Managing HIV/AIDS Therapy in Treatment-Experienced Patients What can be done for a patient with limited prior treatment and single drug resistance?
	Enlarged Version of Graphics Below	Dr. Wohlfeiler (OC): If somebody's got single drug resistance, the thing that you're really going to do is just switch out that particular drug. That's the easiest situation for resistance testing and for making the decision about what to do because again, it becomes very clearcut. Maybe the one exception to that again would be if a patient develops an M184V on either 3TC or FTC because I am a believer in leaving those drugs onboard because though no mutation is desirable, there are certain benefits to that particular mutation. And so in those situations, instead of switching out 3TC or FTC, I would tend to add something else into the regimen and leave those drugs onboard to maintain the M184V. Dr. Kwakwa (OC): In such a patient exhibiting resistance to a single drug, one option is to switch that one drug out, but then again, it depends on what that one drug is, whether to switch that drug out, or whether, again, to add another drug in, into the mix. Dr. Bellos (OC): It would, in that setting, depend on what the patient's current immunologic and virologic status was. If they only had resistance to one agent, and their viral load was below 10,000, and they were remaining immunologically intact, I'm not going to try to do anything with that patient. The classic example is a patient who has the M184V mutation. That's not somebody where I would necessarily change the 3TC out of their regimen, or change their regimen simply because they have that particular mutation. We know that it occurs within two weeks, and there's even now some data to suggest that that may not actually be a bad thing in terms of maintaining that particular resistance mutation, so it's really a very individual call in that setting. Dr. Wohlfeiler (OC): If there's room for PK enhancement, absolutely, resistance really comes down to nothing more than not having sufficient drug to overcome whatever level of resistance that virus has got. So if you're able to overcome low-level resistance by PK boosting, then that certainly makes sense to try it. Dr. Kwakwa (OC): Changing to an entirely new regimen is always an option. It is an option that I would use if there were issues with the other drugs in the regimen besides the resistance to the one drug. Dr. Wohlfeiler (OC): I wouldn't recommend changing unless you really didn't have any other options. I think that a lot of times, especially with early resistance, low-level viremia...and I'll tell the patients...I look at it as 90% or 95% of the regimen is working well. And we've just got a problem with the other 5% or 10% of it. And so to discard an entire regimen for the sake of getting an extra 5% benefit, I would rather not do that if I don't have to. Dr. Bellos (OC): With respect to the patient who has one resistance mutation, or has essentially lost one drug in their therapy-that's not a patient that I would necessarily be particularly excited about changing their regimen right away. Dr. Bellos (VO): I think I would want a little bit more information, to see how they were tolerating their regimen: if they were having toxicities, or if their viral load was continuing to increase, or they were having immunologic dysfunction. If any of those three entities were present, then I would consider altering the regimen, but with just a single mutation, and with a patient who is tolerating their regimen and has maintain immunologic competence, that's not somebody I would necessarily jump on the bandwagon with to change their regimen.   See Slide Dr. Bellos (OC): I have become much more conservative about rapidity of changing regimens, because I think one of the things we have learned with time is that the more frequently we change regimens, the more quickly we use up drugs, and then, we get to the point where we may not necessarily have the drugs that we need to benefit patients. If you look at, for example, the TORO data, which was with T-20, where they actually looked at the number of drugs necessary for patients to benefit from the introduction of a new class of drugs, basically, patients had to have at least two active drugs in their background regimen in order to achieve the maximal benefit for T-20, and that is sort of a lesson that I keep in the back of my mind, because I would like for patients to have at least two active drugs prior to my switching a regimen.
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