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Author Topic: Truvada and Viramune Combo Question  (Read 1942 times)

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Offline egello

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Truvada and Viramune Combo Question
« on: March 26, 2010, 04:04:56 AM »
I don't get this combo...

Isn't Viramune a NNRTI and doesnt' Turvada contain both NNRTI and NRTI? So why take supplemental  extra NNRTI with Viramune?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline newt

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Re: Truvada and Viramune Combo Question
« Reply #1 on: March 26, 2010, 05:32:02 AM »
Viramune is an NNRTI (non-nucleoside reverse transcriptase inhibitor).

Truvada contains two RTIs (the nucleoside reverse transcriptase inhibitor called emtracitabine and the nucleotide reverse transcriptase inhibitor called tenofovir).

This meets the requirement for 3 drugs from at least 2 different classes needed for a standard combination.

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

Offline Inchlingblue

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Re: Truvada and Viramune Combo Question
« Reply #2 on: March 26, 2010, 11:41:39 AM »

Truvada contains two RTIs (the nucleoside reverse transcriptase inhibitor called emtracitabine and the nucleotide reverse transcriptase inhibitor called tenofovir).


I know it was a typo but just so it's clear, Truvada contains two NRTIs.

Offline egello

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Re: Truvada and Viramune Combo Question
« Reply #3 on: March 26, 2010, 11:50:59 AM »
ah.. thanks for the info

But i wonder why two different drugs from the same class is recommended instead of say doubling the dosage of just one instead...


Also, anyone know what it means by non-nucleoside? I know what nucleoside is, but when NNRTI is specific to non nuceloside rti, what mechanism is it referring to?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline newt

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Re: Truvada and Viramune Combo Question
« Reply #4 on: March 26, 2010, 01:39:10 PM »
Quote
I know it was a typo but just so it's clear, Truvada contains two NRTIs.

To be really nerdy about it, it's not a typo, tenofovir is a nucleotide inhibitor not a nucleoside inhibitor. The difference is probably only important to a chemist.

Egello, 2 different classes are recommended so that  the drugs attack the virus at two points in its lifecycle. This helps prevent resistance.

You can see where different drugs interact with HIV at the link below:

http://i-base.info/guides/starting/hiv-lifecycle

While all the drugs in your combo attack the virus at the reverse transcription part of its lifecycle, they are sufficiently different to count as two separate drug classes. Reverse transcription is the process where HIV uses its RNA and an enzyme (reverse transcriptase) to make DNA for new viruses.

As to the name, the drugs interefere with ithe enzyme reverse transcriptase, hence "reverse transcripase inhibitor". The "nucleoside/nucleotide/non-nucleoside" part describes the general chemcial character of the drug.

Hope this helps.

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

Offline egello

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Re: Truvada and Viramune Combo Question
« Reply #5 on: March 26, 2010, 02:00:40 PM »
Thanks Matt

But I was wondering why does Truvada contain two same class drugs instead of doubling the dosage of just one?

How do those two NRTIs contained in Truvada differ from each other?

Also, if Tenofivir interferes with building material nucleotides, then would it interfere with other normal bodily DNA building mechanism?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline Inchlingblue

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Re: Truvada and Viramune Combo Question
« Reply #6 on: March 26, 2010, 05:06:40 PM »
To be really nerdy about it, it's not a typo, tenofovir is a nucleotide inhibitor not a nucleoside inhibitor. The difference is probably only important to a chemist.

 


Technically you're right and I can understand why you'd to leave out the N but I don't think it's standard. When you have a nucleoside and a nucleotide reverse transcriptase inhibitor together, such as in Truvada, since they're both "nukes" they're just referred to as NRTIs (I guess for expedience).
 
I have seen nucleotide reverse transcriptase inhibitor sometimes referred to as NtRTI if you wanna get technical about it ;)

LINK:

http://www.aidsmeds.com/archive/NRTIs_1082.shtml

http://www.truvada.com/

PS: I'm not trying to be pedantic, I just thought RTI looked confusing.
« Last Edit: March 26, 2010, 06:14:24 PM by Inchlingblue »

Offline Inchlingblue

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Re: Truvada and Viramune Combo Question
« Reply #7 on: March 26, 2010, 05:23:55 PM »
But I was wondering why does Truvada contain two same class drugs instead of doubling the dosage of just one?

How do those two NRTIs contained in Truvada differ from each other?

Also, if Tenofivir interferes with building material nucleotides, then would it interfere with other normal bodily DNA building mechanism?

As far as combining nukes, whether nucleoside or nucleotide, as Newt mentions it's important that the drugs be different enough from each other, meaning in terms of their resistance profile and their barrier to resistance. Viread and Emtriva together work well, whereas, for example Viread and Epivir are too similar and would not work well together.

There was a recent question on Gallant's site that might shed some light:

http://www.hopkins-hivguide.org/q_a/patient/antiretroviral_therapy/antiretroviral_agents/nucleoside_and_nucleotide_reverse_transcriptase_inhibit/new_nrti_combination_.html?contentInstanceId=516879&siteId=7151
« Last Edit: March 26, 2010, 05:53:34 PM by Inchlingblue »

Offline Assurbanipal

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Re: Truvada and Viramune Combo Question
« Reply #8 on: March 26, 2010, 05:48:40 PM »
Maybe the videos on this page would be helpful Egello

http://www.boehringer-ingelheim.com/news/media_material/image_videos/indication_areas.html#tabs-1-2

The third one is just about how the NRTI's  and NNRTI's work

The first talks about the ways the various different drug classes work adding the fusion, integrase, protease and maturation inhibitors as well. 

They were a little visually busy and confusing the first time through (for me at least -- not a visual type).  Still they were helpful the second time

A
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline ATorrez

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Re: Truvada and Viramune Combo Question
« Reply #9 on: March 26, 2010, 05:50:23 PM »
Actually, Viread and Epivir are not similar. Epivir and Emtriva are. Although I am sure it was just a typo.
Piss off a democrat: Take responsibility for your life and your actions.

"When Marxist dictators shoot their way into power in Central America, the San Francisco Democrats don't blame the guerrillas and their Soviet allies. They blame United States policies of 100 years ago. But then they always blame America first." -Jeanne Kirkpatrick

Offline Inchlingblue

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Re: Truvada and Viramune Combo Question
« Reply #10 on: March 26, 2010, 05:59:24 PM »
Actually, Viread and Epivir are not similar. Epivir and Emtriva are. Although I am sure it was just a typo.

Yes, thanks for catching that! All those different names can get confusing. To quote Gallant in above link:

Emtricitabine and lamivudine are virtually the same drug.

« Last Edit: March 26, 2010, 06:32:09 PM by Inchlingblue »

Offline egello

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Re: Truvada and Viramune Combo Question
« Reply #11 on: March 26, 2010, 06:58:40 PM »
wow, that was really helpful

some questions that arose while watching the video..

What happens to the RNA and DNA of HIV that do not go through intergrasing with the human DNA, or Fuse with the host cells? do they just get broken down or die off? it seems like the meds prevents different parts of the replication cycle but does not actually kill off the HIV viruses. If thats the case, what happens to the viruses that are already replicated and floating around in the blood?

Also, I just don't understand why these meds should give lipo side effects on people. They seem to be very specific to certain enzymatic actions and protein synthesis and nothing to do with lipids. For example, Nukes and Non Nukes only deal with reverse transcriptase which is only involved in virus replication, if thats the case, how can they possibly interfere with other natural bodily functions?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline Assurbanipal

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Re: Truvada and Viramune Combo Question
« Reply #12 on: March 26, 2010, 08:03:21 PM »
All sorts of chemicals, bits of viruses, broken cells are routinely swept up and excreted from the body.

The NRTI's in particular are bad copies of the nucleotides that go into building DNA -- so the body may mistake them for what it needs for other DNA/RNA transcription functions. 

Actually, I found the AIDSMEDS 2D write-up a lot easier and more helpful after the 3D version. 

Try it here
http://www.aidsmeds.com/articles/hiv_life_cycle_5014.shtml
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline rmgjunk

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Re: Truvada and Viramune Combo Question
« Reply #13 on: March 26, 2010, 08:33:51 PM »
Also, I just don't understand why these meds should give lipo side effects on people. They seem to be very specific to certain enzymatic actions and protein synthesis and nothing to do with lipids. For example, Nukes and Non Nukes only deal with reverse transcriptase which is only involved in virus replication, if thats the case, how can they possibly interfere with other natural bodily functions?

Not all of them do, and not to the same degree.  You were right to ask if nucleotide/nucleoside analogs interfere with human DNA synthesis, the catch is how much.  These drugs are tolerable because they tend to bind to HIV enzymes hundreds of times more easily than to human enzymes.  They fool HIV's chemical reactions much more than ours, and there's also some variation from person to person.

AZT sometimes causes a condition called Macrocytosis (http://en.wikipedia.org/wiki/Macrocytosis), literally enlarged red blood cells, because it makes cells take longer to build new DNA and they grow bigger before dividing.  (I have that, btw, and it's harmless if you don't have associated anemia).  Some drugs don't interfere with DNA synthesis on the cell's nucleus, but cause some damage to mithocondrial DNA synthesis, and I recall reading somewhere that's the cause of the lipo issues, because it messes with the way your body processes lipids (someone please correct me if I'm wrong).

But don't get scared, really don't :-)  The NRTIs commonly used today, on the dosages used today, have a much smaller impact on cell chemistry.  The drugs combined in Truvada are particularly good at targeting HIV enzymes and sparing the human ones.

[]s
Roger
14-Sep-2009 Tested positive
Last labs: VL <47, CD4 441/29%
Current meds: AZT, 3TC, Nevirapine

Offline egello

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Re: Truvada and Viramune Combo Question
« Reply #14 on: March 26, 2010, 08:53:06 PM »
when you say enzyme do you mean like polymerase that will bind nucleotide to RNA? But i thought humans don't have polymerase that can attach nucleotides to RNA, but only to DNA since we don't use RNA to replicate DNA....  as i said in my other post, if NRTIs are just bad nucelotides, why can't it bind equally to human DNA transcriptase process as they bind to HIV RNA reverse transcriptase process?
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline rmgjunk

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Re: Truvada and Viramune Combo Question
« Reply #15 on: March 26, 2010, 09:25:10 PM »
Actually it's all about DNA synthesis.  HIV comes with an RNA recipe that its reverse transcriptase reads to build DNA from it.  That RNA by itself is useless, it needs to be transcribed to DNA, that in turn gets integrated (by integrase, another viral enzyme) to the cell's nucleus.  There's more to that, but it gets way beyond by biology skills :-).  The wikipedia article on reverse transcriptase states that it "is a DNA polymerase enzyme that transcribes single-stranded RNA into double-stranded DNA".

Although they have similar goals, reverse transcriptase (RT) and human DNA polymerase (DNAp) are very different substances.  That difference is what makes it possible to have a drug that "fools" RT into using it instead of the right nucleotides, and at the same time is mostly ignored by DNAp.  But I can't really explain what molecular affinities are responsible for that difference, I just take for granted that some chemicals will react together while others won't :-)

[]s
Roger
14-Sep-2009 Tested positive
Last labs: VL <47, CD4 441/29%
Current meds: AZT, 3TC, Nevirapine

Offline egello

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Re: Truvada and Viramune Combo Question
« Reply #16 on: March 26, 2010, 09:39:06 PM »
thanks for your explanation
Reyataz / Norvir / Truvada/ Androgel 5 g / 2 days
1/29/07 14 T, 300 k V, 1.8 %
2/22/07 197 T, 247 V, 6.8 %
3/27/07 164 T, <50 V, 5.4 %
5/28/07 177 T, <50 V, 8.2 %
7/28/07 214 T, <50 V, 9.6 %
10/3/07 380 T, <50 V, 10 % no more Mepron, Famvir

Offline rmgjunk

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Re: Truvada and Viramune Combo Question
« Reply #17 on: March 26, 2010, 09:55:56 PM »
I'm glad I've helped :-)  And good luck on your new combo, whatever decision you make.

[]s
Roger
14-Sep-2009 Tested positive
Last labs: VL <47, CD4 441/29%
Current meds: AZT, 3TC, Nevirapine

 


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