Managing HIV/AIDS Therapy in Treatment-Experienced Patients What switches should be made for Dyslipidemia?
	Enlarged Version of Graphics Below	Dr. Bellos (OC): The first thing that I try to do with those patients when I see them with respect to their dyslipidemias is I want to essentially try to control those dyslipidemias. Obviously, that would be the first thing. Dr. Bellos (VO): One would suggest diet and exercise. We know from non-HIV-infected patients that that is not necessarily the most efficacious approach. Then, one would need to look at potentially adding medications to those patients, such as the statin drugs, in an attempt to lower their cholesterol, and raise their HDLs. One of the things that I have actually found to be helpful with those patients is the addition of omega-3 fatty acids, and again, anecdotally, what we have done-and actually, the cardiologists are recommending it as well in our area-is the addition of omega-3 fatty acids to those regimens, in an attempt to try to increase HDLs, and lower LDLs.   See Slide Dr. Bellos (OC): ...I try sort of non-medical, or non-pharmaceutical remedies, initially, and then, if I'm unsuccessful, we move ahead to therapy. And I say that with a caveat being that if someone has cholesterol of 385 or 300, that's not somebody that I'm likely to be able to control with a non--medical therapy. That's someone who is probably going to necessitate a statin. Dr. Kwakwa (OC): This may go counter to what I read in the literature, but the dyslipidemias that I tend to see in my practice are dyslipidemias that generally do not respond well to switching, and there are very few of them. I think the reason we do not see many dyslipidemias in our practice is because we are very aggressive about working very closely with patients to adopt lifestyles and habits that will not aggravate or cause dyslipidemias. Dr. Kwakwa (VO): We tend to identify it very early, and treat very aggressively, and so, we tend to treat many of our dyslipidemias with statins, with fibrates, and with lifestyles changes, and have been fairly successful doing that. In the cases where we are unable to control dyslipidemias in that way, we do switch, but again, we have not been very successful there.   See Slide Dr. Bellos (OC): Now, there are some of the newer protease inhibitors that have been shown to actually be somewhat lipid-friendly-for example, fosamprenavir, or Lexiva, has actually been shown to be relatively lipid-friendly, in terms of not seeing the significant increases in triglycerides and cholesterol that one would expect to see, and Dr. Bellos (VO): If you look at the trials NEAT and SOLO, which were done with fosamprenavir and boosted fosamprenavir, the amount of hypertriglyceridemia that one saw, the hypercholesterolemia that one saw was not statistically significant. In fact, if you look at HDLs and total cholesterol with respect to the INCEPT guidelines in those two trials, the patients actually fared relatively well. If you look at patients who actually initiated therapy with a statin after initiation of the trial, the numbers were very low. It was about 2% in each arm in each trial,   See Slide   See Slide Dr. Bellos (OC): ...and I think that is relatively significant in terms of having a protease inhibitor, which has typically been known to cause elevations in lipid panels. Dr. Wohlfeiler (OC): That's another big reason to make switches in medications. Those primarily are switches associated with protease inhibitors. And I've had to take a lot of patients off of specific protease inhibitors. Probably most commonly would be to take them off of lopinavir/ ritonavir (Kaletra) because of lipids that have gone really high, that we have not been able to control really any other way, certainly some of the newer protease inhibitors like fosamprenavir and atazanavir appear to be much more lipid friendly. And so I have had to switch a number of patients. I've got one patient whose cholesterol went to 800 on a lopinavir-based regimen. I've seen triglycerides as high as 5,000. And those are scary numbers. And those are not numbers that are going to get into normal range with the use of a statin or a fibrate. Announcer (VO): Grade 3 and 4 lipid elevations observed with lopinavir can occur in both treatment-naïve and treatment-experienced patients. Those who are on their second or third regimen containing lopinavir have a higher incidence compared to patients receiving initial treatment with lopinavir.   See Slide Dr. Bellos (OC): ...a lot of the patients I follow I have followed long-term, so I have really had the ability to look at their lipid panels over time, and I know their family histories, and know their risk factors for cardiac disease, such as smoking, obesity, lack of excise, diet-those kinds of things, so I really have established that sort of core with those patients, so that I really, in my own mind, can make the judgment as to whether changing the regimen or treatment of the dyslipidemia is what I need to do, and in a lot of instances, I am actually able to change the regimen, and make some improvement in the dyslipidemia that we still have to go ahead and treat, but I am actually able to use, for example, lower doses of the statins, or niacin, or those kinds of drugs, so that we have less potential for toxicity. Dr. Bellos (VO): Well, the two drugs that are currently available in terms of the protease inhibitors are Lexiva and atazanavir. Both of those drugs have been shown to be lipid-friendly, and they both can be given once daily, boosted or unboosted, with ritonavir, so my first choice would be-especially now that fosamprenavir is available as a 700 mg capsule-would probably be to go to something like fosamprenavir.   See Slide Dr. Bellos (VO): There are essentially three particular dosing regimens that can be used with fosamprenavir. It can be given as two tablets twice daily. It can be given twice daily with one fosamprenavir boosted by one ritonavir, or it can be in the total dosing of a QD regimen, with ritonavir capsules given once.   See Slide Dr. Bellos (OC): You don't see the significant increases in cholesterol and triglycerides that you see with some of the other protease inhibitors when it's boosted.
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