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Many mutations listed on my Genome/Phemone Test
Sep 11, 2009

Hello Dr. Sherer,

I just received my Genome/Phenome Test back and found that I have the K103N mutation so my Dr. took me off Atripla and put me on Truvada and Intelence.

At the end of the test, it also gave a complete listing of Mutations Detected in the test, which are G15G/R, K20R, V21I, V35M, T39A, G45G/E, Q102K, K103N, K122E, I142T, A158S, C162S, D177D/N, G196D/E, R211K, T215L, P247P/S, V254V/I, R277K, R284R/K, T286A, E291D, V293I, E297K, L10I, R57K, I64V,T74S, V75V/A, V77I, I85V, I93L.

Do many mutations mean a greater risk for potential of drug resistance?

Response from Dr. Sherer

Of the 32 mutations that you list, only 8 - 2 NRTI mutations and 6 PI mutations - are known to be (or, in two cases, may be) associated with reduced sensitivity to drugs in those classes. The remainder of the mutations are 'polymorphisms' that occur naturally due to the highly error prone replication of HIV. There is no evidence that an individual is more prone to subsequent drug resistance if a high number of polymorphisms are observed.

Your resistance test is interesting in having a relatively high number of PI mutations, 3 of which are specifically linked to atazanavir. You did not mention the reason for the test, or any previous regimens that you have taken, but it would be a reasonable to guess that your previous regimen contained atazanavir. I should note, though, that cross-resistance among PIs is quite high, and there is considerable overlap; for example, the V77I mutation is less commonly seen with ATV failures, and more often seen with indinavir, saquinavir, or nelfinavir failures. Hence it is more reasonable to guess that you were previously on a boosted PI. It is also possible that you acquired the virus from someone who failed a boosted PI, though the transmission of such organisms has been a relatively infrequent occurence.

I should also add that your doctor is on solid footing in the switch to etravirine, which is the new second generation NNRTI. Etravirine is relatively unaffected by the presence of the K103N mutation, whereas both efavirenz and nevirapine are fully resistant in its presence.

If you did previously experience a virologic failure with a boosted PI, it is also possible that your apparent full susceptibility to tenofovir and emtricitabine - based on the genotype results - is misleading. I advise that you talk with your doctor about this, and for your both to monitor your progress carefully in the next 6-12 months to ensure that your virus has full susceptibility to all drugs in the regimen.

I suggest that you take this question, and this response, to your next visit to discuss with your doctor.


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