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Author Topic: Deciding On A Regimen--Questions  (Read 5850 times)

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Offline tednlou2

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Deciding On A Regimen--Questions
« on: October 08, 2013, 12:46:59 am »
In 2009, I picked out the regimen Truvada, Reyataz, and Norvir, as my regimen for when I would start meds.  As most know, I never started, as I had pretty decent labs.  After a couple off labs over the summer, I decided it was time to discuss med options again, in case I would need to make a decision in the near future.

We went over Complera and Stribild, which were not options back in 2009.  I could tell the pharmacist counselor was biased toward these one pill a day regimens over the one I had chosen previously.  One pill a day did sound like the better option.  So, I've been trying to read up on these different regimens.  I asked Dr. Young at The Body his thoughts on these regimens.  He seems to be very knowledgable.  I think he is the director at a hospital in Colorado.  He said due to my K103n mutation, that I got from the hospital having me only on Sustiva and then stopped on discharge in 2008, the resistance would knock out Complera as an option for me.  He said because I had resistance to most NNRTI's, the Rilpivirine would be an issue for me, as it is in the NNRTI class.  He also said although not as bad as Sustiva, it also can cause issues for those with depression and anxiety. 

So, I was thinking Complera is not an option.  And, I was miffed that my HIV clinic would tell me it was an option.  However, I was just reading that Rilpivirine is different from the older NNRTI meds.  If I read this correctly, it was saying that it has a way to get around the NNRTI resistance that would have made it not an option in the past.  I will post that article below. 

I'm curious what the med educated folks here know about this.  Is Dr. Young incorrect and my HIV pharmacist counselor correct?  I'm also curious whether the one pill a day regimens would be a no-brainer over the Truvada, Reyataz, and Norvir.  It would seem that way, to me.  But, I have not done as much research on meds as I should have over the last few years. 

From the article I read, " Rilpivirine and the recently approved etravirine, made by Tibotec Pharmaceuticals, were designed specifically to meet the drug-resistance challenges posed by a rapidly evolving viral target.

NNRTIs work by binding to amino acids within a "pocket" contained on the reverse transcriptase enzyme, interfering with the enzyme's function and forestalling the first phase of HIV replication within the host cell. Resistance to NNRTIs occurs when mutations inside the pocket prevent the drugs from binding there, or when a single mutation (known as K103N) alters the opening of the pocket sufficiently to block NNRTIs from entering.

New NNRTIs were designed to get around these resistance mechanisms through "conformational flexibility": both etravirine and rilpivirine are able to alter their shape and position (through processes scientifically termed "wiggling" and "jiggling") in order to enter and bind to the pocket on reverse transcriptase in HIV that carries first generation NNRTI resistance mutations. The benefits of this flexibility, as well as the new drugs' improved side effect profiles, are evident in promising results from advanced clinical trials." 

http://www.thebody.com/content/art46396.html


Offline newt

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Re: Deciding On A Regimen--Questions
« Reply #1 on: October 08, 2013, 05:58:35 am »
K103N alone will not rule out rilpivirine, depends on any other mutations. The CNS side effects seem about half those on efavirenz.  A 3 pill Truvada +  boosted PI once a day is not that onerous really (I prefer Prezista to Reyataz with Truvada). Stribild seems a goodie, but it's new, so the shine will come off a bit as side effects get better characterised.

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

Offline tednlou2

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Re: Deciding On A Regimen--Questions
« Reply #2 on: October 08, 2013, 03:15:50 pm »
K103N alone will not rule out rilpivirine, depends on any other mutations. The CNS side effects seem about half those on efavirenz.  A 3 pill Truvada +  boosted PI once a day is not that onerous really (I prefer Prezista to Reyataz with Truvada). Stribild seems a goodie, but it's new, so the shine will come off a bit as side effects get better characterised.

-matt


Thanks, Matt.  Your last part is something I was considering, as well.  Having said that, have there been any newer meds (post 1996) that were shown to cause serious issues?  I mean, none were taken off the market or anything like that?  Well, I read Truvada didn't show all the renal issues in the trials, that were seen in the real world, no?  But, didn't they just reformulate it?  The one thing I noticed about Complera and Stribild (think both) was serious liver issues possible.  But, don't all say that?  The same with their warning on development of fatty liver?  I have mild fatty liver now.  Many PI's carried fatty liver as possibilities, I think.  And, I know it is believed that metabolic changes, from the virus, could be the big factor on that.  And, so many western folks have fatty liver anyway. 

Offline buginme2

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Re: Deciding On A Regimen--Questions
« Reply #3 on: October 08, 2013, 11:17:29 pm »


According to the Stanford university database the K103N resistance is still susceptible to rilpivrine.  It is resistant to Sustiva and Nevirapine.


Non-Nucleoside RTI
efavirenz (EFV)   High-level resistance
etravirine (ETR)   Susceptible
nevirapine (NVP)   High-level resistance
rilpivirine (RPV)   Susceptible

They have a database you can enter your specific resistance and it will tell you what meds you can and can't take.

http://sierra2.stanford.edu/sierra/servlet/JSierra?action=mutationsInput

As far as which med is better and which is worse..really. I think its six of one half dozen of the other. 


Don't be fancy, just get dancey

Offline tednlou2

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Re: Deciding On A Regimen--Questions
« Reply #4 on: November 13, 2013, 08:54:51 pm »

According to the Stanford university database the K103N resistance is still susceptible to rilpivrine.  It is resistant to Sustiva and Nevirapine.


Non-Nucleoside RTI
efavirenz (EFV)   High-level resistance
etravirine (ETR)   Susceptible
nevirapine (NVP)   High-level resistance
rilpivirine (RPV)   Susceptible

They have a database you can enter your specific resistance and it will tell you what meds you can and can't take.

http://sierra2.stanford.edu/sierra/servlet/JSierra?action=mutationsInput

As far as which med is better and which is worse..really. I think its six of one half dozen of the other.

Thanks for looking that up and giving me the link.  As someone who should know more about meds and resistance, I don't.  So, this confused me.  I see where it says there is susceptibility, but then it says this:


RT Comments
NNRTI
K103N causes high-level resistance to NVP (~50-fold reduced susceptibility) and EFV (~20-fold reduced susceptibility). it has no effect on ETR or RPV susceptibility.

What does it mean by saying it has susceptibility but then saying the mutation has no effect on rilpilvirine??  What other mutations should I be checking, if I go the Complera route over Stribild?  I really don't trust the pharm folks at my HIV clinic.  So, I will request copy of my resistance test.  I may have a copy already.  When I find that, then I just enter those into that database? 

Offline tednlou2

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Re: Deciding On A Regimen--Questions
« Reply #5 on: November 16, 2013, 12:51:07 am »

According to the Stanford university database the K103N resistance is still susceptible to rilpivrine.  It is resistant to Sustiva and Nevirapine.


Non-Nucleoside RTI
efavirenz (EFV)   High-level resistance
etravirine (ETR)   Susceptible
nevirapine (NVP)   High-level resistance
rilpivirine (RPV)   Susceptible

They have a database you can enter your specific resistance and it will tell you what meds you can and can't take.

http://sierra2.stanford.edu/sierra/servlet/JSierra?action=mutationsInput

As far as which med is better and which is worse..really. I think its six of one half dozen of the other.

I just realized I misinterpreted what this said.  I was reading it as K103n would knock out rilpilvirine.  It was late and I was reading it as rilpilvirine susceptible to K103n.  When I read it now, I realized I made an error and this means the drug works on this mutation.  I have that correct now, right?  Lol. 


Offline tednlou2

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Re: Deciding On A Regimen--Questions
« Reply #6 on: December 18, 2013, 01:04:13 am »
Well, I guess I'm leaning toward Stribild.  After further questioning, it does appear Complera would work, even with my K103n mutation.  But, I've read if you become resistant to it, it would or could knock out other options.  Does anyone know more about this?  Does this mean knock out drugs like the Sustiva in Atripla, which I'm already resistant?  What drugs/regimens are people talking about, when they discuss becoming resistant to Complera?  If it means knocking out NNRTI's that I'm already resistant, then this wouldn't be a factor for me. 

Is there a good site to look at the pros and cons of Complera and Stribild?  Because as of now, it feels like I would have to flip a coin.

Offline buginme2

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Re: Deciding On A Regimen--Questions
« Reply #7 on: December 18, 2013, 07:27:34 pm »
I think if you become resistant to the rilpivrine in Complera you would also be resistant to Etavirine. 

I think that's what they try to avoid because Etavirine is used in people who have become resistant to other meds.  I think its one of those that was developed for people with resistance so it's not given to treatment naive patients, just treatment experienced. 

So...if they are concerned that your already resistant to half of the NNRTI's (Sustiva and nevirapine) they may not want to put you in a situation that would knock out the other two (rilpivrine and etavirine), especially since Etavirine is used for the more experienced patient.

With that being said, Stribild sounds reasonable.  Do you have concerns about Stribild?
Don't be fancy, just get dancey

Offline tednlou2

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Re: Deciding On A Regimen--Questions
« Reply #8 on: December 22, 2013, 03:23:05 am »
I think if you become resistant to the rilpivrine in Complera you would also be resistant to Etavirine. 

I think that's what they try to avoid because Etavirine is used in people who have become resistant to other meds.  I think its one of those that was developed for people with resistance so it's not given to treatment naive patients, just treatment experienced. 

So...if they are concerned that your already resistant to half of the NNRTI's (Sustiva and nevirapine) they may not want to put you in a situation that would knock out the other two (rilpivrine and etavirine), especially since Etavirine is used for the more experienced patient.

With that being said, Stribild sounds reasonable.  Do you have concerns about Stribild?

I still don't know enough about these newer regimens to have concerns.  From what I've read, Stribild is very effective with low side-effect profile, no?  If I had to make a decision right now, I would choose Stribild. 

 


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