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LATEST UPDATE ON HIV LIPODYSTROPHY: Interview with Dr Grace McComsey
 
 
  Video: https://www.youtube.com/watch?v=juQBV1TIEl4
 
Nelson Vergel:Hello everybody. Nelson Vergel here with Program for Wellness Restoration, a nonprofit that has been in operation since 1994. Our mission is to provide health and wellness education for people living with HIV and also for their caregivers and medical support system.
 
We are very honored today to have Dr. Grace McComsey. She is one of the leaders in lipodystrophy research. Lipodystrophy rules a lot of our lives, in HIV long term survivors like me. And by the way, I have to apologize for my bad cold. My voice is still going in and out. I've been basically after Dr. McComsey for a while, because she not only is a busy woman, but she has really wonderful research that I think most of us don't know much about. So it is time, hopefully, to spread the knowledge about what's happening in lipodystrophy. What are we learning, what are the options.
 
Dr. Grace McComsey has been involved in HIV research for 16 years, 12 of those as an NIH-funded principal investigator. Her work has focused on the investigations on lipodystrophy and metabolic complications in HIV. Her work was paramount in showing the link between nucleoside inhibitor-induced mitochondrial toxicity and lipoatrophy in HIV-infected people. Her work was recognized by the HIV Medical Association of the Infectious Diseases Society of America, with the HIVMA Leader in HIV Research Award. Specifically in recognition for her work in advancing our understanding of lipodystrophy. She has personally led a number of studies, including several multi-center investigating different means to prevent and treat fat alterations in HIV, including uridine supplements, rosiglitazone, statins, and modulation of antiviral therapy dose and type. She has also led several SDG studies showing that central fat accumulation continues to be a major problem threatening the success of current HIV treatment. We're going to talk about that today. That's our focus.
 
In the last 12 years, she has led Case HIV Metabolic Center, which is recognized for clinical and translational studies highlighting the pathogenesis and management of metabolic and cardiovascular complications in HIV. Over the last few years, she has been focusing on elucidating the role of inflammation and immune activation related to co-morbidities in HIV.
 
Welcome, Dr. McComsey. Thank you so much for agreeing to do this interview. Dr G McComsey:Thank you, Nelson. It's good to be with you.
 
Nelson Vergel:Yeah, we're going to start because we have a lot of questions. Can you describe your previous work in lipodystrophy, briefly, before we get into more direct questions on the actual results?
 
Dr G McComsey:Sure. I started working on metabolic complications in lipodystrophy for more than 15 years. At that point, if you remember, we had started to recognize that even if someone is on medication, undetectable, they started to suffer from this variety of fat problems. We called it lipodystrophy. Now we try not to call it lipodystrophy, and I'll tell you why in a second. So we called it lipodystrophy, and we noticed that people were gaining lots of central fat, losing a lot of peripheral fat. I started to work on trying to understand why.
 
As you mentioned, my group and others have found that mitochondrial toxicity was at the forefront of lipoatrophy. And I think that's a very important distinction is that lipoatrophy, or the peripheral fat loss in the limbs and the buttocks area, is very different than lipohypertrophy, which is the accumulation of fat centrally. So although we found that mitochondrial toxicity played a major role in lipoatrophy, that really was not the case with lipohypertrophy. It remains a huge enigma. We still don't know what causes it. So that's why when we use lipodystrophy, it's kind of like, that or that. It's not clear what it means. So we can call it lipoatrophy for the peripheral fat loss, and lipohypertrophy for the central accumulation.
 
As you mentioned, I led several studies to try to not only understand it, but even prevent lipoatrophy. For the most part, we tried to regenerate in a way or make the mitochondria more functional with different medications like uridine we tried under ACTG. Unfortunately nothing seemed to work. The best thing for lipoatrophy is to prevent it. Fortunately, with not using AZT, D14, ddI, those old toxic medications, the incidence of new cases really went down. I never want to forget that people are still living with lipoatrophy. That's sad because these are the long-term survivors who had bad drugs, had lipoatrophy, and still live with it. So that research should still be ongoing. Not much is happening there now.
 
The other facet, the lipohypertrophy or the accumulation of fat, that's a booming area and it should be. Because we're recognizing more and more that a lot of people, the majority, who start medications are having some kind of fat gains that we used to call return to health and hope that that's a good sign. You know, they're healthier. Now we know it's a little overshooting. It's not just return to health; it's too much of a good thing, perhaps. So we went from worrying about underweight wasting to now worrying about obesity and central fat accumulation. That area remains very active in research.
 
Nelson Vergel:So you don't think that there is actually lack of activity in lipohypertrophy research?
 
Dr G McComsey:Yeah, the lipohypertrophy, the accumulation, there's a lot happening. But the atrophy, no. It's like we forgot that there's still a large number of people living with it, so there's not much trials. There's not much interest, unfortunately, in new studies to try to decipher what can we do about these people.
 
Nelson Vergel:Yeah. We have two facial fillers that are approved by the FDA, but many people don't have access because of ...
 
Dr G McComsey:Yeah. Sure.
 
Nelson Vergel:But anyways, so tell us a little bit about the very interesting study, the ACTG 85260s that you presented at CROI last year. And so this study, when you guys presented it, I was blown away by learning that the expectation that I had that integrase inhibitors would cause less lipohypertrophy.
 
Dr G McComsey:You and the rest of us, I guess. One of the misconceptions of lipodystrophy - in particular the hypertrophy - is that it's due to protease inhibitors. So ACTG 5260 is a substudy of a larger parent ACTG study called 5257. If you recall, this is a study where they took large number of previously naïve patients. Never been on drugs. They started them on one of three different regimens. Two had protease inhibitors, one a ritonavir-boosted atazanavir, the other one ritonavir-boosted darunavir, and the third regimen was an integrase inhibitor called raltegravir. Now what we knew about integrase inhibitors at that point is that they were better on lipids, so more lipid-friendly. Better on insulin resistance.
 
Body Composition Changes after Initiation of Raltegravir or Protease Inhibitors..... - (03/16/15)
 
So everybody's hope was that, in term of fat gains, we were going to see a differential effect with better effect of integrase inhibitors. That's not what we found. We found that all three arms had over two years' time, which as you know is a short time when you talk about HIV treatment, in two years' time there were 25% overall increase in visceral abdominal fat. That was measured by CAT scans, so is a pretty precise measurement of deep fat. That's the fat that causes diabetes, problem with heart disease. So the protease inhibitors, both atazanavir or darunavir, didn't do any worse than the integrase inhibitor raltegravir. So that was a disappointment, that ... Regardless what you use, it's not just protease inhibitors. Even integrase seems to do the same thing.
 
Nelson Vergel:Yeah, that was definitely not good news for the community. We really are kind of depressed about the fact that there is very little we can do except what we always hear, exercise, nutrition. And there's actually the approved product that we can talk about later on too. But, I also ... The surprising thing to me also, it's like a small proportion of patients also had fat loss. That really shocked me because obviously most people gain fat in the visceral area and even under the skin. But this subset of patients actually lost fat. So can you ... Have you been able to identify why these patients responded differently?
 
Dr G McComsey:Yes. I apologize for the background noise. We have a plane in the sky here. About 15% of patients or of subjects had some kind of limb fat loss. Remember, we were looking at that to see about lipoatrophy, about the concern about ... Because we still have a little bit of lipoatrophy on some people. The individuals that lost limb fat, about 15%, belonged to all three regimens, so it wasn't one regimen or the other. They were all undetectable, so that was important. It's not like they didn't respond to their medication so didn't take it. They had a good CD4 response and they lost visceral fat as well as muscle. So they lost fat everywhere.
 
We tried to understand why this group lost fat everywhere despite the fact that they responded to treatment. The only thing that was different is there was higher use of marijuana in that group. Now you and I know, people say they take marijuana for increasing their appetite, decreasing their nausea ... They feel better, they eat more. We didn't expect that they would lose. But after we found that, I did look at the literature, and there has been a couple papers describing that people, even without pain, even without a reason for taking the marijuana, that could have led to weight loss. People who use marijuana seem to exhibit some loss of fat. That's unclear even outside of HIV. But we found that was very interesting and that for sure needs to be studied, because a lot of our clinic patients take marijuana for one reason or the other. So that needs to be studied further.
 
Nelson Vergel:And I didn't even include this but I thought about this. Could ... You have a hypothesis, I guess not only you but the research world, that maybe the immune system, the immune cells like macrophages, are inside fat cells and something happens to them. Can you explain that hypothesis?
 
Dr G McComsey:Yeah, we think ... Now, remember, that's a hypothesis really for lipoatrophy. In term of mechanism, we still do not know. And I think that's important. You hear hypotheses here and there. We've been wrong on HIV before, as you know. So we're studying that. I know we're doing some studies, others are, to try to understand if that's true or not. But the hypothesis, it's called metabolic endotoxemia. So what it is is ... HIV is known, early on after you acquire HIV, to lead to gut integrity issues. It changes the fecal microbiome, and your gut cells are not working as well. There is some leakage of bacterial product into the circulation.
 
It's known from outside of HIV, from obesity, from diabetes. People who don't have the HIV virus, it is known that when you have leakage of bacteria, it goes to the fat cells. It causes insulin resistance and it causes the macrophage to be attracted to the fat cells and become activated, leading to a lot of fixation of cytokines, lots of inflammation. And it becomes a vicious cycle because some of these called chemokines will attract more inflamed cells to the fat, creating more cytokines. You have this inflammatory milieu and some of the virus may be trapped there.
 
In terms of pure research, some people now are looking seriously at fat being one of the reservoirs that's hard to eradicate. Not only we're worried about the fat becoming hypertrophic, increasing in size because of the hypertrophy that we're talking about, but also about the fat tissue being the cause of inflammation in the blood as well as being a hinder for cure agenda. So the fat itself, as a tissue, is gaining lots of popularity now and large groups are working on that.
 
Nelson Vergel:Good, good. So when it comes to visceral fat, you mentioned its link to diabetes, metabolic disorders, maybe cardiovascular disease, etc. Is anybody, including you obviously, getting any funding to look at the long-term consequences of increased adipose tissue in the visceral area for HIV?
 
Dr G McComsey:Yes. So luckily actually, even within the HIV population there has been studies linking directly visceral adiposity to increased mortality, even after adjusting for everything else. To increased cardiovascular risk as well as to diabetes. So we already have data to tell us that it's not only a cosmetic issue. It is increasing the risk of our patients dying, of our patients getting sick from diabetes and heart disease. It went beyond the initial phase where people would say, "Ah, it's just a cosmetic, you know ... " I've heard some silly comments like, "Oh, they're happy to be alive, it's better than to be wasted."
 
To now understanding that that's a major problem. This is not just a cosmetic issue. So there is data already, but the funding, the sponsors ... Despite us researchers being very excited still about this field, it really is becoming harder and harder to get any funding for doing fat work. Cardiovascular is a different area, because the NIH Institute that funds cardiovascular disease is very interested in learning more about what we can do to decrease risk of heart disease. But unfortunately, it seems like the fat is not as popular for these sponsors as other areas that may seem more sexy to them, like cure. It's all important and of course we want a cure, but you can't forget about something that people are living with every day in the clinic, versus just hoping for a cure down the road.
 
Nelson Vergel:Yeah, and I think that whatever we learn with regards to visceral fat research can be applied to many other pathologies, so it's not like we're spending money ... If we spend money on visceral fat in HIV, it will probably benefit people with diabetes, people with different conditions too. So I hope that lipodystrophy research is not dead. Some of us in the activist world, we used to go to a lipodystrophy meeting every year. They changed the name of the meetings so I knew there was something there. And fewer and fewer papers, because I do follow this field, are being published now.
 
So, what can we do as community and as activists to ... Because we do advocate for NIH funding. I think it is time to reactivate that part of HIV research. I just got in from Fort Lauderdale and I went to Palm Springs and a lot of people there, that's their main complaint. Not only because they have a big belly, but also they feel bloated, they're out of breath a lot. Going up and down the stairs is a big issue. Even tying their shoes is a big issue. They've tried exercise, they're working out, they're doing everything. It's not like they're just sitting in front of the TV. So it's very frustrating ...
 
Dr G McComsey:No, you're right. And something very important is the emotional aspect of this visceral fat accumulation. It has been linked to lower self-esteem, to increased depression. Depression is already very common in our clinic patients so we don't want something else that may make their life more miserable. You have an undetectable viral load, you're happy with how you're doing, but then you feel really bad. You're right, that's not a success. It's not about numbers. It's about the whole picture.
 
Nelson Vergel:Yeah. And in your clinical practice, when you have a discussion or conversation with a patient with lipohypertrophy, what is that discussion like? Dr G McComsey:You know, the toughest discussion is for people who present for treatment. How do much do you tell them? Because you don't want to scare them a lot, to say that you're going to gain 25% of your baseline visceral fat. Because unlike the old days, people are not wasted. They start medication sometimes overweight already, so you don't want to scare them too much. But at the same time you need them to take their medication and be aware that more than anybody else, lifestyle changes are important. Diet is important with two things that I tell people to focus on. Sugar and saturated fat. These are the two things, even outside of HIV, have been shown to promote visceral fat more than anything else. It's not about just the calories. It's what you eat. So saturated fat and sugar, very important when people are starting medication, to try to adhere to a good diet to see if that could prevent some of the fat accumulation.
 
Other thing is exercise. Exercise is important. Not just for fat, visceral fat, but even to decrease inflammation in the blood. It has a lot of different benefits. And it's so hard when you have a very big gut to exercise at that point. So it's important to start even before you have visceral adiposity increase. Make it easier for you. Start early. Start when you have maybe mild symptoms, but don't wait until you have such an increase in your abdominal fat, because it will become harder to exercise of course. Then at that point there's excess fat it would become really hard to get rid of it.
 
Now exercise in HIV, that's the other sad thing in a way. A lot of us, including myself twice, tried to get funding for large exercise study. Believe it or not, there is no good data with exercise. There is some short, small studies taking few people, usually in the range of 16 to 20, making them exercise and then looking at some blood markers. We have very limited data. It's good data. It's telling us that yes, we seem to see the benefit that we see outside of HIV. But we need better exercise studies to tell us what type of exercise. How about if you combine exercise with having low-sugar diet. Can that improve better? So we need research to focus on exercise, focus on diet as well, and not say, "Oh, just take the data from outside of HIV, you'll be fine." I think we learned that our population is different. There's a lot that are different. The virus itself, the inflammation caused by the virus, medications that they're taking ... So we need to study diet and exercise in HIV, not just rely on the data from outside.
 
One other type of fat we didn't talk about but I think it's very important to mention, is the fact that when I say visceral adiposity and lipohypertrophy, it's not only the fat in the abdomen. It could be in the liver, could be in the muscle. Now we're recognizing that fatty liver, meaning fat in the liver, can promote inflammation and lead to cirrhosis at the end. Liver disease from that extra fat is also very important.
 
You hear more at meetings now about hepatic steatosis. We're recognizing that that excess fat seems to be in a lot of other places, even around the heart. We have some studies looking at epicardial fat around the heart. There's a lot of it. It's linked to inflammation, and it's linked to visceral adiposity in the belly. Fat is accumulating in a lot of odd places that we know increase the risk of death, of heart disease, of frailty. Fat is causing lots of trouble in our population.
 
Nelson Vergel:How about hormones, like growth hormone or testosterone or thyroid? Some people may have a low thyroid function.
 
Dr G McComsey:Sure, sure. One of the first tests that we do right when people present with a big accumulation of the abdominal fat is to make sure they're not hypothyroid, they don't have excess cortisol. I can tell you I do these tests in the clinic but I almost never find that that's the cause. We do need studies, large studies, looking at these hormones. That has not been done at a scale that I can tell you we know what happens if someone starts medication. Do different medications have different effects on these hormones? We don't know that. That's sad, after all this time, we still don't because there's not much interest in looking at different hormones in HIV.
 
So we don't know. But what we know is growth hormone deficiency, that seemed to cause at least some of the lipohypertrophy. So there is some growth hormone deficiency in people who accumulate a lot of fat. Not all of them, but higher frequency than the general HIV population. We know that the only FDA-approved medication for lipohypertrophy is the growth hormone-releasing factor. It's a medication ... Unfortunately it's injectable. You have to inject it subcutaneously every day. But it really helps to mimic the release of growth hormone, the physiologic release of growth hormone.
 
And what happened in studies using this product is that visceral abdominal tissue really went down in the majority of people. Not everybody; some people are resistant to it. Even you give it to them, they don't have any effect. But in most of the people, they did see a decrease in visceral adiposity. The problem with this medication, beside the fact it's injectable every day, very expensive, is that as soon as you stop it, few weeks later, you lost all the benefit that you had gained. So you can use it for a long time and be happy, but you can't stop it. It's not a treatment per se. It's just a way to try to maintain lower visceral adiposity. It's not perfect. It's something to offer for the most serious cases, but it's really not the solution.
 
Nelson Vergel:And it's the only product approved for this use.
 
Dr G McComsey:Correct.
 
Nelson Vergel:And I want to make sure that the audience understands that we have a growth hormone product called Serostim that was approved for HIV wasting, and we have a growth hormone-releasing factor, a releasing hormone called EGRIFTA®, which is approved for abdominal fat. So there are two growth hormone products that should not be confused, because they're approved for different reasons. One is Serostim, the other one's EGRIFTA®.
 
How about metformin? Data on this drug seems a little bit all over the place, but ... Dr G McComsey:There were good studies with metformin in the era when we were worried about lipoatrophy more. What happened is, people who take metformin, like diabetics, will lose weight, will lose fat from everywhere. But the problem is, if you have lipoatrophy ... So if you're worried about not losing more fat in your legs, arms or face, metformin may exacerbate that. So yes, you lose fat from everywhere, but it could be from areas you don't want to lose fat from if you have lipoatrophy.
 
It's not a good treatment. Some studies that were done early on in the epidemic, looking specifically at visceral fat, not just at BMI or weight, showed that the visceral fat did not change much with metformin. Again, you're losing overall weight, but not in the places that you want. And you may lose some peripheral fat that you don't want to lose if you have lipoatrophy. I would not recommend metformin for fat changes. It's really not approved, nor work for that indication.
 
Nelson Vergel:I'm taking it and I like it. I've lost half an inch of waist circumference, but that's another story. And I don't have ...
 
Dr G McComsey:Good for you. You probably exercise too, right?
 
Nelson Vergel:Yeah, of course. Nutrition, exercise ... I do take testosterone replacement and metformin. You know, I'm a pharmaceutical android, I call it.
 
Do you recommend ... And this is something I've seen out there that is not being done for patients coming in, especially naïve patients ... Body measurements, at least waist circumference? At baseline, at least to be able to justify a prescription later on if they do need it?
 
Dr G McComsey:Yeah, I do. I do just waist circumference. Unfortunately, like any other subjective test, depends who does it. It may be different than other ... But luckily in our clinic we have a dietician, so if we want to do anthropometrics or measurements, we have someone who's the same person who can do them serially for us.
 
And you're right, I do it just because not it's the best test, but it's the best available one. I can't get a DEXA scan or a CAT scan to look at fat in my clinic because insurances don't pay for that. So the best I have is looking at weight, BMI obviously adjusted for height, and also looking at waist circumference. Better than nothing. Nelson Vergel:I am one of those crazy patients ... Well, I'm an activist, and I also have a very friendly, good doctor that likes to learn through me. So I got a CT scan of one slice at the L4-L5 level. It was very depressing to see the results. I thought it was a little better. And it was really surprising to see how much visceral fat I had in that CT scan. It costed $250, so that's out-of-pocket money that I spent just to find out ... I wanted to see if it's organ size issue, you know. People say sometimes when you do testosterone, your organs grow. No, this was visceral fat. So that was a little humbling for me.
 
Let's switch now to ... It seems like naïve patients that come in with viral load over 100,000 tend to gain a little more fat than those that have under 100,000. That may have to do with the immune response, inflammation, etc. How do we deal with that? Is there anyone looking at anti-inflammatory agents, do we start it the moment that you start antiretrovirals? Is that a bad idea? I'm sure it's come across your mind or everybody else's, right?
 
Dr G McComsey:Yes. No, no, no. I'll get to that. That's a very important question. But let me mention the whole story with the viral load. In that ACTG study that we mentioned, 5260, as well as in a couple of other studies I did, we had noticed and reported that viral load at baseline is a predictor of fat gains. If you have a high viral load ... And in that study, 5260, we found that people who screened with a viral load above 100,000 had two to three times the gain in fat than people who started with lower viral load. So definitely starting treatment with HIV early on, when the viral load is still low, when the CD4 is high, is better in terms of not gaining as much fat.
 
Like everything else, all the complications including bones, as you know ... It's always better to start treatment right away. Don't wait until the disease is advanced. However, obviously, some people are living with it, they don't know they have it. So you're still going to have some people who present with very high viral load. They are at risk of gaining a lot of visceral fat.
 
What you're asking is a great question, actually, that we're thinking about. What would be an agent to try to give them to prevent that change in fat? So the same thinking that we did with the vitamin D and calcium study to prevent the bone loss when you start medication, similar thinking. What can we do? So far our thinking is more toward diet and exercise, and I'll tell you why. Because when you start someone on medication, they want one pill, one a day. They're not used to taking pills. It's been really hard trying to get them to take even calcium and vitamin D for the bones, because people are not used to taking pills. So someone healthy, and now being told, you know, take more pills, or enter in a randomized placebo control study, it's very hard.
 
What we're thinking and planning, if it gets funded, is to do a lifestyle intervention at the time you're starting medication. So randomize people, do a couple different interventions to see if that could safely prevent some of the fat gains mainly in the high-risk patients, those with low CD4 or high viral load. So it's a very interesting question, and some people are thinking more in terms of statin or other medications that could improve immune activation. What would happen is ... If along with their first line HIV medication, you give an agent that improves immune activation, specifically monocyte activation, can you prevent the gains in fat? It is harder to sell, again, just because it's hard to sell a study for someone healthy, just having to take daily medication now. It's really tough population to do a study on. There are people thinking about doing ... For me, my group, we're still thinking more lifestyle intervention at that stage, early on in the disease.
 
But speaking of statin, for example, we did this study that we published several papers from, using statin in people who do not need statin. So they have normal lipids, low LDL cholesterol. Gave them statin to see what it does to their cardiovascular risk. We found a significant decrease in monocyte activation. So people who are on treatment, undetectable viral load, if they took statin, it did improve monocyte activation, even T-cell activation, several inflammation markers, their cardiovascular parameters like carotid IMT.
 
However, it did nothing to the fat. Statin, even though it improved immune activation, it did not affect trunk fat or central fat, nor peripheral fat. That was a disappointment because we were hoping by changing immune activation that we would be able to shrink some of the central fat. Now, to note, that study did not target people who had lipohypertrophy. It was all comers. In fact, most of our patients did not have a lot of visceral fat. But nonetheless, we were hoping that we would be able to show some hint that statin may improve visceral adiposity. We did not see that.
 
Nelson Vergel:How about women? The data in most studies is mostly male. Mostly white males. Can we extrapolate the data to women too?
 
Dr G McComsey:Yes. So we shouldn't extrapolate, right? Because women really are different, so they should be studied. But you're right, in our ACTG study we had only 11% females. Very, very small sample size. However, I want to refer you to a presentation that I was part of, I was the senior author, that we presented at CROI. The first author was Sara Bares. Looking at three large ACTG studies, all naïve, so taking people who are naïve to meds and randomize them to their first regimen. We did look at a large number of females versus males.
 
What we found in that CROI presentation, what we reported, is that females gain more fat, more ... I should say BMI or more weight than males, regardless where they start. So whether they start obese, whether they start with a normal BMI ... Regardless of the BMI at baseline, women get more fat gains or more weight gains than men. I think that is important because like you said, every study has so few women that they were lost among all the males in the study. But now we have evidence from this study that gains in weight are more prominent and more worrisome perhaps in females. Because even when they start with the overweight or obese category, they still gain more than males.
 
There was another presentation, a follow-up from our study, the ACTG study, that looked at race. Using the large parent study, 5257, first author was Priya Bhagwat, one of our team members ... So Priya reported at CROI as well that nonwhite race was a risk factor in severe weight gain. We call severe weight gain gaining more than 10% of your baseline weight. Being nonwhite was a risk factor, as well as being female, in gaining more weight. So yes, I think racial differences, sex differences, are important. More and more we're doing studies to try to define the subpopulations who seem to suffer more from the fat and weight gains.
 
Nelson Vergel:Yeah, I was thinking ... The first report on lipodystrophy, I remember it was like 1997, so it's been 20 years. In 20 years obviously we've learned a lot. We have a lot more questions than answers. But it's only been 20 years. Twenty years is not a very long time in research. But we're hoping ... And hopefully the research community, the activists, can advocate for more research. Obviously we're going through another change in administration, so that could be another factor that we're all concerned about.
 
One last question, because I know you have to go soon to another meeting. This is probably one of the most important ones. Outside HIV, in any work that is being done on visceral fat, has any study actually proven that lowering visceral fat, decreasing visceral fat, actually reduces cardiovascular risk or mortality? Morbidities? We probably don't have that data in HIV, right, but ...
 
Dr G McComsey:No, no, we don't have anything close in HIV. But outside of HIV, yes.
There has been some studies looking at even weight decrease. Remember, when you do studies like that, you want to look at end points like mortality or clinical heart disease. You need large number of people. So that's why you don't have large studies with CAT scans on everybody. You need thousands. We don't have that data in HIV, and we have very little data outside of HIV using CAT scans.
 
But we do have such data with weight loss and change in your risk of heart disease or your likelihood of dying or heart disease. So we can extrapolate that to visceral fat, but you're right. Using CAT scan, we don't have large studies, even in the general population, telling us that if you go down by, you know, 5%, is that really important in decreasing your risk of dying or heart disease? We don't have that, but we have data on decrease in weight and improving your risk of heart disease. But not really decrease in visceral fat. A lot of times we extrapolate because when you decrease weight, some of it is visceral fat. But your question is a great one. We don't have that on visceral fat and decreasing risk of dying or clinical cardiovascular disease events.
 
There's a lot that needs to be known, not just in HIV, even in the general population. Definitely in HIV, that is a area that is booming in terms of the hypertrophy. As much as the lipoatrophy seems to be dying in terms of research, the hypertrophy there's a lot of activity on. If we get activists to help us and convince the sponsors like the government and industry even that it's an important area, I think you'll see more and more really good studies in that field.
 
Industry for instance, because their drug is the same than the rest, it's like nobody is interested in it, right? That's like the worst outcome when you have one drug that causes the same fat issues than the rest. Anybody from industry is going to say, "Why am I putting the money in that?" So unfortunately for the field, industry funding has gone down. I have to fight with a lot of collaborators within industry about adding DEXA scans in the study. And they're like, "Oh, it's too complicated, you know. We can't do it. There are so many sides." So I think activism, not only toward government funding but even industry, to make them understand that yeah, maybe your drug is not worse than the rest, but you need to contribute to money toward that research. That is important. That could help a lot.
 
Nelson Vergel:I think every phase 3 study of HIV medications, ARVs, should have a substudy with a DEXA, a full body DEXA [inaudible 00:44:01] one slice CT. We've been pushing for that for the last few years and like you said, there's a lot of pushback. But the FDA should require that as part of a phase 3. You want to get your drug approved? Fine. You need to generate some data on that. So, you know, we're getting closer to that requirement being put by the FDA. Since, obviously ...
 
Dr G McComsey:I really hope so, actually. I hope so because we need that data and it should be required, because that is important aspect of the efficacy of a drug. It's not just about viral load, CD4, it's much more than that.
 
Nelson Vergel:Yeah. Well, I really, really appreciate your time. I have great admiration for your work. I know it is difficult to get the funding, but you keep doing it anyways. Don't ever get tired of this, because we ...
 
Dr G McComsey:No, no, I won't. That's what drives me to come to work every day. That type of research is my passion and that's why I keep doing it and keep trying.
 
Nelson Vergel:Well, thank you so much. I will probably send you a few questions later on. We are going to be posting this on YouTube and also on thebody.com and on powerusa.org, and people usually write comments or questions. Sometimes they get really interesting and I may bother you in the future with a few of them.
 
Dr G McComsey:Absolutely. Happy to help.
 
Nelson Vergel:Thanks again.
Dr G McComsey:Thank you. Thank you very much. All right. Bye.

 
 
 
 
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