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Author Topic: NRTI sparing regimens  (Read 5642 times)

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Offline JamieD

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NRTI sparing regimens
« on: July 31, 2007, 11:00:30 PM »
Is there anyone here on an NRTI sparing regimen? What are you taking if you are?

I am thinking of asking my doctor to switch me to an NRTI sparing regimen in order to avoid lipoatrophy/lipodystrophy. I can't/won't take Sustiva though, so it would have to be either Nevirapine or Rescriptor or maybe one of the new NNRTIs once its licensed. I can NOT keep taking my current regimen with my fears of lipo.

Offline Cerrid

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Re: NRTI sparing regimens
« Reply #1 on: August 01, 2007, 11:31:40 AM »
What is your current regimen? Do you have any resistance issues?

The recommended first-line therapies are 2 NRTI + 1 PI  or 2 NRTI + 1 NNRTI (+booster). If you choose Truvada or Kivexa/Epzicom as NRTI backbones, both have 2 NRTI included in one pill/day and both are considered very lipo-friendly nukes, unlike older combinations which include d4T or AZT (latter of which is partially metabolized to d4T).

Most PI raise lipid levels, too. However, this doesn't necessarily lead to lipodystrophy symptoms, there are a lot of factors involved in this process, not all of which are completely understood yet. There are also investigations about PI monotherapies going on but it's too early to tell anything conclusive about their longterm efficacy. About PI-only combos I don't know. They are probably rare.

As for NNRTI-only combos, there's a serious risk of resistance formation if you're not strictly adherent. Maybe a bit too risky for starters?

Then there's the possibility to combine PI and NNRTI. But as I said earlier, an increase of blood lipids is possible. The newer meds are usually restricted to second or third line therapies.

Just my 2 cents. You may want to talk to your doc to find you the best combination available to meet your desires.

"Boredom is always counterrevolutionary. Always." (Guy Debord)

Offline JamieD

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Re: NRTI sparing regimens
« Reply #2 on: August 01, 2007, 12:24:58 PM »
NRTI sparing regimen would be a PI + an NNRTI.

Offline JamieD

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Re: NRTI sparing regimens
« Reply #3 on: August 18, 2007, 10:06:40 PM »
bump

Offline Smoothstone

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Re: NRTI sparing regimens
« Reply #4 on: August 19, 2007, 04:18:36 AM »
I have taken Rescriptor, Viracept, Ziagen since 1997...luckily still not resistant...t cells went from 26 to 840....gradually over the 10 years...with some ups and down when I did treatment interruptions...I chose Rescriptor because an activist friend had done it for a couple months with seemingly no problems...stayed off of Sustiva because of the problems other friends experienced...Tried Viracept after stopping Crixivan, Ritonavir, Saquinavir because of side effect problems...beginning lipo,bad nausea,...the only challenge with Viracept was occasional "surprise diarrhea" thought I was going to pass gas, and would pass small amount of liquid... not painful, it was mostly at the beginning and would be about once a week, then once a month ,  ...haven't had that problem in years.....no lipo from this combo for me...individual differences of course may not apply to everyone...

I shared this even though it has an NRTI, Ziagen, because I think Ziagen is an exceptional NRTI...in my experience anyway.

Ziagen is a nuke but its been side effect free for me. I cant handle AZT at all...even 100 mg day wrecks me.I stopped the other NRTI because of side effect issues or didn't have as good brain penetration as Ziagen.    Ziagen has good brain penetration.  There is a test to screen for the small subset of folks who get an allergic reaction to Ziagen...

I just have to remember to take my combo. very lucky. I remember the times when I had really intolerable side effects. Its common to switch until you get the combo that works for you.  There is a way to stop and switch so you dont develop resistance. Consult your doc on that. Good luck.  Hank 


Offline aztecan

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Re: NRTI sparing regimens
« Reply #5 on: August 20, 2007, 12:02:26 PM »
Hey Jamie,

What is your present combo? I would have a talk with your doc about this and about the possibilities of developing some degree of lipo.

For the record, all of the meds could cause Lipo: the nukes, the non-nukes and the PIs. I've not heard of the fusion inhibitors doing it - at least not yet.

There also is some belief the HIV itself can lead to some degree of lipoatrophy, although nobody is sure about this.

There are a couple of new classes of drugs being introduced shortly, so you may want to wait for those. But, even they will have to be combined with other, already in use drugs.

Why are you worried about lipo at this time? Have you seen any signs of it beginning?

Just wondering why you are so worried about something that hasn't happened as yet.

HUGS,

Mark

"May your life preach more loudly than your lips."
~ William Ellery Channing (Unitarian Minister)

Offline newt

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Re: NRTI sparing regimens
« Reply #6 on: August 20, 2007, 12:39:16 PM »
No combination avoids the risk of lipodystrophy completely.

For the nukes, not using AZT, d4T or ddI eliminates nearly all the risk of drug-related fat loss

NNRTIs and PIs may both lead to fat accumulation, and changes to blood fats. The key word here is MAY.

Tenofovir or abacavir + 3TC or FTC + nevirapine prob has the lowest risk of fat abnormalities.

If this is related to concerns about body image and shape then choosing a non-nuke/PI combination ain't gonna ally these fears.  If anything, it increases the risk of some kind of fat abnormalities because of the possible combined effect on triglycerides/cholesterol of a PI + NNRTI mix and the difficulties these present around drug levels and side effects.

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

Offline JamieD

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Re: NRTI sparing regimens
« Reply #7 on: August 20, 2007, 05:40:17 PM »
Just wondering why you are so worried about something that hasn't happened as yet.


That's exactly the way I want it to stay, hence why I am concerned about it. That's most people's problem in general, they don't take care of things until there is already a problem. I like to take care of things before they happen.

My doctor agreed to switch me to Viramune. I will be taking Viramune and Reyataz. The NRTI-sparing regimens also help to avoid some of the mitochondrial toxicity associted with NRTI's.

Offline newt

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Re: NRTI sparing regimens
« Reply #8 on: August 21, 2007, 02:19:37 AM »
With what 3rd drug? And with/without a Norvir booster?
"The object is to be a well patient, not a good patient"

Offline JamieD

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Re: NRTI sparing regimens
« Reply #9 on: August 21, 2007, 05:58:50 PM »
There is no third drug, this is an NRTI sparing regimen. Boosted Reyataz.

Offline newt

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Re: NRTI sparing regimens
« Reply #10 on: August 21, 2007, 06:26:15 PM »
Good luck.  This is an untested one-drug-short of a full combo and I sincerly hope it works for you.

I sense there is no point posting further studies etc, like the ones that show tenofovir and abacavir are not associated with mitochondrial DNA depeletion, or the studies that suggest Viramune + Reyataz needs to be approached with caution until the possible interactions that may affect Reyataz levels adversly have been clarified, since your mind is made up.

As ever with ARVs, the proof of the pudding is in the eating. Viramune and Reyataz are strong drugs, and especially if your viral load is low/undetectable when you start the combo the chances of maintaing a viral load of <50 are fair.

Adding 1 nuke of course, 1 of the benign ones as far as fat loss goes, would make this a full formula combo and increase the likelihood of long-term success.

- matt
« Last Edit: August 21, 2007, 08:05:24 PM by newt »
"The object is to be a well patient, not a good patient"

Offline JamieD

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Re: NRTI sparing regimens
« Reply #11 on: August 22, 2007, 01:28:28 AM »
Newt-

I appreciate your input, I really do. From all of the NRTI sparing regimen studies that I have looked at they usually have two drugs, but sometimes 2 PI's and 1 non-nuke. I picked the combination of Reyataz and Nevirapine because that combination has been specifically tested in clinical trials. And my viral load is undetectable.  ;D I just got the results today.

My doctor is very willing to work with me on what I am and am not willing to take. He always tries to tell me about his experience with other patients when it comes to a certain combination, but seems pretty willing to let me do whatever it is I want. I guess my doctors both know that if they don't give me what I want that I will find some way of getting it anyway, so they would rather I do it under their care then on my own.

I recently talked to my ID about possibly getting off of HAART if my viral load is undetectable for a year, and using a TNF-alpha blocker. He said he wasn't too sure about that, but we have a year to discuss it.

Offline newt

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Re: NRTI sparing regimens
« Reply #12 on: August 22, 2007, 06:23:13 AM »
On the Viramune (nevirapine, NVP) and Reyataz (atazanavir, ATV) together point:

This trial:

Study to Evaluate the Influence of Nevirapine to Atazanavir in Steady State Equilibrium in HIV Patients will report in the next 6 months. It is looking at the question of ATV levels with NVP, and may provide useful data for you.

Successful use of boosted ATV + NVP was reported here:

NEVATA study for 28 patients at 24 weeks. The results in NEVATA are, as with many small, closely monitored studies, exceptionally good all round, both the ATV/NVP arm and the Kaletra + 2 nukes arm and therefore should be treated with some caution compared to "real world" use (or both sets of drugs).

But see also:

Ritonavir boosting may not overcome interaction between atazanavir and nevirapine (original abstract also here)

And:

Influence of tenofovir, nevirapine and efavirenz on ritonavir-boosted atazanavir pharmacokinetics in HIV-infected patients. found that NVP reduces ATV levels, even with boosting, to a very low amount at the end of the dose.

There are more of these reports showing reduce ATV levels with NVP.

For this nuke sparing combo it seems important to (1) take NVP 2 x day. NVP 1 x day can result in too low NVP levels and lead easily to resistance.  You need to protect the NVP by taking it 2 x day (2) get your ATV levels checked if possible, not standard in the US, but the test can be ordered, this will tell you if the ATV is present at an effective level  (therefore hunky dory combo).

On an anecdotal note, I know one person on this combo + 3TC (can't take tenofovir or abacavir, won't take d4T or AZT).  He had low ATV levels, but moved to taking the ATV at a different time to the NVP and they sorted themselves out.

Short version: boosted ATV + NVP may work as a maintenance therapy but is not well evaluated for effectiveness or durability. Adherence and maybe dosing schedule is critical to success. Risk: low ATV levels because of a NVP interaction = may lose ATV as a drug because of resistance, risk of NVP resistance from 1 x day dosing = may lose NNRTI class as a whole.  Benefits: no nukes = no nuke side effects, preserve nuke class for future use if necessary, potentially very good lipid wise.

On the mitochondrial toxicity point, this study shows no difference to mitochondrial DNA with tenofovir or abacavir:

Nucleoside analogue-related mitochondrial toxicity and link to lipoatrophy: effect of non-thymidine analogues abacavir and tenofovir. The key finding here is that people starting treatment with non-thymidine nucleosides (ie tenofovir or abacavir + 3TC), showed similar levels of mitochondria in adipocytes to ARV-naÔve and HIV-negative patients (report has a comparative table). This is a small genetic expression study. But many, many other studies show switching off the thymidine analogues (AZT, d4T) results in reversal fat loss for many people, which reinforces its findings.

Short version: drug related mitochondrial toxicity and therefore fat loss is not related to the non-thymidine analogues abacavir and tenofovir.

Since body shape changes are a concern for you I am gonna mention that the Royal Free, London has reported rapid subcutaneous fat gain in 1 in 19 people starting ATV (incidence prob. less than this overall, since it's kinda new to England and not many people take this drug), and this is something you should be aware of. << hopefully this will be presented at the BHIVA conference in Oct or next Apr.

Summary: boosted ATV + NVP may be a viable maintenance combo, provided you can organise the adherence well.  There are some cautions about drug levels and the possible consequences (eg resistance) and this may affect the durability/effectiveness of the combo. Abacavir and tenofovir do not seem to be connected to drug-related mitochondrial toxicity and therefore fat loss.

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

Offline JamieD

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Re: NRTI sparing regimens
« Reply #13 on: August 22, 2007, 06:48:03 AM »
Thank you. :)

The problem is that I have been taking Truvada, which also has the emitrabine (sp?). I really just want to go with the NRTI sparing combination now. I asked my doctor about getting me on expanded access for the Integrase Inhibitor. He said I am not resistant to any medications, so he would have to figure out how to spin it without lying.

P.S. I have been taking Truvada and unboosted Reyataz for 2 months now, and have no problems. My doctor did check my Reyataz levels and they were within normal ranges, about 4 weeks into therapy. I just take them at two seperate times during the day.

Offline JamieD

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Re: NRTI sparing regimens
« Reply #14 on: August 22, 2007, 06:52:38 AM »
Newt-

Do you think Rescriptor might be a better option to go along with Reyataz? I haven't made the change yet, not for another 5 days.

Offline newt

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Re: NRTI sparing regimens
« Reply #15 on: August 22, 2007, 07:04:25 AM »
The same interaction problems apply to Rescriptor.
"The object is to be a well patient, not a good patient"

Offline JamieD

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Re: NRTI sparing regimens
« Reply #16 on: August 22, 2007, 07:04:39 AM »
I hope I type this before you type another reply.

Newt-

My doctor shyed away from tenofovir because my neurologist put me on Lithium Citrate (it's a yummy syrup actually). They both can cause kidney problems.

Offline JamieD

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Re: NRTI sparing regimens
« Reply #17 on: August 22, 2007, 07:05:47 AM »
The same interaction problems apply to Rescriptor.

Really? AIDSMEDS says that it can increase the levels of all available Protease Inhibitors and that the dosage might need to be decreased.  ???

Offline newt

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Re: NRTI sparing regimens
« Reply #18 on: August 22, 2007, 07:59:45 AM »
Merck says delavirdine (Rescriptor) serum levels/effects may be increased by atazanavir and conversely, serum levels/effects of atazanavir may be increased by delavirdine.

http://www.merck.com/mmpe/lexicomp/atazanavir.html

The interaction is different, and will avoid the Reyataz low drug level thingy, but instead you get two high drug level issues to deal with, perhaps.  This combo is by and large unstudied, so you'd have to deal with these, if they happen, as they come. Increased drug levels will most likely = increased side effects.

Rescriptor has to be taken 3 x day though >:(

==

Since you are undetectable, I think ATV + NVP is workable, just needs some caution, and a plan B in case the combo don't work well enough.

NVP + ATZ not working will most likely see your doc suggesting a boosted PI + 2 nukes, or the complex 2 boosted PIs scenario, and goodbye non-nukes.  But if it does work, result  :)

This is maintenance therapy, so the parameters are different to starting combo (we need more maintenance studies).

===

Nuke-sparing/fat loss avoiding/lipid friendly/non-efavirenz combos would, to my mind be, with nukes:

NVP + Epzicom << possibly the most side effect free combo if you don't get the bad reactions to NVP/abacavir

Boosted Reyataz + Truvada or Epzicom (perhaps Invirase as an alternative)

Unboosted Reyataz + Epzicom

With 1 nuke:

NVP + boosted Reyataz + 3TC or abacavir

Without nukes:

A boosted PI monotherapy eg Kaletra, boosted Reyataz <<< promising these, if somewhat experimental

A boosted PI + 3TC or abacavir

I personally, for maintenance now my viral load is consistently under 50, would rather do (and am thinking about) NVP + Epzicom or a boosted PI (perhaps + 1 nuke).  But in all fairness, the last two PI based non-nuke options are prob no worse or better than your choice, except in terms of the consequences of treatment failure being better resistance wise.

With all cut-down combos, adherence is key, and I have to admit to myself that my adherence is, taking-drugs-on-time wise, not quite good enough for me to take the risk for the last two options i have listed.

- matt

Now playing: some James Taylor song
"The object is to be a well patient, not a good patient"

Offline newt

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Good luck JamieD
« Reply #19 on: August 23, 2007, 07:37:14 AM »
While you ain't (can't be) here I am here thinking about you.  And just wanted to wish you good luck.

Your doc is right about tenofovir and lithium, good reason to keep of the tenofovir.

Viramune (I am sure you know this) needs to be started at a 1 x a 200mg tab for the first two weeks to reduce the chance of side effects. Watch your liver test results for the first 3 months. Blood samples should ideally be taken every two weeks in the first two months to check liver function, then at the end of the third month.

And watch your lithium levels too cos there is some suggestion (a handful of case reports) that PIs like Reyataz may reduce the level of lithium in the body (this is easy to monitor and adjust).

And see if you can get your doc to order a therapeutic drug monitoring test to check the Reyataz levels are okay, after a month or so.

So maybe for a few weeks it'll feel like being a bit of a prof. patient, but in the long term, shortly, if your viral load stays undetectable and the drug levels/interactions are sorted and the Viramune agrees with you, then plain sailing, n you can get back to real life eh?

Sincerely, best of luck mr

- matt
« Last Edit: August 23, 2007, 08:59:29 AM by newt »
"The object is to be a well patient, not a good patient"

Offline JamieD

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Re: NRTI sparing regimens
« Reply #20 on: August 30, 2007, 08:41:33 PM »
Thanks, Matt.

Ug. Who are you telling? I have become a fat cow on Reyataz.  :-\ I went from being 145 pounds to 154 pounds. I am 5'11.  :'( I need to start purging again.

Offline Miss Philicia

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Re: NRTI sparing regimens
« Reply #21 on: March 10, 2008, 01:36:56 AM »
bump
"Iíve slept with enough men to know that Iím not gay"

Offline thunter34

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Re: NRTI sparing regimens
« Reply #22 on: March 10, 2008, 01:40:07 AM »
AIDS isn't for sissies.

Offline Miss Philicia

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Re: NRTI sparing regimens
« Reply #23 on: March 10, 2008, 01:42:21 AM »
subtle.

What's a girl to do?  I'm thinking of dumping Isentress for Viramune so that I can get rid of my lipo.
"Iíve slept with enough men to know that Iím not gay"

Offline thunter34

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Re: NRTI sparing regimens
« Reply #24 on: March 10, 2008, 01:43:46 AM »
What's a girl to do?  I'm thinking of dumping Isentress for Viramune so that I can get rid of my lipo.

I hear Lithium and coconut oil work wonders for keeping a girlish figure.
AIDS isn't for sissies.

Offline Miss Philicia

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Re: NRTI sparing regimens
« Reply #25 on: March 10, 2008, 01:45:49 AM »
I hear Lithium and coconut oil work wonders for keeping a girlish figure.

I have some prochlorperazine and fish oil supplements -- will that work?
"Iíve slept with enough men to know that Iím not gay"

Offline thunter34

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Re: NRTI sparing regimens
« Reply #26 on: March 10, 2008, 01:48:41 AM »
I have some prochlorperazine and fish oil supplements -- will that work?

girl, as long as you're properly purging any route will work.
AIDS isn't for sissies.

Offline Miss Philicia

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Re: NRTI sparing regimens
« Reply #27 on: March 10, 2008, 01:51:04 AM »
girl, as long as you're properly purging any route will work.

I like being thin, what can I say?  Helps when I go for that Project Rungay try out.

I sometimes go 20+ hours without eating. I only eat because I have to stay alive, but I eat nothing more then what I need. Like in the past 24 hours I have had 2 slices of bread, 1 slice of a very expensive organic cheddar cheese, and a glass of gingerale. It took so much out of me to force myself to eat the bread and cheese.
« Last Edit: March 10, 2008, 01:53:54 AM by philly267 »
"Iíve slept with enough men to know that Iím not gay"

 


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