Quantcast

Subscribe to:
POZ magazine
E-newsletters
Join POZ: Facebook MySpace Twitter Pinterest
Tumblr Google+ Flickr MySpace
POZ Personals
Sign In / Join
Username:
Password:
Welcome, Guest. Please login or register.
July 26, 2014, 02:03:28 PM

Login with username, password and session length


Members
Stats
  • Total Posts: 631951
  • Total Topics: 47841
  • Online Today: 250
  • Online Ever: 585
  • (January 07, 2014, 02:31:47 PM)
Users Online

Welcome


Welcome to the POZ/AIDSmeds Community Forums, a round-the-clock discussion area for people with HIV/AIDS, their friends/family/caregivers, and others concerned about HIV/AIDS.  Click on the links below to browse our various forums; scroll down for a glance at the most recent posts; or join in the conversation yourself by registering on the left side of this page.

Privacy Warning:  Please realize that these forums are open to all, and are fully searchable via Google and other search engines. If you are HIV positive and disclose this in our forums, then it is almost the same thing as telling the whole world (or at least the World Wide Web). If this concerns you, then do not use a username or avatar that are self-identifying in any way. We do not allow the deletion of anything you post in these forums, so think before you post.

  • The information shared in these forums, by moderators and members, is designed to complement, not replace, the relationship between an individual and his/her own physician.

  • All members of these forums are, by default, not considered to be licensed medical providers. If otherwise, users must clearly define themselves as such.

  • Forums members must behave at all times with respect and honesty. Posting guidelines, including time-out and banning policies, have been established by the moderators of these forums. Click here for “Am I Infected?” posting guidelines. Click here for posting guidelines pertaining to all other POZ/AIDSmeds community forums.

  • We ask all forums members to provide references for health/medical/scientific information they provide, when it is not a personal experience being discussed. Please provide hyperlinks with full URLs or full citations of published works not available via the Internet. Additionally, all forums members must post information which are true and correct to their knowledge.

  • Product advertisement—including links; banners; editorial content; and clinical trial, study or survey participation—is strictly prohibited by forums members unless permission has been secured from POZ.

To change forums navigation language settings, click here (members only), Register now

Para cambiar sus preferencias de los foros en español, haz clic aquí (sólo miembros), Regístrate ahora

Finished Reading This? You can collapse this or any other box on this page by clicking the symbol in each box.

Author Topic: Viramune and liver toxicity  (Read 1784 times)

0 Members and 1 Guest are viewing this topic.

Offline egello

  • Member
  • Posts: 899
  • cb
Viramune and liver toxicity
« on: August 10, 2012, 04:57:17 PM »
Any scientist type on here that know exactly why (biological reason) Viramune can cause acute liver failure in people who are treatment naive and T cells over 250?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline eric48

  • Member
  • Posts: 1,115
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Re: Viramune and liver toxicity
« Reply #1 on: August 10, 2012, 06:20:51 PM »
No doc on this forum... Patients mostly .

I do take viramune and treatment failure (virologic) had been observed in treatment naives if CD4 over 400 in males and 250 in females.

Hence the screening that is enforced. (this is for treatment naives ONLY).treatment experienced can start viramune regardless of CD4 count 

same thing if VL > 100.000 

Now, this above as nothing to do with liver failure, which is a severe problem but also very rare. This is why viramune users are getting extra blood test for liver enzymes (ALAT, ASAT, ...). There is no way to screen out patients for liver failure or rash s this seems more a multi variable genetic thing rather than some thing that can be easily assessed.

I was initiated on viramune despite the fact that my D4 were in the 500', though...

I was really scared but everything went fine.

Once Viral decay is obtained, viral replication may exist but in such small number of amount that the odds that a resistant variant may occur is virtually zero.

Unfortunately this is not the case during the viral decay phase and a higher number of target CD4s or a higher number of bullets may increase the chance that a a variant may occurs during that phase (hence the failure)

Variability is due to the infidelity of the reverse transcription process.

The NNRTIS (such as Viramune aka NVP, or Efavirenz aka EFV ) block the reverse transcriptase in a geometrical fashion.

To try to explain in layman's word is kind of difficult.

But think like this.

Visualize a hand holding a baseball, then remove the (large) ball.
You hand now has a shape similar to the reverse transcriptase. keep that shape firm

NVP is a small molecule that will geometrically fit between your thumb and first finger, like a small table tennis ball. When the virus DNA approaches the transcriptase, the small ball gets its way. But in some cases it can manage it way through, but not without damage (mutation)

EFV is a larger molecule (like a tennis ball), it fits between the thumb and second finger, thus better blocking transcription process.

More novel NNRTIs are even bigger and fit between thumb and third or even fourth
finger, making a complete blockade.

In this respect they are more 'efficient'

only one mutation during a faulty reverse transcription can make the virus resistant to NVP. EFV requires two mutations. In that respect as well EFV may appear more efficient.

Nonetheless, mutations have a cost on the virus, which becomes less fit for the next round of infection. Efficiency of EFV is superior to that of NVP. but the infectivity of a virus that may have passed the drug (which is not 100% efficient)
is less in case of NVP than in case of EFV

the re-contamination rate is combination of infectivity and efficacy
therefore this combination is similar with NVP than with EFV AS LONG AS the number of rounds and potential events for mutation is not too high (in the case of NVP). IF VL is high or CD4 is high the odds that an unwanted mutation appears increases.

Which is why there is a limitation on NVP initiation on both VL level and CD4 level.
The reason why the cut off value is higher in men than in women is a bit obscure.

It may be related to the fact that proliferation (number of newly created CD4s, hence new 'targets') is higher in women than in men , who, in average have a 100 to 150 higher CD4 count (as observed in the non-HIV infected general population)

The above explanation may have flaws and not scientifically rock solid, but, I hope it helps you...

If you were asking for your self, bear in mind that you are not treatment naive anyway, so that would not apply to you.

If you are asking just out of curiosity, then I hope the above will satisfy you

Cheers! Eric
 

Offline ad2san

  • Member
  • Posts: 184
Re: Viramune and liver toxicity
« Reply #2 on: August 11, 2012, 03:45:06 AM »
Hi Egello, Hi Eric

I totally join the opinion of Eric (my therapy buddy from down under  ;D )
I was also on Reyataz and had to stop after some kidney dysfunction due to Reyataz. I've been on Viramune XR a year now and the results are excellent ! I do have some elevated Gamma-GT and ALAT but doc means it is normal. I draw blood every 3 months.
So far so good. I am much more happy than on Reyataz + norvir; no more yellowing .... and actually I feel great.

Take care guys.
Feb   2009 CD4 358 VL 2000 16%
May  2009 CD4 305 VL 3069  14% <---- Started TVD+ATZ/r
Jul  2009 CD4 512 VL <50   18%
Jul 2010 CD4 418 VL <50 24%                     
Switched to Kivexa (Epzicom) + Norvir + Reyataz (due to sleep problem)
Aug 2010 CD4 606 VL <50 25%
Apr 2011 CD4 523 UD 21%
Jul 2011 CD4 494 UD 23%
Switched to Kivexa (Epzicom) + Viramune XR (due to kidney problems)
January 2012 CD4 564 UD 31%
October 2012 CD4 684 UD 29%
January 2013 CD4 594 UD 26%
Switched to Kivexa (Epzicom) + Isentress due to BIG increase GammaGT
Feb 2013 CD4 699 UD 28%
May 2013 CD4 385 UD 28%
July 2013 CD4 CD4 636 UD 25%
Oct 2013 CD4 588 UD 39%

Offline egello

  • Member
  • Posts: 899
  • cb
Re: Viramune and liver toxicity
« Reply #3 on: August 20, 2012, 12:48:34 AM »
thanks for the replies all, but anyone know the scientific reasons why viramune can cause acute liver failure on a specific group of hiv-ers?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline newt

  • Member
  • Posts: 3,877
  • the one and original newt
Re: Viramune and liver toxicity
« Reply #4 on: August 20, 2012, 09:08:45 AM »
Biochemisty is incomplete, try:

http://dmd.aspetjournals.org/content/37/7/1557.full

for a technical paper highlighting some aspects of the mechanisms involved

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

Offline egello

  • Member
  • Posts: 899
  • cb
Re: Viramune and liver toxicity
« Reply #5 on: August 20, 2012, 10:09:33 AM »
perfect. Thanks Newt
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline eric48

  • Member
  • Posts: 1,115
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Re: Viramune and liver toxicity
« Reply #6 on: August 20, 2012, 04:49:13 PM »
Hi,

severe hepato toxicity, which, we, those who are taking this drug are being monitored for is one thing.

Primary signs would be an significant elevation of ASAT and/or ALAT (aka AST,ALT). ASAT or ALAT would have to be several times the normal range to become a immediate clinical concern.

I was explained so because, once, the biologist, asked me if I knew what to do if ASAT/ALAT go up. I did not ... so I asked my doctor(s)

If severe hepato toxicity shows up, this is a call for action. (and hepatotoxicity is not when your alat/asat are a bit out of range but several times the range value)

It does exist (since I am being monitored for it), yet, and I have no idea of prevalence. Still, I haven't read a recent post of fellow pill buddies mentioning this problem.

it seems to be something that may occur quite early on treatment, eventhough that kind of monitoring is, as this medication, lifetime.

Nevirapine is not the only medication that will require such follow up. Statins (used to lower cholesterol) will require same follow up at initiation.

With Nevirapine being metabolized through the liver, as well as Abacavir (which I take), and recently statin (getting older...) and (aged) red wines , I expressed concerned to my doctor about these too many guys going through my liver. He commented that the liver might be the most resilient organ of all.

I guess, this is because, it rebuilds itself all the time.

Now, (touch wood), 2 years within treatment, I am still within range, so I am not worried, here.

Once again, I think this is something that shows up early into treatment, otherwise you are pretty safe.

For people taking statin (especially rosuvastatin) I have a prevalence number: about 5% adverse hepatotoxicity (as far as I am concerned, so far, so good)

Yet, one less discussed issue is long term toxicity. as the liver rebuilds itself, scars occurs into it and make what is called fibrosis. A primary marker is called FIB4.

Fibrosis is a source of concern this it leads to elevated death risk as shown in the va-cohort follow up study.

My FIB4 was steadily going up, but recently came down to normal (low risk). This seems quite consistent with this:

http://www.ncbi.nlm.nih.gov/pubmed?term=nevirapine%20fib4
Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

and their conclusion: (quote)
Conclusions: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.(end of quote)

In these conclusion, I think we should highlight "in patients who tolerate NVP..."

Nevirapine is a small molecule, so it penetrates everywhere.
Bad news if you are sensitive to it, but good news if you are not.

The only answer is in the trying

Pretty much like every other aspects of NVP: it is either an early failure (rash, hepatoxocity, virological failure...) OR long term efficacy (everytime I meet a doc at the hospital, they always comment that NVP is one of the best (long-term) tolerated drug): I guess it has to do with genetics...

Making life easier for your liver may help too...

May I repeat my question: are you asking this out of general interest and curiosity or do you have a specific concern?

Hope this helps

Eric

Offline eric48

  • Member
  • Posts: 1,115
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Re: Viramune and liver toxicity
« Reply #7 on: August 20, 2012, 05:07:05 PM »
why viramune can cause acute liver failure on a specific group of hiv-ers?

BTW, where do you get that Viramune would cause an acute liver failure on a 'specific' group.

If there was such thing as an identifiable  'specific' group. (as there is for Abacavir...), they would be screened out easily.

There is a  a 'specific' group, who will fail on NVP, but this for virologic failure, not Hepatotoxicity

the article mentionned above:

(http://dmd.aspetjournals.org/content/37/7/1557.full)

ends with :

These findings are significant for understanding the biochemical mechanisms of idiosyncratic toxicity of the reverse transcriptase inhibitor nevirapine.

idiosyncratic is a medical term to say: we have no clue...

Hope this helps

Eric

Offline egello

  • Member
  • Posts: 899
  • cb
Re: Viramune and liver toxicity
« Reply #8 on: August 20, 2012, 06:22:15 PM »
scientific curiosity.
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline eric48

  • Member
  • Posts: 1,115
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Re: Viramune and liver toxicity
« Reply #9 on: August 22, 2012, 07:14:36 PM »
why (biological reason) Viramune can cause acute liver failure in people who are treatment naive and T cells over 250?

???

Out of curiosity, where is it you found that  ???

(I have deleted here a section that was improper, as I did find some relevant info , as you can see below)

Many thanks for your help in this matter and for your contribution to the general interest of those who are considering starting meds (in general) and this one in particular

Eric
« Last Edit: August 22, 2012, 08:41:33 PM by eric48 »

Offline eric48

  • Member
  • Posts: 1,115
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Re: Viramune and liver toxicity
« Reply #10 on: August 22, 2012, 08:37:56 PM »
OOPs

to be exactly correct a quick search on pubmed for words:

nevirapine hepatotoxicity 250

yields a number of answers (about 20). Some of them report hepatotocity in WOMEN with CD4 > 250, some of the reports specify PREGNANT women (which makes it a smaller group) (Brazil, Italy)

Further follow up reports (from resource restricted settings where alternative may not always be available), did not confirm this.(Africa)

One report suggested that hepatotocity would appear mainly in the first year , but not after year 3...(Netherlands)

(conflicting) Reports are coming from various areas of the globe which may reflect either genetics or medical pratice/availability of baseline testing and screening.
(especially baseline testing of ALAT/ASAT, which, IMHO , should be mesured before initiating NVP, but may, for some reason, not be current practice in ome countries)

Wherever reported (and for the small group concerned) prevalence seems to be around 6%

Once my doc mentionned that the limitation on CD4 (250 for women, 400 for men) is being revisited in light on newer less alarming reports. This would be of general interest of clinicians (especially in less rich countries), but, this would have to be initiated by the manufacturer, whose patent is now public domain and may have lost some ecomonical interest in lengthy, controversial research leading to marginal gain in market share.

I do get a high number of PMs by treatment naives who really scared of NVP (and are finally doing fine) that I get a bit personnal about alarming 'information'. Sorry for that.

Hepatotoxicity is observed with a good number of drugs (not only ARVs), but when it gets to ARVs , people are more nervous.

On the funny side, when I initiated Viramune (and Kivexa, not so liver friendly), I had lots of blood test, but also manual examination by my doc.
The only resulting advsere effect was a (noticeable) hard-on , that was nice, but embarrassing. I am quite happy I am done with that...

Hopefully, though, since I am starting statins, I will ask my doc for further 'manual' testing, as, after all, this was part of the fun (and relationship)

Quite sorry for implying this is 'false' information.

In a context of conflicting reports, it hard to navigate.

Cheers Eric



 
« Last Edit: August 22, 2012, 08:45:16 PM by eric48 »

 


Terms of Membership for these forums
 

© 2014 Smart + Strong. All Rights Reserved.   terms of use and your privacy
Smart + Strong® is a registered trademark of CDM Publishing, LLC.