Is first line out of the question?
Dec 30, 2009
Hi I am treatment naive and have some NRTI resistance. I'm pretty sure it was a genotype resistance test as I recall seeing what looked like a list of mutations on the paper. It was reported as 'low level resistance' to Stavudine and Zidovudine and 'potential low level resistance' to all other NRTIs apart from 3tc and ftc.
I do not know the mutations at this time.
Couple of questions. Firstly, if certain mutations cause resistance to some drugs how can a test result report 'potential' resistance. Surely it just does or doesn't?
and if it was a phenotype test then i still don't get the 'potential' resistance result as I would have thought the drugs would have either worked or been less effective resulting in no resistance or a certain level of some resistance.
Second of all, I've read that 3tc and ftc cannot be used together in a double NRTI regime. Is a single NRTI + an NNRTI +a boosted PI a likely alternative? And can a regime like this with one NRTI work?
Thanks very much
Response from Dr. McGowan
Thanks for these questions. Resistance testing can be complicated even for doctors.
The issue of "potential" resistance is due to the fact that it may take 2 or 3 mutations in the virus to render it "fully" resistant to the effects of a medicine. So, for example, if you need mutations X, Y and Z to get high level resistance to a medicine but the virus only has X and Y..the medicine may have some activity but it is "damaged goods". It could not be relied on to be fully active.
Sometimes, especially if the test was done when a person is not taking meds (like your case pre-treatment) there may be more mutations that are present but not detected because they are at a low level. Taking the medicine would force the virus to "show its' hand" and reveal all its mutations so that it can survive. So finding all these NRTI mutations in your virus pre-treatment means that your regimen of medications is going to have to include drugs from at least 2 other classes of treatment to be effective.
The phenotype is a different way of detecting resistance. Instead of working out the genetic code of the virus and finding all its mutations (like in a genotype test), the phenotype grows the virus in the presence of the medicine to see if it is inhibited. In your case, the phenotype may be less helpful than the genotype test to find resistance because having 1 or 2 mutations may slow the virus but not enough to show up on the phenotype. It's like a car with a bad tire..it may run OK for a while but that tire is weak and it only needs one deep pothole and you've got a flat. If you knew the tire was damaged you would buy a new one and not wait for it to burst. The genotype is like that...it shows the damage is there even if it is only "potential" at this point.
Your first treatment should include at least 3 Fully Active medicines. So an active NRTI + boosted PI + NNRTI could be a good combo since it would have 3 active drugs including a boosted PI which is quite potent.
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