Managing HIV/AIDS Therapy in Treatment-Experienced Patients What are the reasons behind treatment failure?
	Enlarged Version of Graphics Below	Dr. Wohlfeiler (OC): Probably the number one reason is lack of adherence. And that could be from the outset a patient who has never been appropriately adhering. We see patients get fatigued with their regimens. I have seen patients who have been very adherent to the regimen for years who start to develop treatment fatigue or pill fatigue and start to miss doses and then will develop resistance. Dr. Bellos (OC): Nonadherence is the biggest reason patients will fail treatment. The other reason that we see even in an adherent patient is the fact that they may develop resistance. Dr. Wohlfeiler (OC): Obviously if you don't pick the right regimen at the outset, if you've got patients who have preexisting resistant mutations and you don't detect those or don't follow up on that appropriately monitoring that, you can have a failure for that kind of reason as well. Dr. Bellos (OC): One of the other issues with respect to failure that we are seeing in patients, especially those who have been on therapy long-term and have been adherent with their therapy, are toxicity reasons for failure. These may be patients who are immunologically competent and have had a robust virologic response, and are maintaining that virologic response, but are beginning to have toxicities associated with their nucleoside backbone-for example, they're developing hyperlipidemia, they're developing mitochondrial toxicities, they're developing lipoatrophy, lipodystrophy, or they are developing hyperglycemia as a result of their therapies. Those are patients for whom we would probably need to look at altering their nucleoside backbone, or even have the potential of switching them off of the nucleoside backbone, and using a dual boosted PI regimen. There's very little data, but there are several trials underway looking at those in terms of therapeutic alternatives for patients who have experienced severe toxicities.   See Slide Dr. Bellos (OC): I can tell you in my own experience-my own personal experience-it's something that I have done in patients who come in significantly lipodystrophic, or with significant issues with mitochondrial toxicity, and simply refuse to take nucleosides any longer. Then in those patients, we have actually been able to have a good virologic response and a robust T-cell response when we place them on a dual boosted PI regimen. Dr. Kwakwa (OC): Nonadherence is an important one, and drug-to-drug interactions also, the kinds of interactions that may give less of an exposure to a particular drug for the patient. For example, the use of-and this is just an example-the use of proton pump inhibitors in a patient who is on Reyataz, for example, particularly if they are also on tenofovir. Another increasingly important reason is pre-existing mutations. Sometimes, we forget that "naïve patient" does not always mean naïve virus. Announcer (VO): The prevalence and class-type resistance at baseline was measured in 491 treatment-naïve subjects who were entering the CPCRA 058 study. Close to 11% of all subjects had some form of resistance to any drug class at baseline. For specific classes, the rate was nearly 8% for nucleosides, 3% for non-nucleosides, and less than 1% for protease inhibitors.   See Slide
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