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Managing HIV/AIDS Therapy in Treatment-Experienced Patients
What if there is failure with no resistance identified?
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Dr. Kwakwa (OC): In the individual with no resistance identified but with a rising viral load, or an inadequate virologic response, I would look very carefully at the individual's adherence to the medication regimen. Now, in the individual who is on a regimen with very high levels of resistance-examples being boosted fosamprenavir-based regimens, or a boosted lopinavir-based regimen, the phenomenon of actually failing virologically with no resistance or very little nucleoside resistance has been reported, even in patients who may be adherent to the medication, and that is also a consideration.
Dr. Wohlfeiler (OC): The first thing that you think of if somebody's failing and they show sensitivity to every drug in their regimen is an adherence issue. Now I'm convinced that there are some patients who truly are fully adherent to their regimen who are having virologic failure and come back with resistance tests looking like they aren't taking the meds.
And I think that that is a certain subset of patients who maybe absorb or metabolize these drugs differently and have much more difficulty achieving therapeutic levels of their medications. I think that's relatively rare. In those patients the way that you could try to approach it would be if you could access a TDM or therapeutic drug monitoring and really see what their levels are, though there are certainly concerns about accuracy of TDM and so forth. It's not really well standardized yet.
Dr. Kwakwa (OC): When it comes to deciding whether to switch or to intensify, I think it's clear that if there's resistance to more than one agent in a regimen, switching then becomes the preferable alternative.
Dr. Kwakwa (VO): If there is a very low viral load, low enough that resistance can't be determined, for example, then intensifying, of course, becomes an option, and that depends on, sort of, what medications are in the regimen, and what the likely pattern of resistance, if it exists, would be. With a regimen containing 3TC, and very, very low level viremia, below the level at which resistance can be determined, for example, intensification perhaps with a medication that in the presence of lamivudine resistance-which the virus would be hypersusceptible to, would be an option there.
If I started with the boosted protease recommended in the guidelines, I would be more inclined to intensify. If I started with a non-nucleoside, where with a low-level viremia, I might have not only an M184, but also, a K103N with non-nucleoside resistance, I would tend more to switch in that instance, yes.
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