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My Antiretroviral Trial

Rrrr

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can you tell us, are you experiencing ANY side effects from the meds?

also, would you describe yourself as a person who is hyper sensitive to most meds, as many of us with ME/CFS are?

best
rrrr
 

mojoey

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Leaves,

Indinavir has however been shown to inhibit MLV: http://jvi.asm.org/cgi/content/full/73/10/8813
The results obtained indicate that the combination of nucleoside analogs zidovudine and dideoxyinosine with the protease inhibitor indinavir effectively inhibits MLV-derived RCR replication in three human cell lines.
I wouldn't discount Jake's experience with this drug.

I'm guessing that we'll just need to wait to have more protease inhibitors developed instead of using the HIV ones, because this study found that even when they did work for MLV, they were much less potent than for HIV: http://vir.sgmjournals.org/cgi/reprint/87/5/1321.pdf

Inhibitors designed against HIV-1 PR were also active on MLV PR,
although all of the tested ones were substantially less potent on this enzyme than on HIV-1 PR.
Nevertheless, amprenavir, the most potent inhibitor against MLV PR, was also able to block
Gag processing in MLV-infected cells.
Note: amprenavir is no longer on the market.
 

Megan

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Jake,

Thanks for posting your experience with ARV's.

I am interested in following all those trying ARV's but I find it somewhat confusing to try and interpret results unless I know their XMRV status.

I am assuming you were tested for XMRV? If so, are you able to share what tests you had done and what the results were? If not please let us know too.

thanks,

Megan
 
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Hey guys,

I have found that upon starting the meds my main side effect has been slight nausea, it's uncomfortable, but not nearly enough to make me regurgitate. I also have had a few more chest (heart) pains than usual, however I've had this prior to taking the ARV's as many PWC's do, and I know from testing that my blood gets very viscose, so I have been taking aspirin for it (75-150mg enteric coated) - this helps a great deal.

Some people have asked about any hypersensitivity in general to meds. I wouldn't necessarily say I am that overly sensitive, however I did get a very bad reaction initially to doxycycline (most probably lyme herx?), citalopram and vitamin D. So it seems to vary. These made me go incredibly weak and irritable along with exacerbated sensory overload.

Just to remind you all that I am NOT XMRV positive (so far). My culture test showed up negative. I am currently awaiting results of the new antibody test.

My whole intention with trying the protease class of ARV's is that I could well be infected with a CFS type 1-4 MLV virus, as identified in the alter paper, for which Indinavir is shown to be effective.

What I find most promising is that there are at least several protease inhibitors already approved for HIV infection that were approved by the FDA years after the following paper was published in October of 1999. Some of which have improved side effect profiles.

Jake
 
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Thanks mjoey for finding that paper.

That is very interesting. It seems from studies so far that the majority of these ARV's are less potent against XMRV/MLV's than they are for HIV. The findings of the singh study confirm this, with AZT and Tenofovir being less potent. However raltegravir seems to be the exception, quite possibly being more potent that against HIV I recall?

It's unfortunate that amprenavir is no longer on the market. However GSK have made the prodrug available which ultimately would results in the same biochemical effect. See: http://en.wikipedia.org/wiki/Fosamprenavir

As these drugs have not been designed specifically with XMRV/MLV replication enzymes as the protein target, it's not surprising they are less potent. However a combination of these, possibly protease inhibitors might still account for significant improvement. The main worry is that if they are less potent, drug resistance is more likely to occur, which would render some of these meds useless. I don't know how you can overcome this problem other than dose modification and using a cytochrome P450 CYP3A4 inhibitor such as ritonavir in conjunction.

Jake
 
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Hey all,

Yesterday during the day I experienced a bit of a dip. I felt rather worn out (very tired, but not in any way wired - this is a big change for me) and so went and had a 2 hour lie down. However, later that evening I felt significantly better, so much more energy and strength in my body, I actually felt to my amazement quite euphoric. I think this is because I have forgotten what it is like to feel near normal. It was just incredible to be able to get out of the bath without feeling like your limbs do not respond. Also a big change I noticed was much improved circulation of my skin. (normally my chest and abdomen are chillingly cold!)

Today during the day I had less strength than as of last night, but overall I still feel noticeably better than before commencing HAART.
 

Rrrr

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fantastic! just what we wanted to hear. keep up the good work of being our human guinea pig (or lab mouse, as the case may be).
 
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Hi Jake,

I will be going on ARV's at the end of this month, and I am glad to see someone else considerring PI's. After much research on which combination of AVR classes are available that have a good sucess rate with HIV, and after determining that Raltegravir is not within my financial means, and after consultation, I deduced that my trial might consist of AZT, Tenofovir and Sustiva (Efavirenz), a PI. These are the ones I can afford, so is what I will be going for initially.

EDIT: I did check on Humana's drug list, and Crixivan is coverred as a tier 2 drug. That is good news. I am interested if you know, if the difference between sustiva and crixivan are significant? If not, I'll go forth and try and ascertain. :+)

But, I also want to get as informed as possible again before I meed with my doc. SO, thank you for posting and updating us!

Hope to hear more from you,

~ katieann
 

Daffodil

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hi katie....can i ask where you heard Sustiva would be affective against XMRV? i cannot find this info anywhere.

also, i think you can get RAL free from the drug co. if you are eligible

best of luck! fingers crosssed

xoxoxo
sue
 
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Sustiva is not a PI and would not be indicated at all. It has some significant psychiatric adverse effects and should be avoided. It appears to have essentially no activity against X in vitro.

Jamie Deckoff-Jones MD
 
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I think many of us will have to settle for just the two drugs , either because Isentress is so costly or because we cannot get a perscription. I would like to take all three but I cannot find a place on line to sell Isentress without a perscription. Dr J., are you taking on any private patients at the moment ? Peter Miller.
 
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Why in the world are you taking antivirals if you haven't even confirmed the diagnosis and that the viral copy number isn't decreasing? Haven't results for anti-viral therapy on fatigue been mediocre so far? I don't know why everyone is so keen on antivirals given the low copy number.
 

ukxmrv

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Go back and read this thread from the start, please Fejal.

This patient is willing to experiment. It's their decision. Why are you so hard on people trying treatments other than the theory you are pushing?

(start)
My whole intention with trying the protease class of ARV's is that I could well be infected with a CFS type 1-4 MLV virus, as identified in the alter paper, for which Indinavir is shown to be effective.
(end)
 

mojoey

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The low copy number is precisely why an active protease inhibitor (one that works on XMRV and MLVs) is necessary. It can very well be that most of the damage is caused by the integrated DNA continually spewing out viral proteins.

You need to understand that "antivirals" covers the whole lifecycle of a retrovirus, in theory. In practice, it has leaned toward preventing reverse transcription and host genome integration because HIV is a fast replicator. In theory, any drug that prevents damage from the retrovirus by working directly on the retrovirus is considered an antiviral. Therefore your outright dismissal of antivirals for gammaretroviruses makes no sense. We're gonna have to tweak the protocol a bunch of times before we get it right, so I applaud anyone who's brave enough to take the plunge as long as it's well thought through