Transcript of The Body's Live Chat on Lipoatrophy (Fat Loss) With Dr. Calvin Cohen
Sponsored by Gilead Sciences
April 26, 2006
This is the sixth chat that The Body has moderated; to see transcripts of previous chats, click here.
Chat Room: Welcome to The Body's live chat on lipoatrophy (fat loss)! Our speaker is HIV physician/researcher Dr. Cal Cohen.
Moderator: This chat will begin shortly; please feel free to begin submitting your questions! (Keep in mind that this is a moderated chat, which means you won't see your question in the chat room until Dr. Cohen answers it.)
Thank you all for coming to The Body's live, interactive chat on lipoatrophy, the loss of fat that some people with HIV experience [from] specific parts of their body (such as the face, arms and legs). Our speaker for tonight's chat on lipoatrophy is Dr. Calvin Cohen, a widely respected and experienced HIV physician/researcher. Dr. Cohen is the research director of the Community Research Initiative of New England; he also teaches at Harvard Medical School.
Question from anonymous: Out of curiosity, just what is the difference between lipoatrophy and lipodystrophy? Or are the terms interchangeable?
Answer from Dr. Calvin Cohen: Great point. Let's start here. Lipodystrophy simply means abnormal fat distribution. [There are] normal fat patterns, and as a result of the research we have done, we have defined abnormal patterns that we've clustered together and called lipodystrophy.
There are in general two abnormalities: One is fat loss, which is what we call lipoatrophy. Then, there are abnormal areas of fat gain, usually called fat hypertrophy. Not everyone who has lipodystrophy has fat loss; some just have fat gain. But in general, if someone has lipodystrophy, someone has some degree of fat loss, or lipoatrophy. Hope that is clearer.
Question from anonymous: I have been looking for a resource that outlines all of the various HIV medications and the extent to which they cause lipoatrophy. Do you know of any such resource? It would great to have one chart that listed medications in columns with headings, such as Severe, Moderate, Mild, Not Known to Cause Lipoatrophy.
Answer from Dr. Calvin Cohen: I am not aware of a table or summary, but no doubt there likely is one on any number of Web sites, this one included. However, I can summarize what a table might say. First, I note you are asking specifically about fat loss, or lipoatrophy. That is distinct from all types of body-shape changes, such as increased fat in the belly or the back of the neck. I point this out since all of the body-shape changes are called lipodystrophy, and in recent years we have learned to separate the drugs that lead to fat loss [from the] drugs that lead to fat gain. It would not be the same list.
So, here's what we now understand based on our studies of people starting HIV medication: Fat loss is linked primarily to some of the nucleoside analog antivirals (NRTIs), specifically the thymidine analogs. More simply, the drug that causes the most fat loss is d4T (stavudine, Zerit) -- the "T" stands for thymidine. In all of the studies on this issue, that single drug is the most common and frequent link to this condition.
The second most common is the other "T" drug, AZT (zidovudine, Retrovir). Unlike d4T, AZT is also a component of a few combination tablets -- such as Combivir (AZT/3TC), as well as Trizivir (AZT/3TC/abacavir). It is fair to say that d4T causes more fat loss than AZT. Certainly we can see it sooner, and perhaps even more severely than what we see with AZT, but both are associated with it. In contrast, most of the other nucleoside analogs we commonly use these days -- tenofovir (Viread), abacavir (Ziagen), 3TC (lamivudine, Epivir) or FTC (emtricitabine, Emtriva) -- are not linked to this condition. (Note: There are some combination tablets of these drugs, including Truvada [tenofovir/FTC] and Epzicom [abacavir/3TC, Epzicom is called Kivexa outside of the United States].)
In our comparative studies, people taking d4T will generally lose limb fat, and this can be noted even in the first year using some of our more sensitive tests and scans. After about three years, the fat loss will be noticeable in perhaps 20 percent of people taking d4T. In contrast, people taking tenofovir after three years will rarely have fat loss; [most in fact will regain their normal fat levels] (since untreated HIV can also cause some lipoatrophy).
Not surprisingly, our tests [show] improvements in restoring normal fat levels in people who switch from d4T or AZT to either tenofovir or abacavir, even after just a few months. Visually, it may take longer to see the benefits, but they are happening based on several studies done so far. These studies find that tenofovir and abacavir are similarly helpful in allowing the body to recover from the fat loss caused by the "T" drugs.
Both FTC and 3TC are considered safe. We have less data on ddI (didanosine, Videx), but we think of it as reasonably safe, perhaps somewhere in between the "T" drugs and these safest ones.
The info we have on the NNRTIs or "non-nukes" like efavirenz (Sustiva, Stocrin) and nevirapine (Viramune) suggest these are also very safe. [We have less information about the role of the protease inhibitors in fat loss], but there is some suggestion that they are a bit more likely than the NNRTIs to contribute to fat loss when taken in some combinations. But protease inhibitors, like the NRTIs, are very varied and there is some reason to expect that some will contribute and some will be safer. However, we're still learning about this class and this issue.
Question from PoohBear: Is it pronounced L-EYE-po-dystrophy (like liposuction) or LIP-o-dystrophy (as in lips)? Thanks!
Answer from Dr. Calvin Cohen: Well, since this is a chat, I suppose you get to pronounce it however you want. However, in our meetings we tend to use the latter version more than the former, but I've heard it both ways. It likely depends on which side of [the] Atlantic Ocean you are on and how you pronounce liposuction since that too can be [pronounced] L-EYE-po or LIP-o!
Question from brick: Hello, Dr. Cohen. Have there been any new discoveries to counter lipodystrophy since the last chat on this subject?
Answer from Dr. Calvin Cohen: In November there was some new information about this issue. First there were two studies showing some benefit for people with fat loss: One was using a supplement called uridine; the other was a study testing pravastatin (Pravachol, Pravigard), a drug that lowers cholesterol. Both showed some interesting benefits in those with fat loss. In February of this year we saw additional new information. One study tested a drug called pioglitazone (Actos), a drug similar in name to rosiglitazone (Avandia). Both of these are used for diabetics. In this pioglitazone study there was benefit to those with fat loss.
After one year, there were improvements in limb fat, and in those not also on d4T, there was even more dramatic limb-fat recovery. The degree of improvement was similar to [that which was] seen when people changed from d4T or AZT to a safer drug like abacavir or tenofovir: a gain of about half in just one year in limb-fat circumference. And so we'll likely hear more about this drug in the years to come. Indeed, we will likely see more studies of these three promising interventions based on these small, but important, studies.
Question from JK: Why has it been so difficult to figure out the reason lipoatrophy can't be reversed?
Answer from Dr. Calvin Cohen: Well, in short, it can be reversed. It just takes a while to recover -- perhaps as much time as it takes to happen, if not more. But in studies of people who switch from drugs like d4T to tenofovir or abacavir, we do see benefits, even in just six months, based on the careful scanning we can do. Now, it may not be visually obvious yet, but in time it seems likely that people will look better as this problem reverses.
Question from Kevin: How can you call pioglitazone a positive development? Patients gained only a pound in one year!
Answer from Dr. Calvin Cohen: Well you describe the average improvement in people who without pioglitazone did not improve at all. Indeed, it is more likely they would further deteriorate. So even a pound in a year is an improvement given the alternative. And while this is frustratingly slow for improvement, some do improve faster, and others in time may improve enough to look better than they did initially. We shall see, but slow improvements are still progress in this field.
Question from Luciano: Is it safe for a non-diabetic to use pioglitazone?
Answer from Dr. Calvin Cohen: We are still learning how to use these drugs safely. One test that we can use instead of blood sugar is a testing of fasting insulin. There are some who may have normal or near-normal glucose but high insulin levels. Some of the studies of these drugs have been done in those with elevated insulin levels only. And, yes, so far these drugs appear safe even when total glucose is still in or near the normal range.
Question from brick: You talk about the drugs that cause lipodystrophy and those that are showing promise [to help reverse it]. Can you explain what is physically happening in the cells when the fat loss occurs?
Answer from Dr. Calvin Cohen: Sure. Under a microscope, fat loss is both a loss of the number of fat cells as well as a loss of fat inside the cells. And the main reason this appears to happen is that the fat cells are not functioning so well. There is a decrease in their mitochondrial function, the powerhouse in the cell. However, there are still ongoing mysteries. For example: Why do fat cells lose fat in some places more than others? Why in the face and arms more than elsewhere? Why do some [people] gain [fat] in the belly while they lose fat in the limbs? Many questions [are] still to be answered.
Question from CMH: What has the experience been with Kaletra (lopinavir/ritonavir)?
Answer from Dr. Calvin Cohen: There is a lot of data about the benefit of Kaletra virologically, but unfortunately less careful data about its impact on lipodystrophy. What we can say is also colored by the fact that many studies of Kaletra also used d4T, which we now know made problems of its own. So for now it seems that Kaletra does OK on average on this issue; perhaps it's not the best, but it certainly can allow people to recover from some of the worst drugs.
Question from anonymous: Is there any information on the new drug classes (like integrase inhibitors or CCR5 blockers) in development in regards to lipoatrophy?
Answer from Dr. Calvin Cohen: No, no information at all. Part of the enthusiasm, however, about these new drugs is that because they work so differently, it would be a major surprise if they led to lipodystrophy. Not that we cannot be surprised; it can happen. However, it seems that drugs that work in very different ways to stop HIV should have different side effects with regard to how they affect us and our cells. So hopefully lipodystrophy [is not one of their side effects]. We have some reason to think this is correct based on the lack of lipodystrophy seen with T-20 (enfuvirtide, Fuzeon).
Of course, we are still in the beginning [stages] of really knowing for sure what good and bad [effects] these newer drugs offer.
Question from anonymous: What are the hematological markers a doctor uses to predict or confirm lipodystrophy/atrophy?
Answer from Dr. Calvin Cohen: Sadly we have few if any blood tests that we can rely on to predict or confirm lipodystrophy. Commonly, most combinations that cause lipodystrophy also cause a rise in the blood triglycerides, but there are exceptions to this. Therefore we do not recommend relying on [tests that measure triglyceride levels]. [This test] is a decent marker, but far from perfect.
There was research into other more specific markers: i.e., tests of mitochondrial function, but none of these have been shown yet to be useful. There is also [research being done] looking at more unusual markers that test inflammation; so far none of these have been shown to be useful.
So for now we are still relying on what we can see both with our eyes and with scans, if needed, to know when there is evidence of lipodystrophy. And, in general, lipodystrophy is an event based more on what we see, rather than blood tests of things we don't see. Since, if it is too subtle to see, we're not sure we have too much reason to worry about it.
Question from anonymous: There seems to be only a little data concerning uridine (NucleomaxX) and its ability to protect mitochondrial DNA in vivo, particularly when a patient is no longer taking the most offending NRTIs. I am no longer on d4T, ddI or AZT, but I have pronounced lipoatrophy in my legs/arms. I have wanted to begin uridine supplementation rather than wait further years for more studies to conclude, but I have no idea what might be a large enough dose to make a difference yet not be overly toxic. Is there any evidence that uridine may help restore adipose cells or only that it may help protect mitochondrial DNA from initial destruction in the ongoing presence of NRTIs? Thank you!
Answer from Dr. Calvin Cohen: You are correct. In fact, there is no data I know of on people not taking one of those drugs and whether uridine is of benefit. This story about uridine is just starting, which is always a frustrating time for those to whom the data do not apply. But work is ongoing to better understand the limits and benefits of this interesting supplement.
Question from Luciano: What do you know about the use of DHEA and L-carnitine to regain fat?
Answer from Dr. Calvin Cohen: I have not seen any great studies of either product. I know there are plenty of stories out there; I read them too. However, I have not seen much about either in a study format that would allow clinicians to understand if the drugs really help, how much they help, when they don't work, and so on. For now, hearing only good news rumors keeps these on the radar, but sometimes it is only because we're hearing half the story.
Question from anonymous: You said that doctors have to rely on their eyes and scans to figure out whether a person has lipoatrophy. Do different doctors have different opinions on what constitutes lipoatrophy or do they all follow some kind of general guideline?
Answer from Dr. Calvin Cohen: One of the biggest challenges in the field of lipodystrophy is having people agree on what it is we are describing. There is little disagreement in the most obvious circumstance: those with severe loss in the cheeks, thighs and elsewhere. The subtler changes are where we can differ. There is work to get a definition standardized, but for now we're still relying more on our collective judgment than some precise measurement. That said, in some studies, our visual judgment is supported by what is seen on the scans, so we can do pretty well overall. Though I agree. As we differ among ourselves, there is room for confusion.
Question from DGGee: Can you speak to the status of therapy using anabolic steroids in addition to a testosterone supplement?
Answer from Dr. Calvin Cohen: One of the challenges in the use of anabolics is that they can contribute to fat loss. While they are often used by people who want more muscle bulk, the downside is that there can be a loss of subcutaneous fat, also called lipoatrophy, which up to a point some people don't object to. Looking lean and muscled is for some a goal. However, for those battling lipoatrophy, anabolics can cause more of it.
Question from brick: You mention uridine as a supplement. Is this available in health-food stores without a prescription?
Answer from Dr. Calvin Cohen: I don't know of any availability in the United States of this supplement. Certainly it's not by prescription. And [let's] be clear that the one study is far from sufficient proof to guide us both for effective use and safety. It was a small study and many details are left still to be described. So I would not suggest polling the Internet yet for this one.
Question from Clint: Do people with more muscle mass than fat suffer as much from lipodystrophy or does body type have nothing to do with it?
Answer from Dr. Calvin Cohen: Body type does [play] some role in the following way: If someone starts with less body fat, those who are thin or well muscled, he or she may show a loss sooner than someone who starts with a lot of fat under the skin. So the rate of loss may not differ. That is based on other factors like CD4 counts, age and to some degree gender. But body type can influence how soon it shows and how obvious it is.
Question from Tcell: You may have mentioned this already, but what is your view on switching off a medication that is working but has the potential to cause trouble? I've been on a regimen that includes AZT for two years and I am doing well. However, I'm worried about problems down the line. Do you see this as a reason to switch sooner rather than later?
Answer from Dr. Calvin Cohen: Great question. If we offer a switch in meds to something that may have benefits in terms of lesser side effects, it is important to switch to meds that are understood to be as effective as what we are replacing. In general, if someone has HIV that is controlled while on AZT, it should also respond to both tenofovir and abacavir, for example. There can be surprises, but that would be a rare outcome. In general, a clinician who offers a switch should know when a switch is likely to work versus when it is too risky to do so.
Question from anonymous: At what CD4 count does fat loss start? Is it possible to have fat loss on the face reversed?
Answer from Dr. Calvin Cohen: First, you are correct; there is an association between the damage done by HIV when untreated and the loss of CD4 cells and lipoatrophy, or fat loss. This has been noted by researchers for several years. It is also fair to say that there is no line or number above which HIV does not cause damage for some or below which fat loss starts. It is likely to be a bit more complex than this. Perhaps it is easiest to consider this as a process that happens slowly, but can be [persistent] over time. The longer HIV [is left] untreated, the more likely someone will have low CD4 cell counts and the more likely we'll see fat loss, too.
Certainly with a CD4 cell count below 200 and even below 100 in most studies of this issue, fat loss is far more likely than at a count of 500. But on the other hand, someone with a CD4 count of 175 may look fine, while someone else with a CD4 count of 250 may show some signs. There are other factors that play into how visible and apparent this fat loss can be. These factors include age, gender, and how much fat was present before HIV infection. It is also clear that some [with HIV will go] untreated for 10 years and [have] a good CD4 count if they have a lower viral load, while another person will only have HIV for two years with a low viral load, since they acquired a more aggressive strain of HIV. This too may impact how likely we'll see fat loss at any given count.
As for reversing fat loss, yes, it is possible to do so. One way is to do it the same way HIV-negative people alter their appearance, with various approaches like cosmetic surgery. For example, there are products that are approved by governmental authorities that are considered safe and effective to be injected by a surgeon under the skin. These products can fill in the spaces left by the loss of fat, restoring a normal appearance. [However], these products don't fix the underlying problem as they are not treating HIV [or] the problems HIV is causing, but simply acting to fill in the pockets. One such product in the United States is called Sculptra (poly-L-lactic acid, Sculptra is called New-Fill outside of the United States) and there are others.
Other approaches more directly target the problems that cause fat loss. For example, treating HIV infection with a safe regimen can reverse fat loss. Now this reversal may take a while to be visually noticeable, but in studies we can see the fat returning in a way that is reassuring and should become visually apparent over time. Depending on how much damage was done, it may even take years. But if [fat loss] took years to happen, it should not surprise us that it can take the same amount of time to reverse.
So far, our safest antiviral regimens that effectively control HIV without contributing to fat loss include two NRTIs plus an NNRTI. The two NRTIs we are using are tenofovir plus FTC (also contained in the combination drug Truvada) and Epzicom; these combinations are the best at controlling HIV without creating fat loss. As for the NNRTIs, we have great data about avoiding fat loss when using efavirenz. We have some data using nevirapine as well.
Question from anonymous: Do you recommend Sculptra for facial fat loss? Also, can it be used for other parts of the body?
Answer from Dr. Calvin Cohen: Sculptra is a challenging drug mainly due to financial issues and limits. Some who want to try it cannot afford either the drug or the surgeon's fee for injecting it, which makes it difficult to use. However, for those fortunate enough to not have financial limits, I have heard of some great results, not universally, but enough to keep it on the list of options.
As for other places, it would be difficult to imagine using it in the arms, thighs or buttocks. I suppose some might consider trying this, but I have not heard of anyone yet giving this a try nor any reports, if they have.
Question from googler: Does AZT cause wasting in everyone? I have not experienced it yet and have been on the same medications for four years.
Answer from Dr. Calvin Cohen: Great point. We are talking about drugs that are more or less likely to cause trouble. But as you point out some people do far better than others. Some have no side effects, while others have more than their share. The reasons for this are in part, explained by genetic factors; it does seem that lipodystrophy has some differences predicted by our genetics; therefore, some will tolerate one drug that others find to be difficult. So apparently you are one of the luckier ones genetically. That said, it might never occur or could just be much slower. Keep your eyes open. As we get older, there can be more vulnerability to side effects that were not a problem in younger years.
Question from anonymous: Can someone have lipoatrophy without having ever been on HIV medication?
Answer from Dr. Calvin Cohen: Yes, this can happen up to a point. As we look at people who are HIV negative, we can see sunken cheeks and other aspects that can look like some of the problems [attributed to] lipoatrophy. Some of it does appear reasonably unique outside of HIV treatment, such as the fat loss of the upper arms and thighs. There are some genetic conditions [that cause this to] occur, but these are uncommon as compared to cheek fat loss. And again, keep in mind that untreated HIV does cause fat loss, [which is] one of the reasons why some advocate treating HIV sooner.
Question from MattB: I've had facial wasting for years. Last year I used a little saved cash to get a few sessions of Sculptra. But after the swelling went down, my face went back to the lipoatrophy look. My doctor says my body didn't produce collagen in response to the injections. Is this true? Why didn't I produce collagen?
Answer from Dr. Calvin Cohen: [It's] hard to say why it did not work for you. However, there is a general point here, which is that we often focus on the average responses while there are some who are not going to respond like the average person does. This can be due to many factors, including how many treatments someone needs as well as issues of technique in getting a prolonged benefit. It is not likely that this drug will work for everyone given that the way it is administered is a skill that is still being learned. So while I don't know why it did not work for you, I am sure you're not alone in your outcome. We're hoping, of course, to find drugs that are more predictable. In time let's hope that is the case.
Question from anonymous: When I read about lipoatrophy, I see that most of the advice and possible solutions/remedies given are things that are not accessible to most Africans who are affected. What is the way forward for this part of the world? We are also highly affected by this condition.
Answer from Dr. Calvin Cohen: There is much inequality in the world of HIV. [There is much that is not available] to many Africans, Indians, Latin Americans and the poor who live in otherwise developed countries. We all agree that resolving this ongoing problem, ensuring the best access in all parts of our world, is one of the stories yet to be satisfactorily written at this 25-year anniversary of the recognition of HIV.
Moderator: Our interactive chat on lipoatrophy (fat loss) has now concluded. Thank you, Dr. Cohen, for taking the time to answer everyone's questions!
Dr. Calvin Cohen: And thanks to all of you for joining me tonight. We have made some progress and I hope for more to come in this ongoing challenge in the care of people with HIV.
Moderator: To those of you whose questions we were unable to answer tonight, please try visiting The Body's lipoatrophy information page at www.thebody.com/treat/lipoatrophy.html for more information, or ask our staff of experts at www.thebody.com/experts.html. Thank you all again. Have a good night!
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