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so sorry didn't quite understand
Dec 31, 2009

Hello it's me again about NRTI resistance. Thanks for answering and sorry for the panicked string of same questions! and sorry for asking another so soon but i want to be quite sure i understand.

I understand that one or two mutations might make a drug resistant to a low level (but a higher combination or specific mutation might be needed to confer high resistance) and i have confirmed low level resistance to stavudine and zidovudine. I presume this means that these drugs might have some activity and could, for example, play a role in future salvage therapy.

However I don't get how that explains having 'potential low level resistance' to other NRTIs (except 3tc/ftc) surely if there is a combination of mutations that cause resistance then that resistance (at some level) would be confirmed (as in the case of stavudine and zidovudine) and if these mutations or combinations of mutations do not exist then susceptibility is confirmed (as the results showed with 3tc/ftc and other classes)

By your reply it seemed to imply that the 'potential low level resistance' should be taken to be definite low level resistance (as with zidovudine and stavudine) is this how i should look at things?

Thanks so much for your help I reckon I'll start treatment in 2010 and so want to know as much as possible any my next checkup isn't for 7 weeks.

Response from Dr. McGowan

I think the word "potential" is what is confusing.

When there is a series of mutations on the genotype it indicates that the virus growth may be effected by these mutations. Some mutations have a stronger effect on the growth of the virus than others...so it isn't just the number of mutations that need to add up, it is also the specific ones. We call these primary and secondary mutations. You may only need 1 or 2 primary mutations to get a high level resistance to a medication, but you might also get there by having 3 or 4 secondary mutations.

To make things a little more complex these mutations can effect more than one medicine. So mutations selected while a person was taking zidovudine may also effect the other NRTIs such as stavudine, abacavir, tenofovir and even lamivudine. This is called "cross resistance". If your virus has a bunch of these primary zidovudine mutations it may have "potential resistance" to another NRTI, that is, it is possibly resistant. These zidovudine mutations may also be primary or secondary mutations to another NRTI. The test is pretty good at predicting the effect of these mutations but it is not exact, especially if there are a number of mutations that could interact and effect the growth of the virus. That is why they can say there is a potential for resistance. The mutations are there but the exact effect on the growth of the virus for one or more of the medicines may not be exactly predictable if there are only secondary mutations, for example.

Hope this helps and doesn't confuse you more.

Joe



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