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Author Topic: Resistance In The HIV Envelope?  (Read 2995 times)

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Offline FiercenBed

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  • Posts: 183
Resistance In The HIV Envelope?
« on: February 17, 2007, 04:07:14 PM »
i dont usually get alota replies when i ask complicated questions <cept for newt who gives it a stab; god bless him> but here it goes.

with out retyping the entire history which is available on former post im on my 5th doc. i went to new york for evaluation in a clinical trial but was rejected because of having ks <i cant get a break>. but i did get a through examination <more then current doc> and a free cd4 and vl so it was worth the trip.

anyway @ issue is im in viro failure 1st regime 7 months kaletra & truvada. iv got 2 virtual phenotypes that say no resistance no mutations. iv got 4 docs that say 'i dont know y u wont suppress'. real brain trust here.

so once again i ask the medical director of the program the same tired ol song y wont i suppress w/ no resistance and complete adherence? for some reason i also have low absorption. hez stated that his opinion is that i am resistant to the medication. that the resistance is 'hidding in the HIV envelope' which is not dectalable by geno or phenotypes. it is very rare but he has seen it on occasions. <well im @ least not the only one on the planet> he continues to state that geno and pheno test are not always reliable and 'only give a snap shot' of the situation.

the four other docs act like these test are like a bible for hiv treatment. they should b for what they cost.

anyway herez the question......what the helll is the hiv envelop? iv googled it and it comes back w/ very specific medical gibble goo. none of the other 4 docs have mentioned this. if anyone has heard of this or has a link that is written in understandable english it would b appreciated! i guess on to doc #6.  thanx.
 
« Last Edit: February 17, 2007, 04:09:25 PM by FiercenBed »

Offline newt

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  • the one and original newt
Re: Resistance In The HIV Envelope?
« Reply #1 on: February 18, 2007, 05:02:09 AM »
HIV is made up of several genes, quite a short list really, one of which is called ENV for "envelope".

Wiki entry on HIV genome with handy picture

Most commercial resistance tests don't really look at this gene, they look at mutations affecting reverse transcriptase and protease, the two enzymes most current meds (and all of your meds) are designed to act on.

Some research suggests that mutations in the ENV gene affect resistance, the ability of the virus to reproduce etc etc. ENV is a precursor to gp120 and gp41, two important proteins which enable the virus to attach to and fuse with target cells. Much of the research on the importance of ENV, gp120 and gp41 comes from study of fusion inhibitors.  So the science is fairly new, but reasonably well understood by very expert people and some smart docs.

Suggestion: if your drug absorption is okay, referral to a research centre where they can do sophisticted viral analysis, eg British Columbia, Stanford, Mayo etc.  Or rather, send your blood there. If not okay, get this sorted first.

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

Offline FiercenBed

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  • Posts: 183
Re: Resistance In The HIV Envelope?
« Reply #2 on: February 18, 2007, 02:24:03 PM »
i shoulda known....lol. i was just gonna send ya a pm but thought that was intrusive. jeesh is this stuff fucked up or what! i dont know what the repercussions r yet, but itz nice to have a direction to go in and as i said that im not the only person on the planet w/this problem.

itz gonna be an interesting conversation w/ my doc on this one. letz c how much the man knows.

Offline bimazek

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Re: Resistance In The HIV Envelope?
« Reply #3 on: February 25, 2007, 07:42:32 PM »
http://www.roche-hiv.com/roche-in-hiv/Resistance.cfm?link=Resistance

check out this detailed
roche

resistance

somethings i got from it are... perhaps the drug is not being absorbed, can a person tolerate higher doses, or new combos


Offline HIVworker

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  • Posts: 918
  • HIV researcher
Re: Resistance In The HIV Envelope?
« Reply #4 on: February 26, 2007, 09:27:35 PM »
I don't get this. How can resistance to these two drugs be in the envelope? I've seen mutations in the cytoplasmic tail that speed up the fusion process because the virus lacks any communication with the capsid (supposed to slow things down) but nothing I have seen affects resistance to RT inhibitors.

There are resistance tests available for the Env. Labcorp has one http://www.labcorp.com/services/hcp/hiv/index.html. I'd be surprised if nobody offered a Env genotype or phenotype test given that you get T-20 resistance mutations in Env. If they are not widely available they will be soon as maraviroc is coming on line.

I studied Env proteins for 5 years. If I can help out, let me know.

Rich
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline jjmcm

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Re: Resistance In The HIV Envelope?
« Reply #5 on: February 27, 2007, 08:51:06 AM »
While I know it is frustrating dealing with an unsuppressed virus, I did so successfully for nine years on treatment.  My first VL test in 1996 was around 1 million.  After changing therapies my virus would stay low and then slowly work itself back up to several hundred thousand.  The majority of the time my CD4's stayed in the 200-400 range.  Because of this and the lack of medication to adequately suppress my virus, my doctor allowed the VL increases until we had a new regimen to switch to.

In the fall of '05, with my VL at 700,000+ and my CD4’s crashing down to just below 100, I started Kaletra tablets (125%), Invirase, Combivir (Yuuuukkkk!) and Fuzeon.  My doctor also talked me into a couple of nasty weeks on an IV of Foscarnet to help beat the virus down.

This finally worked and my VL has been under 50 for over a year.  Perhaps it is strange to have this happen to you on your first regimen.  However, it does happen from time to time and your only choice is to keep the faith that you will find something that works.

I did and it took a long time to get it right…

Offline FiercenBed

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  • Posts: 183
Re: Resistance In The HIV Envelope?
« Reply #6 on: February 27, 2007, 06:32:40 PM »
hey hivworker.....u sound like my primary doc.....he doesn't get it either. but like i told him....i cant make this stuff up. the new york doc has been the first doc to offer a possible suggestion other then the usual "i don't know." not only is this new york doc in2 hiv but also genealogy so that adds some credibility for me.

iv read some some hiv cmes on resistance. therez a statement:

There have, however, been isolated case reports of patients failing first-line therapy with lopinavir/ritonavir[9,10] or fosamprenavir/ritonavir[11] . The infrequency of these case reports highlight the rarity of this phenomenon; therefore, they appear to be the “exception to the rule.”

so great im the exception to the rule. iv got 2 of those $600 Genosure test that states no resistance no mutations. there 6 months apart. the good news if there is any my recent vl dropped from 2,500 to 487.
so 160,000 to 410 to 4000 to 2500 to 487 all w/out change in meds. doc definitely sez these arnt 'blips'

i FINALLY got my doc to agree to call the doc in new york to c what particular the deal is. hez been a dick head about calling anyone for outside consultation. wont call nih, wont call abbott so in my opinion this is a good first step!


Offline HIVworker

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  • Posts: 918
  • HIV researcher
Re: Resistance In The HIV Envelope?
« Reply #7 on: February 28, 2007, 12:21:28 AM »
Just one thing to check. Have you been having a standard RT genotype assay as that covers only the first 300 or so amino acids of RT. There are resistance mutations outside this area in RT that aren't covered by that assay. You might want to look into getting the whole RT sequenced to see if there is anything going on in the latter regions of RT. There have been novel resistance mutations described in this area, although they mainly augment NRTI and NNRTI resistance they do actually confer some resistance themselves. It could be that due to your low absorbance of the drugs they are not reaching a desired PK and any putative C-terminal RT mutations are impacting the resistance.

Something to consider. It's just a thought and I'd go with your ID doctors advice. Mention it to him though, and get him to read up on C-terminal RT mutations that aren't covered by standard genotype assays.

Did you have a phenotype test too? If you had a standard phenotype assay I'd expect that to not show resistance if this off-the-wall idea has any substance...

Rich
« Last Edit: February 28, 2007, 12:25:20 AM by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

 


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