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Author Topic: Once Weekly Dosing Has a Future  (Read 1610 times)

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Offline Central79

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Once Weekly Dosing Has a Future
« on: May 02, 2007, 05:28:03 AM »
I saw this on aidsmap, regarding a type of monoclonal antibody to CCR5 receptors, which would prevent HIV from binding. It's called PRO-140.

http://www.aidsmap.com/en/news/81209316-D51E-4279-B083-5045ACC8A22D.asp

Trial participants showed at least a 10x reduction in their VL, even with the lower dose tried. And it also shows activity to strains of the virus resistant to maraviroc. Although I'm not quite sure how that works.

Additionally, there is a NRTI, elvucitabine, in development that may also only need once-weekly doses. Maybe their will be a cocktail in the near future that allows for less than once daily dosing.

M.
Diagnosed January 2006
26/1/06 - 860 (22%), VL > 500,000
24/4/06 - 820 (24.6%), VL 158,000
13/7/06 - 840 (22%), VL 268,000
1/11/06 - 680 (21%), VL 93,100
29/1/07 - 1,020 (27.5%), VL 46,500
15/5/07 - 1,140 (22.8%), VL not done.
13/10/07 - 759 (23.2%), VL 170,000
6/11/07 - 630 (25%), VL 19,324
14/1/08 - 650 (21%), VL 16,192
15/4/08 - 590 (21%), VL 40, 832

Offline Ann

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Re: Once Weekly Dosing Has a Future
« Reply #1 on: May 02, 2007, 08:11:13 AM »
Now that's what I want to hear! I managed to wait to have my hep C treated until there was once-weekly dosing for the interferon and I'd be over the moon to be able to wait until weekly dosing for hiv is available. I'm crap at taking pills on time and I think I'd have a much better chance with once weekly.

I'm confused about one point though - can this drug be taken as monotherapy? Or do they mean it will be coupled with elvucitabine? The elvucitabine link on the Aidsmap page is broken.

Thanks for the heads-up on this Matt - it's one development I'll definitely be following.

Ann
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Offline milker

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Re: Once Weekly Dosing Has a Future
« Reply #2 on: May 02, 2007, 08:55:35 AM »
That's pretty cool, things are going well in research those days, I feel.

Since it targets one receptor I would imagine that tritherapy is still necessary to avoid the damn resistance?

Milker.
mid-dec: stupid ass
mid-jan: seroconversion
mid-feb: poz
mar 07: cd4 432 (35%) vl 54000
may 07: cd4 399 (28%) vl 27760
jul 07: cd4 403 (26%) vl 99241
oct 07: cd4 353 (24%) vl 29993
jan 08: cd4 332 (26%) vl 33308
mar 08: cd4 392 (23%) vl 75548
jun 08: cd4 325 (27%) vl 45880
oct 08: cd4 197 (20%) vl 154000 <== aids diagnosis
nov 2 08 start Atripla
nov 30 08: cd4 478 (23%) vl 1880 !!!!!!!!!!!!!!!!!!!!!!!!!!
feb 19 09: cd4 398 (24%) vl 430 getting there!
apr 23 09: cd4 604 (29%) vl 50 woohoo :D :D
jul 30 09: cd4 512 (29%) vl undetectable :D :D
may 27 10: cd4 655 (32%) vl undetectable :D :D

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Offline Central79

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Re: Once Weekly Dosing Has a Future
« Reply #3 on: May 03, 2007, 07:20:31 AM »
I'm confused about one point though - can this drug be taken as monotherapy? Or do they mean it will be coupled with elvucitabine? The elvucitabine link on the Aidsmap page is broken.

If you type "elvucitabine" into the search field at the top it will take you to the experimental drugs page, where elvucitabine has an entry.

Although they trialled it initallly with ritonovir they then tried it as monotherapy to work out the contribution it was making to the combo - and it did very well. I would still expect it to be used in combination therapy though - which is why I thought the development of elvucitabine was important, as another drug that could be taken at longer intervals. Definately think its a future possibility.

M.
Diagnosed January 2006
26/1/06 - 860 (22%), VL > 500,000
24/4/06 - 820 (24.6%), VL 158,000
13/7/06 - 840 (22%), VL 268,000
1/11/06 - 680 (21%), VL 93,100
29/1/07 - 1,020 (27.5%), VL 46,500
15/5/07 - 1,140 (22.8%), VL not done.
13/10/07 - 759 (23.2%), VL 170,000
6/11/07 - 630 (25%), VL 19,324
14/1/08 - 650 (21%), VL 16,192
15/4/08 - 590 (21%), VL 40, 832

Offline JPinLA

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Re: Once Weekly Dosing Has a Future
« Reply #4 on: May 03, 2007, 07:39:35 PM »
This is a fantastic possibility and form what I've been reading is very effective especially when combine with other small molecule entry inhibitors like Maraviroc (at least in vitro).  Even as a monotherapy it seems to be a viable option.

I found some of the following information interesting in terms of how PRO 140 works and I am including some of it in my post (how I understand it anyway) as well as links and references to the articles if you're at all interested.  I love this stuff so I really enjoy reading about it.

It seems that PRO 140's attachment to CCR5 does not interfere with the normal function.
 
Unlike small-molecule CCR5 inhibitors which block the  activity of CCR5 PRO 140 doesn't not block CCR5 function "In addition, preliminary studies indicate that PRO 140 is highly active against viruses that are resistant to small-molecule CCR5 antagonists" (quoted from the Murga source). 

They say that the difference is where the small molecules and antibody bind to CCR5. They bind to different part of CCR5 (which they go into some detail about in the paper).  Essentially the small molecule bind to a pocket on CCR5 that is it's active site or allosteric site where as PRO 140 binds to CCR5, doesn't block the active site but does compete out HIV-1 binding.  Very cool.  Means they could be used in tandem and in fact they looked at the synergistic effects and found, at least in vitro, that there was what they considered to be a potent synergistic antiviral effect when PRO 140 and small molecule CCR5 inhibitors were used together.

The little peptide, enfuvirtide, blocks the zippering of glycoprotein 41 which brings the viral and cell membranes together to promote their fusion.  Could be used all together I suppose. 

I'm going to try and attach a schematic of CCR5/HIV-1 interaction because I understand things better with pictures and perhaps you all would benefit from it as well!


Here's to once weekly (maybe biweekly or monthly.....) treatments with low(er) toxicity!

JP

Murga, Franti, Pevear, Maddon, Olson Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1 Antimicrob Agents Chemother. 2006 Oct;50(10):3289-96. PMID: 17005807 [PubMed - indexed for MEDLINE
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17005807
Lederman, Penn-Nicholson, Cho, Mosier Biology of CCR5 and its role in HIV infection and treatment JAMA. 2006 Aug 16;296(7):815-26 http://jama.ama-assn.org/cgi/content/full/296/7/815.


[attachment deleted by admin]
11/06 - Diagnosed - VL/5784 & CD4 326
2/07 - VL/6000 & CD4 290 2/07
3//07 -Began Truvada/Viramune 
4/07 VL/undetectable and CD4 320 22%
7/07 VL/undetectable and CD4 286 22%
11/07 VL/undetectable and CD4 302 26%

 


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