Is Marivaroc safe for formulating a new combination

[ZCorker]

  I am currently Kaletra and Viread and over 9 months ago had to give up 3tc and T-20 due to intolerance.  My T-Cells have slipped from 540 to 348 and viral load is running about 27,000.  I am planning on starting a new regimen this fall and would like to know if Marivaroc is safe?

  I am a heavly treatment experienced hiv patient with the L10 mutation to protease inhibitors. I have high level resistance to everything except the two drugs that I am on and have moderate resistance to these drugs as of November 2005.

   I would like to formulate a new combination and was wondering what would be  a workable combination?  I thought about the following:

    TMC 125
    Merk Integrase Inhibitor
    Tanox 355
    TMC 114
    Marivaroc

   
    Is Marivaroc Safe?  What are its side affects?  How hard is it on the liver?
 I am currently suffering from dangerously low HDL and blood sugar over 100.  I am trying to get someone to give me a low dose of Actos, but no doctor in SEattle will give it to me.  I have a sunken face that looks like draculate and obstructive apnea that is so bad that I have to sleep on five pillows "with a machine".  The machine is only minimally beneficial from the atrophy.   I have found some things in the literature that seem to indicate that low Blood Serum Adiponectin is associated with apnea in many patients and Actos should help me.

   Has anyone taken Marivaroc on here?   Any one had side affects?   Drop me a line and let me know.  I no longer post my e-mail on here due to spam, but you can ICQ me and I will e-mail you back.  My ICQ number is 118179171.

[SirPrize]

MARAVIROC (UK-427,857) is an investigational medicine that is not yet approved by the FDA for use outside of clinical trials. It is being studied for the prevention and treatment of HIV infection.  Use the link below to learn more about the drug.



http://www.aidsinfo.nih.gov/DrugsNew/DrugDetailNT.aspx?MenuItem=Drugs&Search=On&int_id=408

[ZCorker]

  I am well aware that Marivaroc is an investigational drug not approved by the FDA and that is the reason that I am posting this question.  Again I will ask whether or not anyone on here has taken the drug or has experience using this medication.   

   Just because something isn't approved by the FDA doesn't mean the medication isn't any good.  On the other hand, just because a medication is approved by the FDA doesn't mean the drug is worth taking.  Tipranavir and D4T are two good examples of drugs with serious problems, but they are FDA approved.

   I am looking for peoples personal experiences or comments they have heard in the community -- not a statistical analysis of what is approved by the FDA.  I am fully resistant to all medications and have limited sensitivity to the two medications that I am on -- Kaletra and Viread.  Making an informed choice is a life and death decision and not to be played with.

   

[penguin]

Z,
Ive been following stuff on maraviroc, just cos, well, it’s new & shiny, & my drug wardrobe, is looking a little bare these days.

In terms of safety, it looks good so far. One case of liver toxicity in over 1000 people, & that was probably combo of pre-existing liver issues & concomitant meds anyways.
Cardiovascular effects look minimal so far too, a few postural hypotension reports, but other than that, some nausea etc, nothing major.

as I understand it, people with CCR5-tropic virus proabably gonna get better virological results than people with CXCR4-tropic or dual/mixed-tropic.  If think if this was me, one of my worries about taking this drug now, when it is still so new, would be uncertainty about the longer-term consequences of blocking R5 receptors/having X4 end up as dominant. So far though it doesn’t appear to have caused any problems..

Tmc 114, is one of my combo,been ok with side effects, much better than other meds.

 MK-0518 looks impressive too…

The “intolerance” to t-20 & 3tc was…?

kate

[ZCorker]

  Good morning Penguin.  It is so nice to have someone to talk to about this stuff -- even if it is in the virtual world.  I feel comfortable with the Merck Integrase Inhibitor and believe it would be a better option than the Gilead Sciences Inhibitor if I am planning on taking TMC 114?  I already have the L10 mutation so benefit from TMC 114 is going to be questionable.

  Has any data been reported on CCR5 virus actually switching to CCR4 in patients on Marivaroc?  Another concern about Marivaroc is increased sensitivity to Nile Virus Infection.  Most people are probably ok if they live on the west coast, but anyone in the south would be very high risk.

  I do recall reading that you can mix fusion inhibitors and actually get a better result and I am wondering if mixing Tanox 355 and Marivaroc in combination with TMC 125 and MK 0518 would be an option for me?  I am wondering how hard this combination is on the liver?  Tanox 355 blocks both CCR5 and CCR4.  However, patients that have taken it developed resistance quickly.  It is definitely not a drug you want to take alone.

  Around the Seattle Area some of the  physicians who hold credentials from the hiv medicine association have never heard of either Marivaroc or Tanox 355 and didn't seem to accomodating about getting me either drug.  This concerns me because this may very well be my last chance to go undetectable.  I don't want to blow it. 

  I am well on my way to becoming diabetic and really need to start Actos.  I have all of the classic symptoms -- severely sunken face, blood sugar >100, Triglycerides >150, and dangerously low HDL.  I have been taking 1000mg of Niacin to propup the HDL, but I am loosing control and the HDL slipped to 37 on the last blood test.  Without the Niacin I would be in the low 20s.  I don't have any history of having this type of problem and believe the low HDL is caused strictly from insulin resistance.  Prior to starting protease in the mid 90s, my HDL was 44.  I am concerned that the Niacin may be increasing the blood sugar.  The literature does not recommend Niacin if you have insulin resistance.

   

 

[Customer]

You suggested:

TMC 125 (NNRTI)
Merk Integrase Inhibitor
Tanox 355
TMC 114 (PI)
Marivaroc
---



If L10 mutation exhibits resistance to also TMC114 then you can count that one out. On the other hand, if it does not, then take it in combination with a conventional PI which your HIV-virus already has resistance against. But i do not know if L10 exhibits resistance to TMC114

I think there is synergy between

Maraviroc (CCR5 blocker)
Tanox 355 (CD4 blocker)

Be sure to have them both. Add Fuzeon to it if you can afford it, regardless of whether you have resistance to Fuzeon or not. These 3 would make a combination entry phase inhibitor. Do not take TNX355 as solo entry inhibitor.

If you skip TMC114, then go for  Merks Integrase Inhibitor.

[jjmcm]

I just attended a seminar in Houston that Nelson Vergel was speaking at.  (I am currently on Kaletra, Invirase, Combivir, and Fuzeon.  It is the first time in ten years I have been undetectable.)

It seems of all the meds you are considering, the absolute "must have" would be the Merck Integrase.  It may be the strongest medication yet from the results.  You can get it now in expanded access and most patients find it very effective.  Personally, I would get that.

If you choose it though, you have to forego TMC 125, they are not allowing that mix yet. 

I would bypass Maravaroc for now.  There seems to be a lot of unknowns about the side effects which could be greater than is currently known. 

I don't think you will need to mess with Tanox if you get the Merck Integrase.  Tanox is a pain and really only shows limited benefits.

I am also curious about your intolerance to Fuzeon.  I take it and it is literally a pain.  But, it has probably saved my life.

TMC 114 might still be a good choice.  You could consider adding another PI to it.   I doubt you would have a VL right now if you had been on Invirase in addition to Kaletra and been able to stay on Fuzeon.  It is a strong combo and used frequently in our area for salvage.

Good Luck,

--JJ 

[Rusty]

I am currently taking Tipranivir, Ritonavir, Viread, Combivir and T20.
I am looking to change my meds in December as the T20 is not ideal for me to take now and is quite painful and the Tipranivir can cause bleeds in the brain so I am not keen to stay on that. I have been on this combo for 18 months with good results.
I am switching to TMC 114, TMC 125 still using Ritonavir as a booster with Viread & Combivir.

The TMC drugs are supposed to be very good , will let you know.

[ZCorker]

  I was on T-20 for over 4.5 years and finally had to go off of it.  It left me with permanent damage to the skin area on the upper sides of my thighs; kind of like a permanent thickness in the skin.  I was finally taken off of it when I was advised that I had developed resistance mutations that indicate the drug was no longer of any benefit.

   Several months later and late this past spring, new data emerged that indicates that there was virological suppresion with T-20 -- even when the resistant mutations emerged.

   I have been advised that the L-10 mutation is an indication that I probably will be resistant to all protease.  However, TMC 114 is a strong drug and I will probably have some benefit from it.  Although Tanox 355 is a weak medication, it does block both CCR4 and CCR5 site and I read a report earlier that indicates it can be taken in combination with Marivaroc.  I was wondering if anyone has any information on that?  I don't have a lot of options and can't tolerate D4T, DDI, DDC, or 3TC.  Hopefully someone on here will be able to post some information about their experience with Marivaroc.