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Meds, Mind, Body & Benefits => Questions About Treatment & Side Effects => Topic started by: Assurbanipal on May 29, 2008, 08:11:45 pm

Title: Viramune and my doc
Post by: Assurbanipal on May 29, 2008, 08:11:45 pm
Getting ready for an appointment with the ID doc next week, and I talked to her on the phone about wanting to discuss a med switch because my cholesterol and triglycerides keep going up.  (We need to talk about testosterone too, but that's a different story). 

About three months ago, worried about effectiveness and cholesterol I posted a thread about possibly switching off Kaletra to Sustiva and Minismum suggested I look into Viramune instead (thanks Mum).  I looked into it and it seemed like it could really be helpful.  But my ID doc didn't like the idea and said we'd have to monitor for liver issues.  (Note, monitoring for liver problems seems to be standard of care, but the studies warning about likely significant liver issues appear to be targeted mainly at people whose CD4's were 10 times mine when they started HAART).

Months go by, more tests and and visit to the GP . . .he is suggesting Tricor for the triglycerides which comes with "careful monitoring for liver toxicity"  -- so I'm thinking as long as we are going to be monitoring for liver toxicity why not switch Kaletra for Viramune and monitor it instead of Tricor?

When I suggested Viramune to my ID doc 4 months ago she was not encouraging in person -- but pressing her then and over the phone this past week I didn't get anything that felt really solid, but instead heard:
"Well, I was hoping you could stay on Kaletra/Truvada for 10 years"  (But couldn't I go back or try a different option if Truvada/ Viramune doesn't work)
"You started with 40 CD4 and what if Viramune doesn't work?" (Well, can't we step up the testing for a couple of months while we are testing liver toxicity)
"Your creatinine level was elevated on one test "  (I went camping , got dehydrated and it screwed up the kidney tests a little)
"Viramune is an old drug; I would only use that if more recent drugs are not working" (But it is an alternate first line of treatment)

So . . . I'm reaching out to see if folks have any suggestions on why my doc might be so negative on Viramune.  Is it
a) I'm being too blithe about going off a regimen that's working (but which has my cholesterol and triglycerides going up 50-100 every quarter)
b) Something else I'm not hearing right up above
c) Some prior info about Viramune that maybe she can't quite put her finger on in conversation
d) Old theories about viramune that have changed?
e) . . .??? ??? ???

So any help, theories, etc. solicited.

(This "being an active partner with the doctor" sounded a lot easier in theory . . . :) )

Thanks
Assurbanipal
Title: Re: Viramune and my doc
Post by: Matty the Damned on May 29, 2008, 08:30:37 pm
Viramune is usually not given to men whose CD4 counts are above 400 prior to starting the viramune. In women that cut-off is 250. There's a potential for serious liver damage.

MtD
Title: Re: Viramune and my doc
Post by: newt on May 29, 2008, 09:13:51 pm
Yes tis true Viramune can be hard on the liver and in very few people causes a allergic reaction, but..old or not it works and if your liver is okay on it and you don;t get a rash it can be a goodie, relatively side effect free.

MtD makes a good point on CD4 count.

There are alternatives: Reyataz for one and the new NNRTI etravirine plus the integrase inhibitor Isentress. If your doc is worried about drugs being "old" there are plenty of new ones that are kinder to lipids than Kaletra.

- matt
Title: Re: Viramune and my doc
Post by: Assurbanipal on May 29, 2008, 09:42:46 pm
Viramune is usually not given to men whose CD4 counts are above 400 prior to starting the viramune. In women that cut-off is 250. There's a potential for serious liver damage.

MtD

Thanks Matty and Newt

The warning on starting with over 400 CD4 cells is somewhat ambiguously phrased.  For instance the lessons on this site appear to refer to CD4 count at the time of starting HAART  (when my cd4 was 40)
" As for men, liver problems are more likely to occur if the T-cell count is above 400 at the time of starting anti-HIV treatment for the first time. "
http://www.aidsmeds.com/archive/Viramune_1616.shtml


The DHHS guidelines refer to the warning in a paragraph about treatment naive patients
"Serious hepatic events have been observed when nevirapine was initiated in treatment-naïve patients. These events generally occur within the first few weeks of treatment. In addition to experiencing elevated serum transaminases, approximately half of the patients also develop skin rash, with or without fever or flu-like symptoms. Women with higher CD4 counts appear to be at highest risk [129, 130]. A 12-fold higher incidence of symptomatic hepatic events was seen in women (including pregnant women) with CD4 counts >250 cells/mm3 at the time of nevirapine initiation when compared with women with CD4 counts <250 cells/mm3 (11.0% vs. 0.9%). An increased risk was also seen in men with pretreatment CD4 counts >400 cells/mm 3 when compared with men with pretreatment CD4 counts <400 cells/mm3 (6.3% vs. 1.2%). Most of these patients had no identifiable underlying hepatic abnormalities. In some cases, hepatic injuries continued to progress despite discontinuation of nevirapine [129, 131]."
http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf


I've been trying to find copies of the cited papers, but without luck so far.

Do you know of an additional source that could clear this up?

**Edited to add

Further reading brought up the 2006 Recommendations of the International Aids Society - USA Panel.  They appear to have addressed head on the uncertainty about whether the 400 CD4 count threshold should be applied based on CD4 count at the start of HAART or at the start of Viramune treatment.  . . .and they said "we don't know"
"Nevirapine has virologic activity similar to efavirenz and is safe for the fetus in all stages of pregnancy if appropriate for the mother. There is a risk of potentially fatal hepatotoxicity in women with CD4 cell counts higher than 250/μL and in men with counts higher than 400/μL. Data from Thailand, 24 where the drug was well tolerated in the patients studied, have raised the question about the true risk to women and whether it applies to all populations. It is not known whether switching from efavirenz to nevirapine when the CD4 cell count has risen above these thresholds while receiving treatment is associated with the same risk as starting nevirapine de novo in a treatment-naive woman or man with CD4 cell counts higher than 250 or 400 cells/μL, respectively."  [emphasis added]
http://www.apla.org/programs/treatment/IAS_adult_treatment_guidelines.pdf

So it's a potential unknown risk, but one that would appear to be manageable with careful monitoring during the first few weeks.

Newt, thanks for the additional helpful suggestions, guess I should spend more time looking at Reyataz and etravirine too (but I always secretly wanted to have blue  skin  :) )


Thanks
A

Title: Re: Viramune and my doc
Post by: Matty the Damned on May 29, 2008, 11:23:11 pm
Hey A,

The section of the Lessons that I read say this about Viramune and hepatotoxicity:

† Liver problems have occurred in several patients taking Viramune who start the drug when their CD4 (T4 cell) counts are above certain levels. Women with over 250 CD4 cells and men with over 400 CD4 cells prior to starting Viramune should not take Viramune.

(link) (http://www.aidsmeds.com/articles/WhenToStart_4759.shtml)

MtD
Title: Re: Viramune and my doc
Post by: penguin on May 30, 2008, 04:46:28 am
you might be intereted in this study from march 08 - http://www.journals.uchicago.edu/doi/abs/10.1086/528861 (http://www.journals.uchicago.edu/doi/abs/10.1086/528861)

aidsmeds normal english  summary of it is here - http://www.aidsmeds.com/articles/aids_viramune_nevirapine_1667_14112.shtml (http://www.aidsmeds.com/articles/aids_viramune_nevirapine_1667_14112.shtml)

happy switching, whateve you decide... kate

Title: Re: Viramune and my doc
Post by: trellium on May 30, 2008, 05:44:29 am
Here's another write-up of the ATHENA Cohort Study

Switching to Nevirapine (Viramune) Appears Generally Safe for Patients with High CD4 Cell Counts
http://www.hivandhepatitis.com/2007icr/icaac/docs/092807_c.html
Title: Re: Viramune and my doc
Post by: Assurbanipal on May 30, 2008, 07:17:01 am
Thanks for the additional info folks, you have all been so helpful

MtD
Thanks for the posting and the link.  I appreciate your help in posting the links -- it can be really hard to chase down all this information.  In this case, though, the link is to the footnote at the bottom of a table that is labeled "Preferred" or "Alternative" Regimens for HIV-Positive People Beginning HIV Treatment for the First Time

The AIDSMEDS text says the table is based on the DHHS materials, but looking at the footnote to the comparable table in the DHHS guidelines it is phrased a little differently than the AIDSMEDS table footnote. 

The DHHS guideline footnote says "Nevirapine should not be initiated the following treatment-naïve patients: women with CD4 count >250 cells/mm3 or in men with CD4 count >400 cells/mm3 because of increased risk for symptomatic hepatic events in these patients" [emphasis added]


Kate

Thanks for the Athena study summaries, which suggest that the CD4 thresholds can be applied based on CD4 counts when beginning HAART, if VL at the time of switch is undetectable..

Trellium
Thanks for the additional ATHENA reference and the metastudy as well -- I saw in your back posts that your doctor had a similar reaction to the idea of Viramune (mine also appeared to be willing to swap Sustiva for Kaletra, instead).  Solidarity and all that  :)



Assurbanipal
Title: Re: Viramune and my doc
Post by: Peter Staley on May 30, 2008, 11:27:41 am
Assurbanipal -- please consider the Reyataz + Norvir option instead, as Matt pointed out.  It's one of the few protease inhibitors that doesn't mess up your lipid levels, and you won't have the liver worries that Viramune can bring.

Peter Staley
Founder
AIDSmeds.com

P.S.  the CD4 warnings on Viramune are only if you haven't been on therapy before.
Title: Re: Viramune and my doc
Post by: Assurbanipal on May 30, 2008, 07:00:32 pm
Thanks Peter

I am going back to look at Reyataz and Intelence. 

Doing that it strikes me I've been sorting through the drugs using a few strategies, and that setting them out here in this post might get some helpful feedback from  people on whether they think they make any sense or are missing some big issues. So here goes:

Strategies
1) Side effects aren't guaranteed and are infrequent. The chance of getting a side effect on one drug isn't well correlated with the chance it occurs on another drug. Thus if one has side effects on an existing regimen there may be some benefit to rolling the dice on a new regimen,
2) If a common side effect did occur would if be manageable?  Which side effects play to my pre-HAART weaknesses or strengths?
3) Kaletra isn't great -- but it is currently keeping the viral load down and side effects are of the slowly building bad news type rather than the immediately intolerable variety, so how to maximize the opportunity to return to Kaletra if the new drugs don't work?
4) Other than one false alarm on the kidneys, it doesn't appear that Truvada is giving me any significant grief (what's a few more burps after all? :)) so why roll the dice on another medicine there?


Applying them to different options -- boosted Reyataz, Intelence, Viramune:
1) applies to all three
2) a) boosted Reyataz potential side effects include increased glucose levels.  Pre-HAART I was high normal for cholesterol and glucose -- I've been able to manage glucose levels down with increased exercise and dietary changes, but it's a weak spot and I don't know if Kaletra was increasing glucose levels as well or if Reyataz would be worse. Turning yellow (manageable)
b) Intelence -- rash (should manifest quickly) and nausea (always had a very strong stomach) so not a problem
c) Viramune -- potential skin and liver problems require careful monitoring at start of treatment (right now I can do that, if I move back to full time employment that will become more difficult)
3) If boosted Reyataz fails there's a good chance to lose Kaletra; not an issue for the other two
4) Used as a screen

So based on the above applied to the list of drugs, I've been looking mainly at swapping Kaletra for viramune, intelence or (distant third) sustiva (as suggested by the doctor on the phone). Any decision will be made with the doctor, and maybe with some more tests too, but the feedback from people here who have been thinking through and living through these issues for so much longer has been invaluable.  Thank you for putting this framework and forum together.

Assurbanipal
Title: Re: Viramune and my doc
Post by: newt on May 30, 2008, 07:54:18 pm
My dear friend...

..the proof of the pudding is in the eating with ARVs. you can read all the papers you and I like, but until the complete metabolic/genetic picture for each drug is transparent (which it will never be) the proof etc....

Being upbeat I offer counter arguments to each of your points.  I have seen people suffer n each of the drugs under consideration, but.../font]

Quote
boosted Reyataz potential side effects include increased glucose levels

Unlikely, except as a class effect of PIs if you have the wrong genes, and especially not if combined with tenofovir/Truvada (for obscure reasons)

Quote
potential skin and liver problems

0.3% of people have a serious reaction and unlikely if your viral load is under 50 copies  (but liver worth watching) - nevirapine much under-rated in my opinion.

Quote
If boosted Reyataz fails there's a good chance to lose Kaletra

No. Not a chance.  The mutation sequence for Reyataz resistance is different to Kaletra.

Quote
Intelence -- rash (should manifest quickly) and nausea (always had a very strong stomach)

Who knows, it is likely to be a class effect from NNRTIs so Viramune not a better bet here. But as I said, the proof etc...

Personally, in your position I would be looking at boosted Reyataz and/or Intelence as (you intend, so good)

- matt
Title: Re: Viramune and my doc
Post by: Assurbanipal on May 30, 2008, 08:24:53 pm
Thank you Matt

So helpful! (and reassuring)
Title: Re: Viramune and my doc
Post by: J.R.E. on May 30, 2008, 08:36:12 pm
Hi there,

Whatever is decided, good luck to you. I was started on Viramune, back in October of 2003, and I am still on it. Also, it will be 5 years this coming October. It was also the first regimen I was on. Every three months, my liver function tests, always come back pretty good. The doctor is pleased. I do have some problems with cholesterol. And the HDL/LDL. I never had problems with cholesterol prior to starting on meds, so I do take 10 mgs of lipitor, to try to keep that under control. Started with the cholesterol medication around 7 or 8 months after starting on meds.


Good luck----Ray
Title: Re: Viramune and my doc
Post by: Assurbanipal on May 31, 2008, 12:21:30 pm
Hi Ray
I went on pravachol and it pulled down the cholesterol line as a one time deal when I started but didn't change the upward slope.  Tricor would be the second, plus if the testosterone tests weren't a blip I need to do something there too . . .   So, well, you know, I'm in my fifties and there'll probably be more and more drugs in my future .. .but given I'm lucky enough to still have lots of untried HAART options I figured it might be worth a try to switch regimens rather than keep adding more drugs for cholesterol right now.  Appreciate the good wishes and the Viramune insight and experience.  Hope it keeps working great for you!

A
Title: Re: Viramune and my doc
Post by: J.R.E. on May 31, 2008, 03:58:48 pm
Hi Ray
  So, well, you know, I'm in my fifties and there'll probably be more and more drugs in my future .. .
A

I'm right up there with you too. 56 here. And believe me, I understand what you mean, when you say there will be more drugs in the future ! Hopefully, they will make them more easy to tolerate !!


Take care of yourself---Ray
Title: Re: Viramune and my doc
Post by: deniur efil on June 01, 2008, 07:05:35 am
I think the issue might be the fact that you will be taking 2 drugs that may be liver toxic, apart from the double hit on the liver - if you do have toxicity which drug is causing it or could it be both together.
Title: Re: Viramune and my doc
Post by: Assurbanipal on June 08, 2008, 04:15:28 pm
Quick update -- saw the doc Friday

And the winning HAART combo is ...

more tests (blood and a DEXA scan), an endocrinoligist and if things don't get better maybe we'll swop Kaletra for Reyataz (boosted with Norvir)

Thanks Matt and Peter -- the reyataz option was clearly when we started to have a meeting of the minds.

Assurbanipal