Stubbornly detectable VL - next treatment options?

[thor]

Hi all, you all were so helpful to me in December when I last wrote about issues I was having with Atripla. I hope you might be able to help me think through my next ARV treatment move.

I was diagnosed in 8/09 with VL 8000 and CD4 360 (22%), and no drug resistance on my genotype test. I began taking Atripla in 12/09, and recorded the following results:
3/10 - VL 2800, 4/10 - VL UD, CD4 470 (27%); 7/10 - VL 95; 10/10 - VL 1060, CD4 560 (36%); 12/10 - VL 393; 1/11 - VL 87, 4/11 - VL 660, CD4 510 (31%).

Due to the persistently detectable VL, I made the switch in 4/11 to Reyataz/Truvada/Norvir. I then got labs done on 7/15: VL 301, CD4 489 (35%). VL still stubbornly detectable.

I've also tried to get resistance genotype tests done in 4/10, 10/10, and 4/11, but they always come back inconclusive (insufficient virus to run the test).

My doctor is now concerned that R/T/N alone is not working, and he suggests that we, 1.) Do another VL reading at end-August, 2.) if VL is still detectable, we either add an additional ARV to R/T/N, or go on a 1-month "treatment interruption" in order to run a genotype test. He suspects that I may have FTC resistance that didn't show up on my pre-treatment genotype test in 8/09, and would like to have confirmation before moving forward.

So, my question is, if my VL does stay stubbornly detectable, which of these options seems most reasonable? If I add another ARV, which would it be? I've also had another doctor suggest to me a switch to Selzentry + Isentress + Truvada (contingent upon a favorable Trofile test). That doctor believes the S/I/T combo could be less taxing in terms of long-term side effects, particularly as it relates to PI-associated lipohypertrophy, and that S/I/T has significant T-cell regenerating potential. My current doctor tells me he would be willing to prescribe S/I/T, but that he's concerned about the lower "barrier to resistance" for S/I compared to the Norvir-boosted PI in my current regimen, particularly for a patient with suspected but unconfirmed drug resistance, and a virus that is proving difficult to suppress. 

I should add that I'm extremely compliant with my medication (likely >99% adherence, if not 100%), and that a 2x day dosing regimen doesn't worry me. I believe I'm in extremely good health - early 30s, strong organ function and healthy lipid profile, marathon runner, non-smoker and no drugs/alcohol. Regularly screened negative for HCV, syphillis, gonorrhea. And of course, I hope to stay this way for a long time!

Thank you all kindly for your help. I really appreciate the wisdom and support you provide in this forum.   

[Inchlingblue]

Have you had the branch DNA test done for measuring viral load?

If you search on here for it you can see previous threads where it's been discussed.

[eric48]

Hi Thor,

Welcome to the forum !

I sympathize that this must be very frustrating ...

Depending on where you live treatment management guidelines may differ. Where I live the rules are the most restrictive I have heard of so far.

Unless the following checkpoints are passed, virological failure is declared and patient'case transferred to virologist experts; I looked into it because I myself was close to those limits.

CHECKPOINTS
***********
Here, targets are
- decrease of 1 log after one month
- decrease of 2 log and/or < 400 after 3 months
- <50 after 6 months

You did not pass checkpoint number 2 to get started with...

Genotyping can be done on earlier blood samples as labs are supposed to store blood samples for a year.

depending on the genotype laboratory minimal VL acceptable for proper genotype is 1000, 800 or even 500. My doc said that they sometimes do it as low as 200 but will not rely too much on the data in that case.

because I happen to come out with a clean bill, I can only recall a bit of the research I did at that time.

On top of memory (and please do not sue me if I make a mistake...), genotype is not the only way to go.
Phenotype is an alternative option.

you may learn more here:

http://hivdb.stanford.edu/index.html

http://hivdb.stanford.edu/pages/documentPage/genoPheno.html

http://www.medscape.com/viewarticle/448717_3

So there are 3 methods:
-genotype (takes 3 weeks of intense lab technician work)
-phenotype (time consuming/very costly)
- and an alternative which name I do not remember but some king of computer assisted combination of both (in order to reduce cost of a complete phenotype screening)

I am not in your shoes, but, for me that was a close call. Should the issue be as puzzling as what you describe I would certainly write a detailled letter to the 2-3 top virologists in the country and require their immediate attention.

Because there are many options (and you are not at death door), the trial and error is one treatment strategy.

The issue is way too serious to be left to a guessing game.

That being said, if tropism test is favorable the proposed S/I/T seems a fair enough deal.

But what if the tropism test comes back unfavorable ?

It is a tough one, but feeling healthy will help you go through this...

Cheers

Eric

[newt]

In these circumstances I wouldn't have chosen atazanavir as the PI, I would try darunavir (Prezista), or darunavir + some other major drug like raltegravir (Isentress) + 1 or more nukes.

Alternatively, try a new lab for a viral load test, and/or look at a test called TDM (therapeutic drug monitoring) to see if you are getting the drug into you body properly.

FTC resistance alone should make little difference if you are on tenofovir (which you are).  FTC-resistant HIV is typically extra susceptible to tenofovir. Plus suspecting resistance is kinda speculative. The difference between FTC working and not working here is probably not equal to the extra 1 log drop in viral load you are after.

Wider nuke resistance, yes, you need a few weeks off treatment to investigate this.

Also, I will say, some of the the latest viral load tests are kinda flaky and what equates to the older "undetectable" is not obvious. If it's the new Taqman test 250 copies/ml is probably adequate but 400 might be acceptable depending on the lab, if it's the Realtime test then 40 or 50 is still the target.

- matt

[eric48]

Hi Thor,

It is not clear if you have access to first in class testing/counselling/meds or live in an area where your doctor has to compose with what is available. Accessible ressources, to you and your health care provider are not clear.

With all due respect, treatment strategies are not the same whether you live nearby the NIH or a major Research facility or in a small village in the bush.

In the  trial and error guess work, Duranavir might have had a better rating.

Its potency it described in figure 6 of the article below:
http://www.iasusa.org/pub/topics/2010/issue3/104.pdf

(please bear in mind that :
A- as long as drug is potent enough, it is potent enough, there is no need to go for super super potent
B- in presence of identified resistance , the concept is pointless (the potency index is valid only in the absence of resistance to that given drug)

In this context, as it appeared in the initial stages of your history, the strategy followed by your doctor makes sense, eventhough, as stated above there are some strategies that might have been better.

Some doctors like to start with a 'soft' strategy then move to more daring one if needed
Some doctor will choose the heaviest hammer to get started with
Some doctor prescribe 'blind' without even access to a VL reading (think of some villages in Africa)
Some doctors will do tons of test before making any decision
Some doctor are limited in their approach by economical factors...(insurance...)

Your VL is playing hide and seek and makes it unusually difficult for your doctor.

Therefore seeking additional information on your virus (by alternative methods or alternative lab) as well as seeking additional information on in-vivo efficacy with TDM should be actively considered (once again, if this is available to you)

The good news though is that you seem to have access to the most modern meds (like celzentry)

Some people have to endure this noisy response in VL for a while before the solution is found, and at CD4 like yours there is little risk.

However distressing it may be, please keep faith !

My doctor commented that in modern day clinical care, the very few cases that can not be helped out are those late presenters (CD4 <50) with additional health problems (TB, etc...)

Cheers!

Eric

[james3000]

I had a similar problem I had to have TDM and found levels of 2 drugs were low.

I am On 3tc Isentress Intellence Prezista and norvir .  my body metabolize the drugs at a faster rate so had to increase dose I will not know until the end of September if it is working.

[thor]

Thank you all for the help!

I'm getting the Trofile test (to determine Selzentry eligibility) and another VL done on Monday. I'll also ask my doctor about a few of the ideas several of you mentioned, such as switching the type of VL test and measuring drug absorption.

I'm going to get to undetectable one way or another! Thanks again for all the support and kind words.