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Author Topic: Major and minor resistance  (Read 2246 times)

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Offline frenchpat

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Major and minor resistance
« on: November 02, 2006, 07:41:33 AM »
Hi everyone,

I've just received the results of my genotypic resistance test. For each drug it states a major and a minor resistance.
For example:

Lexiva:  Major:   none
               Minor:   L10I-I62V

Reyataz:  Major:  none
                  Minor:  L10I

and the list goes on.

the only major resistance I seem to have are for 3TC/FTC (M184V) and for D4T (T215F/I/S/T), this last also being a Major one for AZT.

I had never heard of minor resistance before and despite reading the lessons here.

Anyone care to enlighten me?

thanks a lot,

Pat
People have the power - Patti Smith

Offline MSPspud

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Re: Major and minor resistance
« Reply #1 on: November 02, 2006, 12:42:50 PM »
Well my take on it is that Major resistance indicates you're fully resistant and will receive little to no benefit from taking the drug. 

Minor resistance indicates that there is still significant viral response to the drug; however there is a reduction into how potent it really is.  Such as; a 20% reduction in the drug's effectiveness for each minor mutation (don't quote that figure).  B/c of this, a protease inhibitor may need to be boosted by ritonavir to be fully effective where-as it would not w/o the mutation(s). 

As to the specific % drops in effectiveness for a major or minor mutation, I'm not the expert.

Offline newt

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Re: Major and minor resistance
« Reply #2 on: November 05, 2006, 03:41:42 AM »
Resistance tests classify mutations as major or minor based on whether they affect particular drugs working, using info from research and databases of other people's test results.

Pat, in your case the PI mutations are neither here nor there.  The nuke mutations - M184V and T215F - will affect the working of some drugs.

M184V - No surprise there, because you've been on 3TC with an unsuppressed viral load for a while.  M184V causes high-level resistance to 3TC (and FTC) but this strain of HIV is more susceptible to Viread, so a typical nuke pair used in this scenario is Viread + 3TC or FTC (eg Truvada).

T215F - On its own this gives intermediate resistance to AZT, d4T and Ziagen (and to a lesser extent, ddI, and Viread). Combined with M184V, this probably means AZT, Ziagen (and maybe ddI) will be ineffective. You will need to look at the individual drug effectiveness cut-off values on your resistance test to find out how much the strength of each of these meds has been reduced.

- matt
« Last Edit: November 05, 2006, 08:40:35 AM by newt »
"The object is to be a well patient, not a good patient"

Offline gerry

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Re: Major and minor resistance
« Reply #3 on: November 05, 2006, 12:35:33 PM »
Pat:

You should be okay with using a boosted PI (which you have not used in the past) with those minor mutations.  The question is what NRTIs to combine it with, if any, considering that you were on dual, nonsuppressive nuke therapy (Epivir/Zerit) for 18 months.  Did it show other NRTI mutations (even if they are not "major")?  The reason I ask this is the 215 resistance pathway usually gives rise to cross-resistance to other NRTIs.  It is also possible, if it was detected by itself, that the other so called "TAMs" (resistance mutations that occur sequentially to those on nonsuppressive regimens containing AZT or Zerit) may have been present but not detected by the test.  Did your doc order a phenotype test as well?  This will be important to tell if other NNRTIs you haven't used could be usable in combination to a boosted PI.  If not, you may have to go to an unconventional combo, such as one that contains a boosted PI and NNRTI, or double-boosted PI.

Gerry

Offline frenchpat

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Re: Major and minor resistance
« Reply #4 on: November 07, 2006, 10:51:08 AM »
Thank you guys,

wel, your thorough answers lead me to open pandora's box in the full, so here is the complete list:

Abacavir (Ziagen): Major (none) Minor (M41L/M - M184V - T215 F/I/S/T)

Didanosine (Videx): Major (none) Minor (M41L/M - T215 F/I/S/T)

Lamivudine/Emtricitabine (Epivir/Emtriva): Major (M184) Minor (none)

Stavudine (Zerit): Major (T215 F/I/S/T) Minor (M41L/M - K70R/K)

Tenofovir (Viread): Major (none) Minor (M41L/M - T215 F/I/S/T)

Zidovudine (AZT): Major (T215 F/I/S/T) Minor (M41L/M - K70R/K)

Efavirenz (Sustiva) : Major (none) Minor (none)

Nevirapine (Viramune) : Major (none) Minor (none)

Etravirine (TMC 125) : Major (none) Minor (none)



fosAmprenavir (Lexiva) : Major (none) Minor (L10I-I62V)

Atasanavir (Reyataz) : Major (none) Minor (L10I)

Darunavir (Prezista) : Major (none) Minor (none)

Indinavir (Crixivan) : Major (none) Minor (V77I)

Lopinavir (Kaletra) : Major (none) Minor (L10I-L63P)

Nelfinavir (Viracept) : Major (none) Minor (L10I-V77I)

Saquinavir (Invirase): Major (none) Minor (L10I-I62V)

Tipranavir (Aptivus): Major (none) Minor (none)


Apparentlly a vagrant E35D was found too but according to the lab its effects are uncertain or havent been described yet...

Interpretation as per the ANRS (National Agency for AIDS Research) AC11 Resistance group is as follows:

Resistance to Lamivudine, Stavudine, Emtricitabine and Zidovudine.


In searching for more info I found these sites that can be of interest to others:

http://www.hivfrenchresistance.org/tab2006.html

http://pugliese.club.fr/index.htm

thanks for your patience and help  :-*

Pat













People have the power - Patti Smith

Offline frenchpat

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  • Love your friends, don't eat them.
Re: Major and minor resistance
« Reply #5 on: November 11, 2006, 06:01:48 AM »
Gerry and Matt (Newt), and anyone else who feels like giving me some advice,

what combo do you think would work best?

before getting the results of the resistance test my doc was thinking Lexiva, Norvir and Truvada. After reading my test he's advising to go back to what he'd proposed in july: Kaletra, Ziagen, Viread.

I am not sure what to make of this after reading your answers (Ziagen or not? have no cutoff values on the test).

when you have the time,

thanks

Pat

People have the power - Patti Smith

Offline newt

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  • the one and original newt
Re: Major and minor resistance
« Reply #6 on: November 11, 2006, 06:39:51 AM »
Ziagen, no, prob. not.  The cut-off for Ziagen is a 3-fold change in effectiveness, your resistance pattern suggests Ziagen will be 6+ times less effective (but see below). 3TC and FTC super resistant (but see below). Viread (tenofovir) still nearly bang on 100% effectiveness.

Therefore, my starting point would be:

EITHER an NNRTI (Sustiva, Viramune) OR a boosted PI (Lexiva or Reyataz + Norvir booster or Kaletra)

PLUS Viread + FTC or 3TC. 

While you have resistance to 3TC and FTC, the mutation in question makes this type of HIV more susceptible to Viread. You could use Ziagen for the same reason, but Viread + FTC comes in a handy one tablet co-formulation (so less pills).

Where did I check? Stanford HIV Drug Resistance Database for one. This was just really to confirm my initial thinking.

If you wanna go a different route, you's could look at an NNRTI + boosted PI + 3TC option. But seems unnecessarily complex as a starting point.

- matt

Now playing: Antonio Vivaldi, Concerto for 2 Trumpets and Strings (RV. 537)
"The object is to be a well patient, not a good patient"

Offline frenchpat

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  • Love your friends, don't eat them.
Re: Major and minor resistance
« Reply #7 on: November 11, 2006, 08:16:56 AM »
Matt,

thank you so much for the comment.
The link is very helpful too.

I shall discuss this with my doctor again...

Pat
People have the power - Patti Smith

 


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