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NRTI choice after phenotype
Mar 30, 2006

Preparing salvage regimen based on TMC114 + TMC125 (approved for EIND), plus fuzeon after 16 weeks off with presumed resistance arhived;(long-term MDR/CD4=0, VL>500K); so my specific question is about interpreting VIRCO phenotype for selection of NRTI salvage component (multi-NRTI-resistant from TAM's); phenotype says susceptible to ddC (FC=2.5), reduced response to ddI (FC=2.3), minimal response to TFV (FC=2.4), resistant to ABC (FC=3.3, but note says some response between 3.2 and 7.5): any thoughts about how to interpret this for NRTI selection?

Response from Dr. Sherer

Thank you for this well-informed question. It is still very incomplete, unfortunately. For example, you didn't mention the genotype results, which add important information that would be useful. And while I'm glad to hear that you understand about archived resistance, it would still matter exactly what drugs you have taken in the past, and the response. All this is to say that these complex situations require a lot of data and don't lend themselves well to an internet Q/A service.

Still, I can make some observations for you and your doctor to consider. The phenotypic cutoffs for abacavir are 4.5 for a decreased response and 6.5 for very little response, so I would lean towards including ABC in your next regimen, and give it a better than 50:50 chance of adding antiviral potency to the regimen.

I would include 3TC as well, even if, as is likely, you have the M184V mutation, for two reasons: an antiviral effect of one half log persists, even with the M184V mutation, and, probably more importantly, 3TC significantly impairs viral fitness.

Of course, you should ignore this advice if you have taken ABC in the past and had a suspected or proven ABC hypersensitivity reaction - and that also illustrates how difficult it is to make this recommendations with too little information.

Tenofovir is also complex to interpret without a genotype, so I would prefer to have all of the TAMs and other NRTI mutations listed before making a judgement on this one.

I also would need to know whether you have the Q-151 complex resistance mutation or the 69-S insertion, which can lead to severe decreased susceptibility for all of the current NRTIs.

This may be enough for now, i.e. a regimen of darunavir (TMC 114) + etravirine (TMC 125) + T-20 + ABC + 3TC. (The latter two could also be given as Epzicom, which is co-formulated ABC + 3TC once daily.) Your doctor may well have other suggestions based on other information as well.

Does Mutations mean Resistant?

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