Managing HIV/AIDS Therapy in Treatment-Experienced Patients What are some switching strategies for lipodystrophy?
	Enlarged Version of Graphics Below	Dr. Bellos (OC): ...I think we need to be clear in terms of what we are talking about, when we talk about lipodystrophy. My common response to that is that it's sort of like the Supreme Court ruling about pornography. I can't give you a definition completely, but I know it when I see it... Dr. Bellos (VO): ...I think that's one thing that we have to look at, in that there is some body habitus changing that is associated with lipodystrophy-the sunken cheeks, the development of a buffalo hump, the abdominal-what used to be called the "protease paunch," the increase in the abdominal girth; the new term that was coined, which I thought was relatively interesting, was called "venomegaly," where you have significant showing of the veins in people's arms and legs, the loss of limb fat, and the development of trunk fat.   See Slide Dr. Bellos (OC) : ...I think one of the difficult things at this juncture for clinicians has been trying to truly define lipodystrophy, because not only does it result in the anthropomorphic changes that we see, but also in the metabolic changes that we see in patients, in terms of increased lipids, in terms of increased sugars. Now, in terms of responding to that, I think what one has to do-we never know who's going to develop these complications. Patients, for example, who have been on d4T for years, and are doing well virologically, immunologically, and have no evidence of lipodystrophic changes; patients who will begin on d4T, and in six months have developed significant lipodystrophic changes-I think one of the issues is trying to decide, A: Which patients are going to do that? B: Then, one needs to avoid those drugs in those patients. Unfortunately, we don't have the science to be able to predict those patients, but we now do have some knowledge about some of the drugs. For example, the thymidine analogues that can potentially result in some of these changes, so I think that from the early perspective, unless there is a real necessity or a real need to use one of the thymidine analogues, it may be better-especially since we're talking about lifelong therapy-to potentially avoid the thymidine analogues up front, and use drugs in combination; for example, like abacavir/3TC, that are thymidine-sparing, where you can actually not have some of these changes. Initially, these changes were all attributed to the protease inhibitors, and one of the things about HIV infection, and the management of patients is that in my mind, it is very similar to oncology. It's like every day, there's something new, or a new way to approach a problem, which is one of the reasons I find it particularly intriguing, and I think over the years, we have learned that it's not just the protease inhibitors that result in these problems. I mean, some of the nucleosides have been implicated now. Some of the protease inhibitors have been implicated, and even with some of the new classes of drugs, I think we are going to see some toxicities with some of the entry inhibitors, and some of the fusion inhibitors that have to be defined, simply because we don't have enough experience. Dr. Kwakwa (OC): ...when I talk about lipodystrophy, I talk more about the body habitus changes, and also about the metabolic changes, but the body habitus changes are also of great concern to the patients. They may affect adherence, and they are very difficult to treat, so I tend to switch for that purpose earlier in the development of that syndrome rather than later, of course if there's the option to do so. Dr. Wohlfeiler (OC): There are at least two really good studies out there. Dr. Wohlfeiler (VO): One called the TARHEEL study and one called MITOX, which looked at patients who developed fat wasting in the face and in the extremities. One study looked at patients who were specifically on Zerit (d4T) and then switched them to either an AZT or abacavir based regimen. The other study looked at patients who were on thymidine analogs, which could be either AZT or d4T who had lipoatrophy. And then switched them to specifically abacavir containing regimens.   See Slide Dr. Wohlfeiler (OC): And in both of those studies they showed that switching patients led to very slow reversal but reversal of the fat loss and that patients actually started to reaccumulate subcutaneous fat. So those are the kinds of things that really guide my decision to switch because there's evidence out there now in more than one study to indicate that if you switch you could really make the problem better. Dr. Bellos (OC): If the patient had been on a thymidine analogue, that I think one of the things that we would consider doing would be to switch that patient from a nucleoside perspective to a non-thymidine analogue nucleoside. Dr. Bellos (VO): If you look at the toxicities with respect to the mitochondria from the thymidine analogues, the one that has the most effect on mitochondria is d4T, followed by AZT, followed by 3TC/abacavir, and on down the line.   See Slide Dr. Bellos (OC): Tenofovir, being a nucleotide analogue, theoretically should not have potential mitochondrial toxicities, but the issue with tenofovir is that there could be potential for nephrotoxicity in patients, especially in patients with comorbidities such as hypertension and hyperglycemia that pose risks to the kidney just from their own innate presence, and I think that one would need be judicious in the use of tenofovir in those patients and to monitor them closely, and with any sign of renal toxicity-for example, proteinuria or a slight elevation of creatinine-one would need to strongly consider altering a tenofovir-based regimen. Dr. Bellos (VO): The other side of that coin is that one could use a nucleoside-based regimen that contained Epzicom, which contains abacavir/3TC, which has no thymidine analogue component, and also is relatively clean from the perspective of renal toxicity. However, again in that setting, as I mentioned previously, we like to think of these drugs as totally clean, but they're not, and one must weigh the risks of the potential for a hypersensitivity reaction,   See Slide Dr. Bellos (OC): I want to reiterate that in my patient population, in the thousands of prescriptions that I've written for abacavir, I have seen probably five or six hypersensitivity reactions. Dr. Kwakwa (OC): Well, the particular body habitus changes the patients tend to notice most and that they feel particularly self-conscious about are the lipoatrophic features, and there, I would tend to change the nucleosides. There, I would change to an abacavir, or a tenofovir, depending on the particular patient.
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