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Done it all, what now?
Mar 22, 2001

Dear Doc:

I'm one of those guys who literally came back from the brink of death a few years ago. Got into one of the first protease clinical trials and it really saved my life. Unfortunately, now I'm also one of those guys with a huge belly and no cheeks - on my face or my butt - yes I've got lypodistrophy. I'm doing o.k. I got lucky. My T-cells have stayed around 200 even though my viral load hasn't been under 5,000 for about a year. I decided, with my doctors permission, to take a treatment holiday three months ago. I've just been on meds of one sort or another for over nine years. I couldn't stand it anymore, especially with what it was doing to my body. Well, now my viral load is over 100,000 and I've got to go back - ugh. My insurance won't pay for the resistance tests - I've got a little money saved so I could pay for them if I had to. Because I've been on just about everything, I'd be willing to pay for the resistance tests if you think they would help me choose a combination that will most likely work for me. But I don't want to waste the money if it won't help. It may just be a crap shoot anyway. If I do pay for them, is one better than another? How many times would I have to take them? Thanks a lot for your answer.

Response from Dr. Little

Your question falls into two parts: should you have a resistance test? And if so, which one? I am a strong believer in the utility of a good clinical history which I am sure that your physician has taken. That is, a careful review of which antiretrovirals (ARV) you have taken, for how long, and the reasons for discontinuation (fialure, intolerance, etc.). With this information, it is often possible to make very educated guesses about the best treatment combination for somone with multiple treatment options, with the understanding that many of the "best" choices are not possible if the setting of significant past toxicities or intolerances. Having said this, in the setting of more restricted treatment options (and likely significant drug resistance due to extensive prior ARV use), you don't want to choose anything short of the best treatment option. If you were still taking your therapy (ie. had not interrupted your therapy), I would strongy urge you to get a drug resistance test. The difficulty of your current situation is that in the absence of ongoing ARV therapy, some of the existing drug resistance mutations may have reverted - changed back - to drug sensitive. This occurs because of an outgrowth of pre-existing drug sensitive virus which grows well in the absence of ARV therapy and may in fact replace the drug resistant variant, such that drug resistance testing after a treatment interruption (especially greater than 8-12 weeks) may not detect the presence of a drug resistant variant, EVEN THOUGH IT IS STILL PRESENT. However, despite all of this information by way of background, to answer your question, YES, I do believe that drug resistance testing in your situation might well be useful. This is not a guarantee however, given the constraints I have tried to outline. The bottom line, is that as treatment options become more limited, the penalty for making suboptimal treatment "guesses" based upon clinical history are greater, and the added information that drug resistance testing offers may be significant.

The choice of whether to request a genotype or phenotype I believe should be based upon which one your provider is more comfortable interpreting. Phenotype testing is often easier to interpret, but may give less information about more remote treatment experience. In contrast, genotype testing often provides more information, but is MUCH more difficult to interpret, even among experts. So the choice of test should be discussed with your docotor and hopefully whichever test is selected will provide you with the information that you and your provider need to make the best treatment choices for your future.

How resistance is Norvir?

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