.

In a recent discussion with my own doc, I commented that I was happy I had followed his advice (on the choice of combo).

Although he was flattered, he also kindly reminded me that I had, at that time, the entire liberty to refute/refuse.

After all, one is still free to get the prescription filled and throw the meds in the sink (not that I would advocate that though...by far)

It remains HIS choice.

When I was under the 'threat' of a possible regiment change, I had also made sure that I had my prescription refilled beforehand and checked my 2 months advance stock.

If not in aggreement with doc, one ultimatly remains the decider.

Not that it is an easy bet for the OP to make...

But if he is in the forum, it is most likely because he had already played the Russian roulette in the past

As you kindly reminded him: it is his call...

Time to go to sleep (here)

Enjoyable discussion...

Eric
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: Assurbanipal on December 13, 2010, 07:44:12 pm
In your shoes (but on a different regimen and with a little lower viral load) I would switch.

In fact, I did switch. 

Last year.

There's a thread in this forum about it if you search for "blip"

 :)



And, as Newt pointed out, "blip" turns out to be a technical term in the literature about HIV treatment.  It is defined as a detectable viral load that is bookmarked by undetectable viral load measurements.  What you are experiencing is not what would be referred to as a "blip" -- instead it is referred to as "low level viremia"

There is apparently no agreement amongst the doctors on what to do when one shows up with low level viremia.   Some switch, some don't.   (At least, that is what the US treatment guidelines say)

So, it is one of those areas where the answer is not obvious.  But, given it is your first regimen and there are many other (easier) ones out there... I'd switch.

Welcome to the forums ... and let us know how things go.


Assurbanipal
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: eric48 on December 13, 2010, 11:33:56 pm
hi Assurb,

I though you had written somwhere that you had switch not due to VL but to SE... Maybe I got it wrong

Have a good one eric
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: thor on December 14, 2010, 10:24:45 am
Thank you so much everyone!

I'm in the middle of studying for finals here, so have been putting off making a decision for another few days. But my plan now is to have a longer phone conversation with my doctor on Thursday or Friday about my options. I'm feeling a LOT more empowered to make my own decision, and at the very least, will spend time understanding what my doctor thinks is happening and reconcile that with my own concerns/desires for treatment.

One option my doctor DID mention in our conversation last Friday is that even if I switch to Reyataz/Norvir/Truvada now, he still thinks I would be a great candidate for the Quad pill when it is released next year, which may be even easier to take than Atripla given its lack of CNS effects.

I will post again once I speak to my doctor. Thank you thank you thank you again! 
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: Inchlingblue on December 14, 2010, 10:51:31 am
I read Gallant's reply. It sounds like a good idea to do the bDNA test, assuming it doesn't take too long to get results.

Regardless of whether this is truly a blip or not, it might not be a bad idea to switch. There's also Isentress/Truvada. It's twice a day but it's an excellent combo with minimal if any side effects for most people.
Title: Re: Atripla Regimen Failure...or Temporary Blip?
Post by: eric48 on December 17, 2010, 12:08:33 am
No problemo...

So ... Thor has a bad cold, a bout of bad flue, a flue vaccine and a switch and ...

read this one below:


http://forums.poz.com/index.php?topic=35581.msg443233#msg443233

and pay a special attention to:

-------

They switched my regimen to Isentress and truvada and despite the fact I have no resistance issues the meds are no longer working . I'm wracking up a huge viral load now as well as huge copays

-------

Sure, that would be a hard price for a mere cold... Not that such as bad experience as listed above is for everyone.

But, apparently, a switch still comes with a risk...

Cheers!

Eric