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Author Topic: Tim & Matt.. should I switch, and what to?  (Read 2510 times)

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Offline Peter Staley

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Tim & Matt.. should I switch, and what to?
« on: December 09, 2008, 01:20:01 PM »
Dear Tim Horn and Matt (aka Newt) and any others that care to chime in:

Looking for some 2nd & 3rd opinions before my doctor's appointment on Thursday morning.  He's been suggesting to me that with all the new drugs on the market, it might be worth reviewing my current regimen to see if it could be improved or changed completely.

See my sig line from my previous history of meds.  I'm currently on a weird regimen of Reyataz/Norvir/Viramune/Truvada.  The reason for taking a 3 class regimen was security -- I have plenty of NRTI resistance, but potentially only low-level or intermediate resistance to the drugs in Truvada.  I asked to include the Viramune, just in case the Truvada didn't do its part.  In other words, I might be on an effective Viramune/Reyataz regimen.

However, the FDA announced a few months back that Viramune and Reyataz shouldn't be used together since each screws up the blood levels of the other.

Then again, I've largely been undetectable since starting this regimen, and side-effects free, with the following exceptions.  I was diagnosed with osteopenia a few years back, but I don't have a baseline to compare my bone density numbers to, and they have not gotten worse (around 2.2).  I've had occasional above-normal levels of creatinine.  I have to take the highest dose of Crestor in order to keep my cholesterol below 200.

I've got resistance tests from 2003, and will include the genotype results below.  The phenotype conflicted with genotype on one drug only -- it said I was just under the cut-off for abacavir (and OVER for all the other NRTIs).

I'm wondering if there's a nice NRTI-sparing regimen I could take instead, that's lipo friendly.  I don't care about once a day -- I'm 100% compliant on twice a day as it is.

Any suggestions?  Of course, a good argument can be made for not changing anything, regardless of the FDA's recent warning on my combo.  My numbers say it's working thus far.

Here's my genotype from 2003, as interpreted on Stanford's HIVdb...

No PI or NNRTI mutations (yeah!)

NRTI Resistance Mutations:   M41L, D67N, T69D, K70R, T215F, K219Q
NNRTI Resistance Mutations:   None
Other Mutations:   V179I

Nucleoside RTI
lamivudine (3TC)                    Potential low-level resistance
abacavir (ABC)                           Intermediate resistance
zidovudine (AZT)                    High-level resistance
stavudine (D4T)                           High-level resistance
didanosine (DDI)                           High-level resistance
emtricitabine (FTC)                   Potential low-level resistance
tenofovir (TDF)                           Intermediate resistance

RT Comments

    * M41L usually occurs with T215Y. Together these mutations confer intermediate-to-high level resistance to AZT and d4T and a lower level of resistance to ddI, ABC, and TDF.
    * D67N contributes some degree of resistance to each of the NRTIs except 3TC and FTC. It usually occurs with mutations at positions 70 or 215.
    * T69D contributes resistance to ddI and d4T.
    * K70R causes low-level AZT, d4T, and possibly TDF resistance and appears to have little if any effect on the other NRTIs.
    * V179I is a common polymorphism which occurs more commonly in NNRTI-treated isolates. However, it does not reduce NNRTI susceptibility.
    * T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and to a lesser extent TDF.
    * K219Q/E decrease AZT and probably d4T susceptibility when present with K70R or T215Y/F but have little if any effect on the remaining NRTIs.

Offline veritas

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Re: Tim & Matt.. should I switch, and what to?
« Reply #1 on: December 09, 2008, 01:57:23 PM »

Peter,

You seem to have quite a few options, especially with no pi or nnrti mutations. Of course every time you change your meds you run the risk of AE's. I wish I had that many options. I am presently on Isentress, DRV/RT,truvada and my vl <50 and cd4 1200. When I started Isentress my cd4's increased by 200. Off the top of my head you probably could use Isentress,DRV/rt,intelence. This combo would be 3 active drugs and no nrti. There might be better combo's but those three are obvious. Good luck.

veritas

Offline Tim Horn

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Re: Tim & Matt.. should I switch, and what to?
« Reply #2 on: December 09, 2008, 02:03:53 PM »
A couple of thoughts:

1) Swap the Reyataz/Norvir for Prezista/Norvir. While Norvir-boosted Prezista increases the AUC of Viramune by 27 percent and the Cmin by 47 percent, Viramune does not appear to have any effect on the AUC or Cmin of Prezista. Dosing of both drugs is therefore standard. As you're treatment experienced, this likely means twice-daily 600 mg Prezista plus 100 mg Norvir. This basically doubles your daily Norvir intake, which may not be something you'd want to do (there's a potential for worsening lipid outcomes). You may also want to consider the 800mg/100mg dosing option used for treatment-naives, given that you're getting additional coverage from the Viramune to make up for the low-to-intermediate resistance to Truvada -- but this certainly isn't the standard approach, especially whe we don't really know if your virus has accumulated any PI mutations since your last DR test in '03).

2) Swap the Viramune for Isentress. One of the fears with Isentress is its low resistance barrer -- only one key mutation is needed to confer high-level resistance to the drug. However, this is also the case with Viramune. Given that you're also on a Norvir-boosted PI and a moderately- to highly-effective NRTI backbone, Isentress should keep you covered. Of course, it's nice to be able to call upon Isentress if you ever need to switch your regimen to due virologic failure. It's one of the best options we have in this regard.

Isentress doesn't interact with NNRTIs and PIs via the P450 enzyme system, making it a relatively interaction-friendly med. However, Reyataz inhibits another enzyme system -- UGT1A1 -- which can result in increased blood levels of Isentress. Fortunately, we know enough about the use of these drugs in three clinical trials of Isentress -- Studies 005, 018 and 019 -- to know that they can be used safely together.

3) The use of Selzentry instead of Viraume would be an interesting switch. However, with an undetectable viral load, you're unlikely to get any vital information with necessary tropism testing.

4) As for switching to Sustiva -- I know this is something you're not keen on -- this is also considered problematic in treatment-experienced patients when Reyataz is in the combination. In fact, it's best not to use Sustiva and Viramune at all if you're treatment experienced.

5) Regarding your NRTI backbone, looks as if you're doing okay on Truvada and should simply stick with it. Yeah, you might do just as well switching to Epzicom -- here, too, you'd have low- to intermediate-level resistance -- but, let's face it -- Truvada seems to be up against fewer safety and efficacy concerns.

I have no doubt Matt will have more food for thought,

Tim


Offline Tim Horn

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Re: Tim & Matt.. should I switch, and what to?
« Reply #3 on: December 09, 2008, 02:27:36 PM »
Veritas's suggested nuc-free combo --Prezista/Norvir/Isentress/Intelence -- is intriguing. The only thing that makes me somewhat nervous about this is the fact that Intelence blood levels are reduced -- the AUC drops by more than 35 percent and the Cmin by almost 50 percent -- when used with Prezista. However, there's certainly clinical trial data indicating that Prezista and Intelence can be used effectively together. In fact, early data from a small trial in "deep salvage" patients taking the four drugs listed above proved astonishing. Thing is, we're not really talking about the need for a "deep salvage" regimen, but rather simple changes to circumvent a *potentially* troublesome drug interaction in your existing regimen.   



Offline newt

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Re: Tim & Matt.. should I switch, and what to?
« Reply #4 on: December 09, 2008, 03:55:07 PM »
Hello

Option 2 from Tim's list ie swap the Nevirapine for Isentress.

Apart from its probably nice metabolic profile (no lipid or liver involvement etc) Isentress seems, so far, to be light on side effects and heavy on good immunological effects (bonus). As we know, these tend to come to light later, and this being new drug, these is scope for discovery. Of note is rash, and perhaps depressive symptoms is a small number of people.

I would try and keep on the low-Norvir Reyataz if possible. Prezista is a goodie, but twice as much Norvir. Plus there's reasons to keep it in hand right now as it's a resistance buster, and very different in mutation profile to Reyataz.

The results from the DUET studies on Intelence and Prezista were very good. The Prezista 800/100 "naive" dosing seems pretty robust though, and it is a moot point whether having no pi mutations you count as "experienced" enough to subject your liver to 200mg Norvir. So, being very modern, Prezista 800 + Intelence may be an option.

- matt

I am adding a PS;

Just to add there is merit in the if it aint broke dont fix it approach. In the UK we would probably reach for some thereaputic drug monitoring to check the levels of Reyataz first perhaps, and liver enzymes for NVP adverse effects. Clinically, if this combo is working and not causing problems, then the rather fast move by BMS to amend the labelling could be ignored.




« Last Edit: December 09, 2008, 04:56:30 PM by newt »
"The object is to be a well patient, not a good patient"

Offline Peter Staley

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Re: Tim & Matt.. should I switch, and what to?
« Reply #5 on: December 10, 2008, 11:59:38 AM »
Thanks Veritas, Tim and Matt:

I also got a PM from another member that suggested this:

Quote
Re your meds

Another suggestion could be for a combo made up of Viramune, Celzentry and Isentress.  This combo would be NRTI sparing - so would control for resistance as well as the possible renal and osteopenic issues.

This combo would also be PI sparing - potentially having a beneficial effect on cholesterol and other CV health markers.

It's a twice daily combo but it could eliminate a number of the issues that you have described.  The only other consideration is that you would need the CCR5 tropism assay for Celzentry.

Hope this is usefull.

I realize the Selzentry is an issue, since I'd have to go off therapy in order to raise my VL enough to to the tropism assay (do folks do this, or is that a crazy idea?).

FYI -- I actually attempted to get TDM testing done, but probably messed up the peak testing (did it one hour after dosing, and now I'm told it should have been at least 2 hours).  However, the trough test on Reyataz showed it barely above the minimum end of the reference range.  I don't have them in front of me, but I think the Viramune levels were okay.  And for some reason, they weren't able to obtain tenofovir levels from the testing sample (the Brooklyn LabCorp branch didn't know what the fuck they were doing, and I'm convinced they didn't use the right tube which was sent to their NJ branch for shipping to Consolidated Laboratory Services in CA).

I guess the only reason I like the idea of an NRTI-sparing regimen (besides not having to worry if an NRTI is wasted on me because of resistance) is my probably unwarranted fear that tenofovir is testing my bones and kidneys.  I know, I know -- not very rational based on its overall toxicity profile, which is pretty damn good.

I'll probably end up changing nothing, but we'll see what the doc says (Michael Rendel -- a really smart one).

Peter

Offline Miss Philicia

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Re: Tim & Matt.. should I switch, and what to?
« Reply #6 on: December 10, 2008, 12:48:22 PM »
I'd have to go off therapy in order to raise my VL enough to to the tropism assay (do folks do this, or is that a crazy idea?).

No, it's not crazy.  My doctor's office does it, though I've personally not done it yet I'd not hesitate if needed.

Otherwise I'd probably take every opportunity to fit Isentress in to your prospective regimen somehow.
"Iíve slept with enough men to know that Iím not gay"

Offline newt

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Re: Tim & Matt.. should I switch, and what to?
« Reply #7 on: December 10, 2008, 02:30:38 PM »
Going off therapy with suppressed viral load for a test is nutty in my book. Pretty much every doctor I know in the UK does switch + if it don't work, then test (while staying on treatment) .. cos it's safer for the patient. i am sure there are some, many even, who don't though.

- matt
"The object is to be a well patient, not a good patient"

Offline Miss Philicia

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Re: Tim & Matt.. should I switch, and what to?
« Reply #8 on: December 10, 2008, 03:22:40 PM »
I should have been more careful with that post.  I shouldn't have implied that my doctor's office does this regularly, just that it was suggested in one instance and I forget what the exact conditions were.  My thinking was that if one is having other side effects that necessitated a med switch while having an undetectable viral load, it could be viewed as prudent to go off therapy for a brief time to allow your VL to climb over that small threshold for testing purposes, and done in as controlled manner as possible.  And, of course, I was thinking in the contest of a LTS with a history of resistance issues where the doctor would not want to make treatment decisions while pissing into the wind.

Sorry if I was misunderstood.
"Iíve slept with enough men to know that Iím not gay"

Offline Peter Staley

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Re: Tim & Matt.. should I switch, and what to?
« Reply #9 on: December 12, 2008, 07:15:33 AM »
Thanks everyone for the sage advice.  I met with my doctor yesterday morning, and we reviewed all the options suggested above.

We decided to stick with the current regimen.  Regardless of recent labeling changes, my numbers say the meds are working (or at least some of them are).  All the alternative regimens discussed are typically tried in salvage situations, and I'm not there yet (knock on wood).

Once we have more long-term side effects data on the seemingly wonderful newer meds (especially Isentress), then we'll both feel comfortable making a non-salvage switch.

Again, thanks for all the input.

Peter

Offline veritas

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Re: Tim & Matt.. should I switch, and what to?
« Reply #10 on: December 12, 2008, 07:24:46 AM »

Peter,

Sounds like a good move, as Matt said "If it ain't broke don't fix it!".

veritas

 


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