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Author Topic: Gilead's tenofovir prodrug GS 7340  (Read 7772 times)

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Offline xman

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Gilead's tenofovir prodrug GS 7340
« on: April 10, 2012, 02:56:55 pm »
i was reading about the potential of this new drug actually in development by gilead which will replace the current version of tenofovir. it seems that it is 200 times more active in lymph nodes and other tissues than the most powerful drug available today. if this is indeed the case this new drug could have an important role for future eradication trials since it is more able to reach those cells in which current haart is unable to go. there's an article from the last croi mentioning this potential and the possibilities of this drug to accelerate the research for curing the disease.

Offline buginme2

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #1 on: April 10, 2012, 03:07:50 pm »
Why don't you post a link to the article?
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Offline xman

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #2 on: April 10, 2012, 03:10:45 pm »
http://www.projectinform.org/news/pathway-to-a-cure-viral-eradication-and-control-research-from-croi/

(Not so) Complete Viral Suppression

One of the great hopes about the integrase inhibitor raltegravir (Isentress) or the CCR5-blocking drug maraviroc (Selzentry) was that we might be able to add one or both to a fully suppressive ARV regimen and in doing so help diminish the pool of latent and hidden HIV. Unfortunately, nearly every study to date of this strategy, called treatment intensification, has been an utter failure. Robert Siliciano has presented data showing that HIV suppression by most currently popular drugs is likely to be so effective (at least in blood) that it would be difficult to improve upon them. Some experts have wondered, however, whether “fully suppressive” ARVs are actually completely suppressing HIV everywhere that it lives within the body.

To add weight to that argument, Courtney Fletcher from the University of Nebraska reviewed data he had previously presented on the penetration of commonly used ARVs into some of the compartments that experts believe are crucial hiding places for HIV.  Fletcher’s presentation offered a compelling explanation for why ARV intensification studies have so far been utter failures—if the additional drugs we pile onto a suppressive regimen don’t go where they need to there’s little hope that they can reduce the reservoir of infected cells.

Fletcher used childhood leukemia as a model to explain his motivation to understand ARV penetration into various tissues. The first effective treatments for childhood leukemia involved combinations of toxic drugs that were only minimally effective, whereas today we use therapies and procedures that direct very specifically targeted drugs where they need to go and achieve nearly 90% cure-rates. His unanswered question is where along that spectrum are we with HIV?

Fletcher talked about studies he and others have conducted for where various ARV drugs go and the concentrations of those drugs into those biological compartments. One of his most striking findings was that almost none of the current crop of ARVs penetrates very effectively into two of the sanctuary sites thought to harbor the majority of latent HIV: lymph nodes and gut-associated lymphoid tissue (GALT).

Fletcher ended on a slightly optimistic note, however, by showing data on two special formulations of existing HIV drugs that do go exactly where they are most needed, the drugs being atazanavir (Reyataz), a protease inhibitor, and the drug tenofovir disoproxil fumerate (TDF), commonly sold as Viread. Fletcher reported that a nano-formulation of atazanavir and a new specially formulated version of TDF called GS-7340, have excellent penetration into the lymph system whereas their parent drugs don’t go there at all. Such specialty formulations, he theorized, could give a substantial boost to our efforts to eradicate HIV.
« Last Edit: April 10, 2012, 06:04:23 pm by xman »

Offline Hellraiser

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #3 on: April 10, 2012, 03:25:38 pm »
Nice article X-man.

Offline younghopefulpoz

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #4 on: April 12, 2012, 02:08:23 am »
I'm hoping for this to come for a cure :)

Offline Ann

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #5 on: April 12, 2012, 07:20:25 am »
Hell, I don't really give a shit if it is a cure, I'd just be happy if these two new formulations did something to fix my hiv-related diarrhea.

My hiv doctor (who is also a renown hiv pharmacologist) theorises that hiv in my GALT is what's behind the problem - and why he does not believe that going on treatment would change things (and may even make it worse). I'll have to ask him what he knows about the new formulations the next time I see him.

According to the page on GS-7340 in our Treatments section, the dose for GS-7340 is ten times lower than for Viread.

In early Phase II studies, researchers identified a GS 7340 dose that is ten times lower than Viread and provides greater antiviral efficacy. The smaller milligram size of GS 7340 should enable the development of new fixed-dose combinations and single-tablet regimens for HIV therapy that are not feasible with Viread.
             
Two advanced Phase II studies of GS 7340, as a part of fixed-dose combination tablets, have been a announced by the company. One such tablet contains GS 7340, Emtriva (emtricitabine), the novel booster cobicistat and the experimental integrase inhibitor elvitegravir. A second tablet, being developed in conjunction with Janssen Therapeutics, contains GS 7340, emtricitabine, cobicistat and the protease inhibitor Prezista. 


I'm kinda disappointed that they're not looking at it in combination with Reyataz. On the other hand, it's good to know that the new formulation is such a low dose - it might help prevent the possible bone density, cholesterol and triglycerides, and kidney problems associated with Viread.

We don't seem to have a page covering the new formulation of Reyataz - I'll have to poke Tim Horn and ask him what's up with that. ;D 
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

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HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline Miss Philicia

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #6 on: April 12, 2012, 03:10:05 pm »

We don't seem to have a page covering the new formulation of Reyataz - I'll have to poke Tim Horn and ask him what's up with that. ;D 

I read about it somewhere months ago -- and even put not one but two posts about it.

edit: http://www.poz.com/articles/hiv_7340_tenofovir_761_22087.shtml

http://www.aidsmeds.com/archive/GS7340_2691.shtml

Please keep up

ps: this drug was developed IIRC in 1995 but then sat on a shelf -- helps that Viread is going off patent: http://aac.asm.org/content/49/5/1898
« Last Edit: April 12, 2012, 03:16:57 pm by Miss Philicia »
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Offline mdh26

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #7 on: April 12, 2012, 06:24:20 pm »
Would you need a complete combo that goes into the lymph nodes to use either of these drugs? I suspect that not having that in place would lead to resistance issues since you'll have only viread, for instance, attacking the hiv in the lymph nodes. And when that mutates around it, the resistant virus will spread to the rest of the body.

Offline Ann

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #8 on: April 13, 2012, 01:35:10 am »
I read about it somewhere months ago -- and even put not one but two posts about it.

edit: http://www.poz.com/articles/hiv_7340_tenofovir_761_22087.shtml

http://www.aidsmeds.com/archive/GS7340_2691.shtml

Please keep up

ps: this drug was developed IIRC in 1995 but then sat on a shelf -- helps that Viread is going off patent: http://aac.asm.org/content/49/5/1898

Epic fail.

"Please keep up" yourself, Miss PeePeePantiesInAWad. I said...


We don't seem to have a page covering the new formulation of Reyataz - I'll have to poke Tim Horn and ask him what's up with that. ;D 


I'd already posted the link to our drug information on GS-7340 - the new formulation of Viread. There is no such page on the new formulation of Reyataz mentioned in the article Xman posted.
Condoms are a girl's best friend

Condom and Lube Info  

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline Tim Horn

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #9 on: April 13, 2012, 07:22:43 am »
There is no such page on the new formulation of Reyataz mentioned in the article Xman posted.

Still just a test tube compound and a dream! BMS and a few others are tinkering with nanotechnology to improve tissue concentrations of various ARVs. And I promise, once Nanotaz has something to show for itself, it'll be on the site  ;D

Offline Ann

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #10 on: April 13, 2012, 07:30:31 am »
Still just a test tube compound and a dream! BMS and a few others are tinkering with nanotechnology to improve tissue concentrations of various ARVs. And I promise, once Nanotaz has something to show for itself, it'll be on the site  ;D

Thanks Tim! I was going to poke you about that today - and I was expecting the explanation you gave. Just wanted to pick your brains about it a bit while we were at it. :)
Condoms are a girl's best friend

Condom and Lube Info  

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline Miss Philicia

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Re: Gilead's tenofovir prodrug GS 7340
« Reply #11 on: April 13, 2012, 07:38:30 pm »
sure
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