Update on Body Shape Changes and HIV

This Month in HIV: 2009 Update on Body Shape Changes and HIV
A Conversation With Dr. Donald Kotler and Patient Activist Nelson Vergel

April 2009




From TheBody.com


Body shape changes are some of the most frustrating complications of HIV and HIV medications. Whether it's the loss of cheeks or the sudden swollen midsection, people with HIV have been mostly dealing silently with these issues since there are few treatments available. In This Month in HIV, HIV activist and long-time survivor Nelson Vergel leads a discussion with Donald Kotler, M.D., who is an expert on metabolic complications and HIV. They will fill us in on some of the latest updates on this issue.

Nelson Vergel: Hi, Bonnie. Thanks for having me here. And thanks to Dr. Kotler for joining us.

Dr. Kotler, I'd like to start with some basic questions, if you don't mind, to cover the basics about body changes and HIV.

In your opinion, how widespread are body changes in the HIV-positive population? Is there any way that somebody who was recently diagnosed with HIV can know how probable it is that he or she will experience body changes?

Dr. Donald Kotler: That's two questions.

The first one: How frequent are the body shape changes?

The answer is that it depends which shape you're talking about. Some people gain body fat, and others lose body fat. Of the people who gain body fat, for example in the belly, or behind the neck, it's about one-third of patients who have that kind of problem.

In terms of losing body fat and getting really skinny legs, or the skinny face that people notice that's so stigmatizing, in the old days it was almost everybody, and currently it's not many people.

With the change in the antivirals, specifically the stopping of the use of stavudine [d4T, Zerit] and limiting the use of zidovudine [AZT, Retrovir; this drug is also included in Combivir and Trizivir], many fewer people get really thin from lipodystrophy.

Now, the second question: Is there any way that somebody recently diagnosed can avoid these issues?

I gave part of the answer. You can avoid the loss of fat by the choice of medications. Very few people in the United States are taking the medications that will cause body fat loss.

A way of preventing body fat gain was shown about a year and a half ago at the international meeting in Sydney, Australia. Limiting the amount of weight that's gained as people start antivirals will limit the amount of fat that ends up in the belly.1

Nelson Vergel: How do we actually limit the amount of weight that people gain when they start HIV medications?

Dr. Donald Kotler: That's a good question. In the study, which was from Brazil, they use what's called the NCEP [National Cholesterol Education Program] diet. [NCEP was launched in November 1985 by the National Institutes of Health to help reduce illness and death from coronary heart disease in the United States.] It's a healthy diet for somebody with heart disease; it asks people to moderate carbohydrates, decrease fat and consume more fiber. So you tend not to eat things that are so rich and so dense in calories.

It's a standard type of diet for people with heart disease. At least in the study that was presented, people who started their first regimen, plus the diet, gained much less weight -- their cholesterol didn't go up nearly as much and their belly didn't get nearly as big as people who were allowed to eat whatever they wanted.

Nelson Vergel: Dr. Kotler, another issue is the actual word that we use for these changes. People have been using the word "lipodystrophy" for a long time. Is that still a correct word for what's happening in HIV?

Dr. Donald Kotler: Not really, though when you say it, everybody knows what you're talking about. So you could probably get away with it. But lipodystrophy, the classic lipodystrophy, really referred to genetic problems. It was something that people were born with that, as they developed, would show the wasting, would show the thinning of the skin in their face and arms and legs, etc.

The term lipodystrophy with respect to people who are HIV infected is used to mean anything -- fat loss or fat gain, which are not necessarily related, diabetes or high cholesterol, which, once again, may or may not be related to any of the other problems.

We would probably be better off if we were to call fat gain "lipohypertrophy," fat loss "lipoatrophy," and then talk about problems with sugar and fat separately, rather than try to make them all into the one thing.

Nelson Vergel: It is not one thing; they are different syndromes that may happen together or separately.

Dr. Donald Kotler: Right.

Nelson Vergel: You're saying that lipoatrophy -- which is fat loss under the skin in the extremities (e.g., legs), body and face -- is actually not occurring as much in the United States, because we're not using AZT or d4T. But how about fat gain? Is fat gain occurring as much as we used to see it in the '90s, for instance?

Dr. Donald Kotler: Fat gain is, I believe, as common now as it's ever been. I don't think that that's really changed. About one-third of the patients complain of fat gain.

Bonnie Goldman: Are most of the complaints about belly fat? Or are people still seeing fat gain in their neck? Is there one that's more likely?

Dr. Donald Kotler: Belly fat is much more likely. Belly fat is, like I said, a problem in about a third of the patients. Of the people who gain fat behind the neck, probably somewhere between 5 and 10 percent will have a big growth.

Interestingly enough, there are some obese people, who are not HIV infected and not otherwise ill, who actually have small humps. The humps are called buffalo humps, but in HIV, they seem to grow much, much larger.

Nelson Vergel: Dr. Kotler, how does somebody know if they're gaining more weight than normal because they're eating more, or whether it's something related to HIV, or HIV medications?

Some people complain about increased appetite once they start HIV medications. Is the fat gain related to their caloric intake (i.e., how much food people are actually taking in)? Or is there something else -- maybe the fact that their immune system may be getting better?

Dr. Donald Kotler: You know how much weight you can lose when you're sick and then, after you're done being sick, how much weight you can gain, and how fast you can gain weight just when you become healthy?

It turns out that when people start their antivirals, especially when the T cells are down around 200, they are sick. They may not know it. They may not realize it. But they're sick.

If you think about it, antivirals are not appetite stimulants. They're not anabolic agents. So how come people are gaining so much weight? I think the answer to that is that they were sick and had lost weight; so people were thinner than they would normally be and when they take antivirals, it brings them back to a normal weight -- "normal" in the United States is at risk of obesity.

Nelson Vergel: So it is actually better for somebody to start treatment when they're healthier, if they want to avoid any body changes? Is that it?

Dr. Donald Kotler: The literature would say yes. People have looked from the very start as to what makes people lose weight, what makes people gain weight. It turns out that it's a lot of things. Things related to the patient -- for example, family history.

Before you got HIV, if you were 280 pounds, you're probably a lot more likely, when all is said and done, to complain of a big belly than to complain of skinny legs. Whereas if you started out 5'10", 130 pounds, you are probably much more likely to complain that your face looks bad or the veins in your legs are really prominent, than complain of having a big belly.

If everybody in your family is obese, you're probably more likely to have problems on therapy by being obese rather than being skinny.

Nelson Vergel: Have you seen any differences whatsoever with respect to what people start with? Different types of HIV treatments? Are there any data out there that show whether people who start, for instance, on Atripla [efavirenz/tenofovir/FTC] versus Kaletra [lopinavir/ritonavir] or Truvada [tenofovir/FTC] have any differences in body changes?

Dr. Donald Kotler: There are not a lot of data on that, I must say. I don't know that I answered the last question well enough. But, there are many factors that will affect what happens to the patient. These factors can be related to the virus, they can be related to the HIV medication or they can be related to the patient himself, or herself.

For example, family history is related to the patient. Taking a drug like d4T is related to, obviously, the drug. Many people have several of these predisposing factors.

Nelson Vergel: Lipodystrophy (or what we used to call lipodystrophy and are now calling metabolic disorders) also includes increases in triglycerides and cholesterol, especially the bad cholesterol, and decreases in HDL [high-density lipoprotein], the good cholesterol.

Are people with increases in cholesterol and triglycerides more prone to having belly fat increases? Have you seen anything on that subject?

Dr. Donald Kotler: In general, people with a lot of belly fat tend to have increased levels of cholesterol. But there are some medications that, even if given to people who are very thin, will cause cholesterol levels to go up. And there are certain genetic tendencies in people that may make their cholesterol go up high, often when they take antivirals, whether or not they are obese. So you don't have everything or nothing. You can have a big belly and high cholesterol, but you don't necessarily have to have a big belly to have high cholesterol.

Bonnie Goldman: Dr. Kotler, can you specify which medications you are referring to in terms of raising the cholesterol, or raising the fats in the blood?

Dr. Donald Kotler: The one that does it more than any other is ritonavir [Norvir]. It turns out that it depends on how much you take. If you take, for example, the drug Reyataz [atazanavir], you only take one Norvir. If you're taking Kaletra, on the other hand, you take two Norvir. If you take the drug tipranavir [Aptivus], I believe you end up taking four Norvir in a day -- because that's what you need in order to get good drug levels to keep the virus under control. But it turns out that the more Norvir you take, the higher the fat levels are in the blood.

Bonnie Goldman: In Kaletra, you're taking the Norvir within the one pill that you're taking.

Dr. Donald Kotler: Right. You don't take a Norvir tablet. It's inside the Kaletra tablet.

Bonnie Goldman: Many people aren't aware that when they're taking Kaletra, they're also taking Norvir.

Nelson Vergel: Dr. Kotler, another assumption people make -- and I think even some clinicians out there -- is that if you treat high cholesterol with a cholesterol-lowering drug, or anything else that treats it, you will tend to decrease belly fat. Is that a right assumption? Are there any data to substantiate that?

Dr. Donald Kotler: No. It's the other way around. If you have a big belly and high cholesterol, and you make the belly small, the cholesterol will go down.

But if you have a big belly and high cholesterol, and you take a drug to lower the cholesterol, it may not do anything to your belly.

Nelson Vergel: Are there any treatments right now for the belly fat gain?

Dr. Donald Kotler: No. There are no treatments that are approved by the FDA [U.S. Food and Drug Administration]. Obviously, losing weight does something, although many people will say it doesn't do nearly as much as they want it to. You try to lose weight to lose your belly, but then you lose your butt, or your face looks worse and your belly doesn't change all that much.

Nelson Vergel: How about exercise?

Dr. Donald Kotler: Some people do that. Exercise will do it. The exercise that tends to do it is more resistance training exercise (i.e., lifting) than aerobics, surprisingly enough.

Nelson Vergel: Some people are actually afraid of aerobics because of fat loss.

Dr. Donald Kotler: Exactly. There are other people who have shown that some of the antidiabetic medicines, such as Glucophage [metformin], have been shown to decrease belly size.

There were several studies that looked at the drug growth hormone. Growth hormone did significantly lower belly size, but the FDA didn't approve it, likely because they were not happy with the side effect profile. They thought it was too toxic a drug.

Now, a month and a half ago, there was a meeting in London, the 10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. At that meeting, two other treatments were talked about. One was a drug called IGF-1 [insulin-like growth factor 1], or IGF-1 combined to a binding protein.

It's what growth hormone causes to happen. But here, rather than using growth hormone, they use the IGF-1. And rather than this worsening toxicity, worsening blood sugar, it actually made it better. It also caused an anabolic effect: lean mass went up and the amount of fat in the trunk went down. But it didn't really lower it as much as had been seen before with growth hormone. But it was a little, tiny study, just to show that it could work.

In addition, there's a drug called tesamorelin, which [acts as a] growth hormone-releasing factor. So when you give tesamorelin, you get a growth hormone-like effect and that also causes belly fat to go down. It doesn't cause glucose to get worse, like growth hormone does.

At this same meeting in London, Julian Falutz from Montréal looked at the two studies of this drug, tesamorelin, to see if it mattered what kind of antivirals are used.2 Does it matter if someone is taking protease inhibitors or the non-nucleosides? Does it matter whether someone is taking Kaletra or Sustiva [efavirenz, Stocrin]? It turns out that it doesn't matter. The drug tesamorelin will cause body fat to decrease. It will cause belly fat to decrease, no matter what your drug is.

Nelson Vergel: That drug is not approved yet?

Dr. Donald Kotler: The drug is not approved yet. But there have been several studies that have shown its benefit -- three, actually. I believe the FDA is looking at it now or, if not now, very, very soon. [Click here for more on tesamorelin.]

Nelson Vergel: If you were an HIV-positive patient, right now, in 2009, and you had problems with belly fat, what would you do? Just diet and exercise? Is that all we have?

Dr. Donald Kotler: Right now diet and exercise are the best hope. I would not treat with an antidiabetic medicine in the absence of diabetes.

Nelson Vergel: So you're not sure whether, for instance, Glucophage, which is an antidiabetic drug, would do anything for somebody who is experiencing belly fat gain.

Dr. Donald Kotler: Let's say you have to wear a size 40 pants, or keep your pants so low that your belly hangs over in a not very nice looking way, and you start taking Glucophage. Your waist will probably go from 40 to 39. You wouldn't go down to a 33, or a 32, or even a 34. The effect of Glucophage is really tiny.

When it was used at high doses, the effect of growth hormone was more like two or three inches. You'd go down to a 37 or a 36 waist. But it was real toxic and caused a lot of problems. Drugs like tesamorelin cause your waistline to decrease only an inch or so.

Nelson Vergel: The unfortunate thing, in my point of view, is that we haven't really seen combinations of therapy. For instance, researchers have not looked at exercise plus either the growth hormone-releasing factor or Glucophage. As an activist, I think I'm also a little frustrated that there are no real guidelines on the nutritional aspects of this problem. Like you said, nutrition and dieting. Where do we send people when they want information about what to eat? Do you recommend just a Mediterranean diet? Anything specific?

Dr. Donald Kotler: A Mediterranean diet would work well. People tend to do better with low-carbohydrate diets, as opposed to low-fat diets whether they are HIV positive or HIV negative. For people who don't know what a Mediterranean diet is, it is olive oil, nuts, very low in highly saturated fats, more fish and less meat. [Click here for more details on what a Mediterranean diet is.] But there has been very little data published on it, in terms of its effects in HIV.

Nelson Vergel: That brings me to the next question. If you had all the money in the world, what would be your main research project, when it comes to the area of body shape disorders in HIV?

I'm interested in your view since you both see patients and do research -- which is a good thing since many researchers don't actually see patients.

Dr. Donald Kotler: That's an easy question. If I had all the money in the world, I would study everything. But if I could only do one thing, what would I do? It would be a comprehensive program in which I wouldn't be looking for one treatment, but rather, I would use the combination.

It would be diet and it would be exercise and it would be medication. Our laboratory presented a study at the lipodystrophy meeting in London, in which we compared diet and exercise to diet and exercise plus the drug rosiglitazone [Avandia], or simply rosiglitazone alone. Rosiglitazone is an insulin-sensitizing agent; it's an antidiabetic agent.

The question we asked is: If we treat an HIV-positive person with big-belly lipodystrophy and an HIV-negative person who has a big-belly metabolic syndrome the same, would they respond the same?

If I got somebody who has HIV to lose 15 pounds and get into good shape, would his or her insulin resistance change the same as someone who is HIV negative?

Although we didn't have enough people in the study to be able to be absolutely confident of the results, it seemed that the two groups responded pretty much the same.

The average weight loss we got was about 15 pounds. The changes in an HIV-positive and in an HIV-negative person were really pretty much the same not only in the belly, but also in things like cholesterol and the special types of good cholesterol and bad cholesterol.

It looked like HIV didn't really influence it very much. So in the absence of any other information, I would treat an HIV-positive person the same as I would treat an HIV-negative person with metabolic syndrome. The best treatment is to treat it all -- not looking for one magic pill, but instead getting people to eat less, getting people to eat smarter and getting people to exercise more. If there is high cholesterol, bring it down. If the triglycerides and other types of fat are high, bring them down.

If the usual medicines don't work, well, then you try other things, like fish oil (omega-3 fatty acid) or niacin. There are a number of these new medicines that have been tried in HIV. They seem to work about as well in HIV as in non-HIV; it's not so different.

So I think that the optimal way to do it is a whole integrated program.

Bonnie Goldman: But don't you think that many patients around the country don't have a physician that they could turn to who may have this kind of very understanding point of view?

Dr. Donald Kotler: Maybe not a lot of private doctors, but there are a lot of clinics that are putting together metabolic clinics that are putting together expertise to look at having a cardiologist or an endocrinologist treating diabetes go into the HIV clinics to treat people.

You're right. It's not really fully integrated. But I think that would be the best.

Nelson Vergel: As an activist, I think the community also has to take an active role in advocating for things like this. In Houston, Texas, we have a non-profit where we provide exercise and dieticians looking at people's diets and trainers. Yet in the past five years, we haven't been able to duplicate these kinds of programs anywhere else because of money. Money and funding are really tight lately, especially in HIV. People sometimes don't even have the money to get the treatments, the HIV medications, which are basic. So it's a battle.

My next question -- which is really relating to this -- is: How do we get insurance companies or Medicare/Medicaid -- other systems that pay for medication -- how do we get them to accept that body changes in HIV are not a cosmetic issue, per se. It's something that not only affects people's self-esteem, anxiety and depression, and quality of life, but it may actually be something that also affects their survival, eventually.

That's where we have the most challenge right now. How do we shift from perceiving this as a cosmetic issue -- shifting third-party payers, insurance companies, to see it as a clinical problem?

Dr. Donald Kotler: It's not really a medical question. It's a question for activists. I think that the answer is activism. My suggestion would be to push it as a comprehensive care program, rather than a reimbursement for drug X. Because in fact some of the treatments are so costly that I don't know that I would be happy paying for the treatment in somebody who is not watching their diet or someone who would not consider doing exercise. Or even -- which is what's happened before and which is what I think limited it before -- you don't necessarily even look at the results of what you're doing; that it's really considered more of an entitlement to get the prescription, as opposed to having somebody measure you, work out your risk, give you some treatment and follow up. If you're not responding the way you should, look to find out why. Sometimes the medicine is not even being taken.

I think it's important to accept the fact that there's not a magic bullet, but there are a lot of things that you can do to help yourself. I think that the activists should really push on that.

Nelson Vergel: That's my main goal. I just wanted to summarize it, because some people may be so concerned about this discussion, and they're considering going on HIV medications for the first time.

The fact is that we're not experiencing as many problems metabolically right now, compared to 10 years ago. Is that a fair statement, in your point of view? Should people be really concerned before they start treatment?

Dr. Donald Kotler: The one thing that doesn't seem to have changed is that if people gain weight, they may get a big belly.

On the other hand, the diabetes that used to be seen, especially with Crixivan [indinavir], we don't see much of that anymore. There may be more diabetes that comes with Zerit or AZT, but for people taking the newer medicines, we don't tend to see that nearly as much.

The lipoatrophy -- the skinny face, the skinny butt and the really skinny legs -- if we see somebody now who has that, it's somebody who has been treated with HIV medications for a long time, and has had that for years.

With the new HIV medicines, it doesn't tend to happen that much anymore. The high triglycerides and high cholesterol: We still see some of it, although much of it occurs in people who are genetically predisposed to it.

The new medicines, like the integrase inhibitor Isentress [raltegravir, MK-0518], the CCR5 antagonist Selzentry [maraviroc, Celsentri] or the entry inhibitor Fuzeon [enfuvirtide, T-20], don't seem to cause any of these problems.

I think that people now are a lot less likely to develop these changes than they were in the past. It may be that if people are really careful about trying to prevent weight gain and eating very healthily at the time they start their antivirals, they may be much less likely to get it. On the other hand, if somebody weighed 280 before any of this happened and you make them healthy again, they are, as likely as not, going to go back to a weight of 280.

Nelson Vergel: Are some of these changes related to aging, or are they really accelerated aging by HIV and HIV medications?

Doctors are also saying to patients, "Well, don't complain. You really are healthy. It's just that you are getting older, too."

Dr. Donald Kotler: They are steady changes. But if you look at HIV-negative people, even though the changes are pretty continuous, when do people start really seeing the belly fat? And when do men start losing their butt, even if they're not HIV infected? It seems to be somewhere between ages 45 to 50. At that point, jeans fit differently. They are no longer tight in the thighs and loose in the waist; it's the other way around.

Nelson Vergel: There are also some hormonal changes, too, right?

Dr. Donald Kotler: Right. People's own growth hormones go down. People's own testosterone levels go down.

Nelson Vergel: Even thyroid. We're seeing some reports on thyroid dysfunction in some patients, too, right?

Dr. Donald Kotler: That's kind of an immune reconstitution problem, though. You'll get laboratory abnormalities. It really causes your thyroid to get so bad that you need hormone replacement.

Nelson Vergel: So it is good for patients who are experiencing some of these changes to at least get some of their hormones checked and talk to their doctors about it, right?

Dr. Donald Kotler: Absolutely. Women tend to have more problems with thyroid than men, so it's especially important in a woman, because she might develop a thyroid problem totally independent of HIV. Not everything that happens to people who are HIV positive is really HIV related.

Nelson Vergel: Dr. Kotler, one last question from my side. We're seeing some reports on decreases in bone density. Is that something that you see in your practice? I'm not even talking about research. I'm talking about your practice. You see a lot of patients in New York. You've been around since the '80s. I think you're probably one of the leaders in metabolic disorders.

In your practice, are you starting to see any bone-related fractures or any bone-related problems?

Dr. Donald Kotler: Yes, I've been seeing this for a long time. In fact, the bones that I've seen break most commonly, being in the middle of a city, are bones in the feet in people who run on treadmills. I don't see a whole lot of broken hips, broken ribs or crushed vertebrae. But I've seen people break bones in their feet, simply by the pounding.

At the meeting in London, there were a couple of interesting talks about bone. It's known that thin bones, brittle bones, are very common. Whereas most people blame antivirals, you can also see it in HIV-positive people who are untreated. So HIV-positive, treatment-naive people also may have thinned, decalcified bones. If that's the case, well, then it can't just be due to drugs!

There are two possibilities. Actually, the one possibility that many researchers are leaning towards is that when you're sick, you have inflammation. Inflammation tends to cause bone to break down.

Just like somebody who has chronic bronchitis from cigarette smoking and on that basis gets brittle bones, somebody can have a chronic infection with HIV and get brittle bones. It was felt that it was just the inflammation.

However, a group from Ireland exposed growing bone cells to HIV in serum -- either a low viral load or a high viral load or a negative viral load -- and showed that, when you exposed the cells to HIV, the bone cells tended to turn into fat cells. Bone cells and fat cells are related. So there may be something about HIV itself that tends to shut off the calcium being laid down in the bone. That was brand new information that hadn't been seen before.

There was another study, though, and this was really very hard to understand. It was related to the SMART study. You remember the SMART study?3 In that study, patients either stayed on therapy or, when their T cells went up, they stopped therapy, and then when their T cells went down, they started treatment again. It was a big study of a couple thousand people. [Click here to read more about the SMART study and treatment interruptions.]

Two hundred seventy-five of the people in the study actually had bone density studies done, either when they were on continuous therapy, or starting and stopping.

In fact, in that study, the people who stayed on therapy tended to have more bone problems than those who started and stopped. The author said that is not a reason to start and stop. So don't take that as a reason. But the people who were on therapy and didn't stop were more likely to have fractures and, when they were followed over, I believe, two years, they were more likely to lose calcium in their bones than the people who did start and stop.

That was a surprise finding, as almost everything out of the SMART study is. Nobody's really sure what to make of it, other than, as we move forward, we probably should be concentrating on bone density and making sure that we don't allow our patients to get to the point where they are likely to have fractures.

Nelson Vergel: That's definitely a problem I'm seeing. Very few doctors are prescribing bone scans, DXA [dual energy X-ray absorptiometry] scans, before therapy or once every few years to follow up on patients even if they don't think it's a problem; it's just that it's really not part of standard of care. That's another activist issue.

Dr. Donald Kotler: The activist issue is reimbursement.

Nelson Vergel: Those who stayed on continuous therapy in the SMART study also had fewer problems with heart attacks and cardiovascular disease, right?

Dr. Donald Kotler: Right ... as well as other endpoints. The people who started and stopped are more likely to have problems with liver disease and are more likely to have problems with tumors. Starting and stopping has turned out not to be healthy.

Nelson Vergel: Any other questions, Bonnie? I think Dr. Kotler has been extremely helpful in clarifying some of the questions the community has.

Bonnie Goldman: If you have bone density issues, is it related to fat accumulation or fat wasting? Or are they all kind of the same phenomena?

Dr. Donald Kotler: Sort of, because they tend to be found in the same people. But no, I don't know how they are necessarily related in terms of the cause.

Bonnie Goldman: It sounds like there are hints of a lack of calcium in patients. Would this mean that it's a good idea to take calcium supplements to prevent bone density loss?

Dr. Donald Kotler: I don't know. I don't know if taking calcium supplements prevents it. That's the problem.

Nelson Vergel: Or exercise.

Dr. Donald Kotler: You should avoid vitamin deficiency. You should avoid eating too little calcium. That's mainly a problem in people who have trouble with milk and dairy. If you're lactose intolerant, you tend to eat less calcium than if you are not lactose intolerant.

Somebody who is at risk for bone loss should make sure they are taking enough calcium in their diet, should make sure there's at least enough vitamin D in their diet. I don't know, though, that just by taking an extra two vitamins everything will be cool. I just don't know that. I think that you would be better off having your bone density checked.

Certainly, if your bone density is low and you take the regular bone density medicines, like the kind that you see on TV, they do work.

I'm not sure how well vitamin D and calcium work. But the kinds of drugs, what are called bisphosphonates, that you either take every day, every week or every month, they do cause bone density to rise.

Bonnie Goldman: Do you see a lot of people having metabolic complication myths? They think it's due to all the protease inhibitors, or they think it's due to all antiretrovirals. Are there myths that we need broken?

Dr. Donald Kotler: I don't know. Patients tend, if they believe the doctor, to believe what the doctor tells them. So if there's a myth, it's probably the myth of the doctor. This whole idea that protease inhibitors caused everything didn't come from the patients. It came from the doctors. We had it wrong. We tend to have it wrong a lot, unfortunately.

Bonnie Goldman: I think that's one of the reasons that these kinds of complications -- bone, metabolic complications and body shape changes -- are so difficult. Because it's an ongoing understanding. And we don't know that much about this.

Dr. Donald Kotler: There's another part of it, though. It's that we're looking so hard at T cells, or viral load, that we just tend to forget about the rest. We're working so hard to make sure that people don't get cytomegalovirus (CMV), or toxoplasmosis, and die. When they get better and they're not going to die of the AIDS things, we can either say that's fine or ask what else would it be. As HIV docs we're not built to be worried about people's prostates or breast self-exams. We were aiming towards fighting pneumocystis pneumonia [PCP], CMV and all the rest. So we have had to retrain ourselves to be primary care physicians, to look at things that would happen to somebody who doesn't have a killer disease.

What happens to people without a killer disease? You either get cancer or heart disease. Or you develop Alzheimer's disease, or bad kidney disease, or all the other stuff. We're just coming around as doctors to realize that. Patients also have to come around.

Probably the best example of where patients and doctors have been caught short has to do with cigarette smoking. I knew it. If I had a patient who was dying of AIDS in 1985, I didn't bother much about them smoking cigarettes. What for? Now, it turns out that lung cancer is really common in HIV, and has nothing to do with HIV, it seems, and has everything to do with cigarette smoking.

So only lately have doctors like myself said, "Look, you're not going to die of AIDS. Why would you go through all that and then allow yourself to die of lung cancer? How could you be so crazy?" We're just getting around to that now.

Bonnie Goldman: You need to have a historic point of view to understand this whole issue, and how we came to the point where we're now dealing with this.

Dr. Donald Kotler: There's nobody to blame, because it's success. But if we want real success, it's not only not allowing somebody to die of AIDS, it's not allowing anybody to die before their time of anything. Drug overdose, as well.

Bonnie Goldman: And also dealing with quality-of-life issues -- you may live a long life, but you might have this belly that embarrasses you.

Nelson Vergel: Or facial wasting, or fatigue, or many other issues. One more question that I just thought of related to this talk about HIV doctors training themselves to be primary care physicians and treating people that are aging with HIV and who are showing up with some of these metabolic problems: Are there any Web sites, any groups, where guidelines are posted for doctors when it comes to metabolic disorders? One place, one document? Anything that doctors who are starting to treat HIV nowadays can go to to train themselves?

Dr. Donald Kotler: If you google "HIV metabolic guidelines," there have been several from the International Association of Physicians in AIDS Care, and from the International AIDS Society-USA. I believe that the Europeans also have one. There are some guidelines that are written. The early guidelines were not great. They would say, "In the absence of information, you probably should treat diabetes in HIV like you treat diabetes in non-HIV." For high cholesterol, or high triglycerides, as well, you should consider the medications. After that, you should treat just like you would treat anybody else.

I think the major point is that you don't ignore something that's bad. In the past, we ignored cigarette smoking, because we were worried that people were going to die of CMV.

Now we shouldn't ignore cigarette smoking. We shouldn't ignore high cholesterol, and we shouldn't ignore diabetes. We shouldn't ignore excess weight gain. We shouldn't ignore any of it.

Bonnie Goldman: So, success has allowed us to focus on these other details.

Dr. Donald Kotler: Yes, and those who are successful have more work to do.

Nelson Vergel: I also remind patients that HIV medications may have some side effects, but the worst side effect is leaving HIV untreated. I always say that, because sometimes we lose perspective and forget that these medications have kept a lot of us alive for 20-plus years. Sometimes the new guys and girls that are coming through with treatment are so afraid. I remind them that leaving HIV untreated can cause more problems than any side effects they may have in the future that can be treated by a good doctor.

Dr. Donald Kotler: I was in clinic today and saw a 24-year-old girl with a CD4 of 5, who had herpes around the rectum and around the vagina, who was being treated for MAC [Mycobacterium avium complex] infection in the liver, who has a huge liver, and who also probably has CMV. She had lost 70 pounds. She doesn't leave the house. She feels miserable. There's no reason for it.

Nelson Vergel: She got to a good doctor, though.

Dr. Donald Kotler: She's at a good clinic.

Nelson Vergel: A good clinic, that's lifesaving. Anything else, Bonnie? Dr. Kotler has been great.

Bonnie Goldman: I think this is really great, and hopefully it explains some of the phenomena that people have been experiencing. Maybe it will motivate a lot of people to go on a diet, do some exercise and take charge of their health in that way, while waiting for other treatments or other understanding of metabolic complications.

Nelson Vergel: Hopefully, we'll bother Dr. Kotler in the future to give us more details about any progress in this field, too. So, thank you.

Bonnie Goldman: Thank you so much for taking the time to talk with us. Thank you, Nelson, for joining us and for leading the conversation. I really appreciate that.

Nelson Vergel: Thanks a lot for having us! We'll talk to each other soon, I hope.

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References
Lazzaretti R, Pinto-Ribeiro J, Kummer R, Polanczyk C, Sprinz E. Dietary intervention when starting HAART prevents the increase in lipids independently of drug regimen: a randomized trial. In: Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract WEAB303.
Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. December 6, 2007;357(23):2359-2370.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. November 30, 2006;355(22):2283-2296.
For more information on facial wasting, check out our lipoatrophy resource center.

Click here to read Mark King's latest blog about treatment for facial wasting.




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LA LIPODISTROFIA Y EL VIH

LA LIPODISTROFIA Y EL VIH
¿DÓNDE ESTAMOS LUEGO DE DIEZ AÑOS?Por Nelson Vergel, Director del Program for Wellness Restoration,powerusa.org


La primera vez que apareció un informe acerca de la Lipodistrofia en una Conferencia sobre el VIH fue hace diez años. La excitación y la esperanza de una vida más larga que vino aparejada con la aparición de los protocolos de Terapia Antirretroviral Altamente Activa (Highly Active Antiretroviral Therapy - HAART -) fueron atemperadas con reportes de jorobas, panzas y enflaquecimiento facial. Una década ya ha transcurrido y muchas de las preguntas y conceptos erróneos acerca de la lipodistrofia asociada con el VIH persisten aún hoy en día, con tan solo un puñado de tratamientos alternativos disponibles. Mucha gente que padece de lipodistrofia, frustrada y cansada de esperar respuestas de la comunidad médica, se ha volcado al Internet para tratar de encontrar consejos, tratamiento y ayuda, con la esperanza de revertir algunos de los devastadores efectos de este síndrome que es causa de gran estigma.
La lipodistrofia es una condición que implica una redistribución anormal de tejido adiposo. Dicha redistribución puede conducir ya sea a una lipohiperatrofia (acumulación de tejido adiposo en áreas específicas del cuerpo, tales como el cuello, la barriga, la parte superior del torso y las mamas) o bien a una lipoatrofia (pérdida de tejido adiposo en la cara, glúteos, brazos y piernas). Un encuesta que se realizó a través del Internet con 695 individuos (predominantemente varones de raza blanca, mayores de cuarenta años de edad, que han estado viviendo con el VIH por lo menos por diez años y que han mantenido su terapia HAART por lo menos por diez años) descubrió que un 20% ha considerado el suicidio por cambios corporales asociados con la lipodistrofia. Alrededor del 90% de los encuestados opinaron que los medicamentos que están tomando para combatir el VIH son la causa de la lipodistrofia y un 20% de los encuestados dijeron haber abandonado su medicación por completo debido a este problema. Aparte, más del 60% de los encuestados afirmaron haber sido rechazados por parejas potenciales para sexo debido a este síndrome. Un número similar de encuestados indicó que inclusive habían dejado de mirarse al espejo porque la imagen que veían les causaba una sensación de invalidez. Casi todos los individuos encuestados indicaron haber tratado de minimizar los efectos de la lipodistrofia a través de dieta y ejercicio físico o utilizando procedimientos de reconstrucción facial de un costo sumamente elevado, suplementos y hormonas (todos éstos, tratamientos que no son típicamente cubiertos por los seguros médicos o por programas de asistencia médica).
La Lipoatrofia y los Medicamentos contra el VIH.
En 1999 la droga contra el VIH denominada Zerit fue asociada con el desarrollo de lipoatrofia relacionada con la pérdida de tejido adiposo bajo la piel1. Desde entonces, un número de estudios ha concluido que el Zerit puede afectar la forma en que la mitocondria (que es la fábrica de energía de la célula) de nuestras células trabaja y se multiplica. Posteriormente, otros estudios concluyeron que el AZT ocasionaba un problema similar, aunque a una menor tasa que el Zerit. Medicamentos clasificados como Inhibidores de la Transcriptasa Reversa Análogos de los Nucleósidos o Nucleótidos (NRTIs) tales como el Zerit o el AZT impiden que el VIH altere el material genético de los Linfocitos T saludables, y a través de dicho proceso, detienen la reproducción de nuevas células virales. Adicionalmente, los NRTIs afectan también la mitocondria de las células adiposas que se encuentran bajo la piel, impidiendo que se multipliquen y causando su muerte. Por otra parte, individuos que han estado bajo la terapia combinada de Zerit y Videx (otro NRTI) han mostrado una incidencia más aguda de lipoatrofia que aquellos que han estado tomando solamente Zerit. La combinación de Zerit y Videx no es aconsejada por grupos consejeros. Pareciera ser que el Zerit y el AZT empeoran la acumulación de tejido adiposo cuando se los utilizan combinados con Inhibidores de la Proteasa o No-Nucleótidos Análogos (NNRTIs) tales como Sustiva, lo que ha llevado a los investigadores médicos a sospechar que sus efectos negativos pueden funcionar en forma combinada. Sin embargo, la ingesta de Sustiva con Viread (Tenofovir) y Epivir (3TC) parece causar menos lipoatrofia. Debido al alto riesgo de producir lipoatrofia y neuropatías, la comisión de guías directivas del Departamento de Salud y Servicios Humanos de los Estados Unidos eliminó al Zerit de la lista de medicamentos recomendados como primera línea de ataque para pacientes que han sido recientemente incorporados a la HAART.
El Viread (Tenofovir) y el Ziagen (Abacavir), que son dos drogas pertenecientes al mismo grupo NRTIs que el Zerit y el AZT, parecen no mostrar una correlación tan severa con el desarrollo de la lipoatrofia. Algunas personas inclusive han reportado una lenta reversión de la pérdida de tejido adiposo luego de haber dejado de tomar Zerit o AZT y cambiado ya sea a Ziagen o Viread. Sin embargo, la mayoría de los pacientes han reportado que, a pesar de haber transcurrido un número de años desde que abandonaran la terapia de Zerit o AZT, no experimentaron ningún tipo de re-acumulación de tejido adiposo en el rostro. Es importante destacar que una nueva y paradójica información obtenida de un reciente estudio realizado por el AIDS Clinical Trials Group2 ha señalado que una pérdida de tejido adiposo subcutáneo (pérdida del tejido adiposo más cercano a la superficie de la piel) del 20% ocurrió en un pequeño porcentaje de pacientes que habían recién entrado en la terapia HAART por primera vez utilizando una combinación de Sustiva, Viread y Epivir. Se va a necesitar un mayor número de estudios para determinar por qué la lipodistrofia todavía es un fenómeno que ocurre en algunos pacientes donde existe una ausencia de Zerit o AZT.
Las ventas de Zerit y de AZT en los países industrializados han disminuido considerablemente recientemente debido al efecto que estas drogas tienen sobre la lipodistrofia. Desafortunadamente, estas dos drogas figuran entre los principales medicamentos contra el VIH utilizados en los países en vía de desarrollo, lo cual implica que millones de personas en países más pobres van a tener que continuar padeciendo transformaciones corporales.

Opciones Para el Tratamiento de la Lipodistrofia.
Desde hace algunos años a la fecha, muchos varones han dependido de un anabólico esteroide inyectable genérico denominado decanoato de nandrolona (su denominación comercial es Deca Durabolín), a fin de tratar de balancear sus cuerpos, añadiendo masa muscular a las extremidades y glúteos que estaban perdiendo volumen, afectados por lipodistrofia. A pesar que los Laboratorios Watson dejaron de producir la nandrolona en Marzo de 2007, es posible adquirirla (expendio bajo receta) a través de farmacias mayoristas por un costo relativamente bajo3.
Existe un suplemento denominado Uridine (Nucleomaxx), elaborado a partir de la caña de azúcar y accesible a través de un distribuidor alemán4. Este suplemento puede ayudar a disminuir la lipodistrofia en pacientes que están tomando Zerit, pero también puede ocasionar acumulación de depósitos de grasas en la zona abdominal e incrementar el nivel de triglicéridos. Debido a estos efectos colaterales, su elevado costo y mal sabor, Uridine no ha tenido una amplia recepción. Sin embargo, para aquellos de deben tomar Zerit, Uridine puede ser una opción viable para prevenir o inclusive revertir lipodistrofia. Adicionalmente, para aquellos individuos que han dejado de tomar Zerit, la droga contra diabetes denominada Rosiglitazone (Avandia) ofrece muy buenos resultados para revertir los efectos de lipodistrofia. Existen, sin embargo, efectos colaterales, incluyendo el aumento de peso y triglicéridos elevados.
Desde el año 2002 han aparecido un par de procedimientos de reconstrucción temporal para tratar la lipodistrofia facial. Una de estas opciones es Sculptra (ácido poli láctico, cuyo nombre comercial anterior era New Fill), la cual implica una serie de sesiones múltiples de costo elevado , y requiere de retoques adicionales. Sculptra puede ser utilizada por aquellos individuos que han sido moderadamente afectados por lipodistrofia. Radiesse es otra opción aprobada por el FDA en los Estados Unidos. Radiesse requiere un mayor número de sesiones, y es más caro que Sculptra, requiriendo de 3 a 5 sesiones y retoques anuales. Algunos pacientes tratados por enflaquecimiento facial con este tipo de productos han experimentado efectos colaterales, tales como hematomas y granulomas tratables (nódulos que tienen la apariencia de espinillas endurecidas).
Existen algunos programas de asistencia para el paciente, disponibles tanto para Sculptra como para Radiesse5.
No existe ningún tipo de solución permanente para la lipoatrofia facial aprobada por el FDA de los Estados Unidos. Sin embargo, muchos individuos en este país utilizan unas inyecciones minúsculas de silicona (Silikon 1000), aplicadas por un especialista. El Silikon 1000 puede ser utilizado legalmente como una substancia genérica para el tratamiento de lipoatrofia facial. Las micro-inyecciones de Silikon 1000 pueden reconstruir lentamente los rostros de los pacientes, en unas cinco sesiones, espaciadas por un mes entre sesión y sesión. No existe ningún tipo de programa de asistencia para el paciente para esta opción, cuyo costo por sesión puede oscilar entre U$D 600.- y U$D 900.- Lamentablemente, también para el caso de Silikon 1000 se requieren múltiples sesiones. Hay que tener muy presente que hay tan solamente muy pocos profesionales en los Estados Unidos que están bien entrenados en la aplicación de este procedimiento.
Existe otro producto para la reconstrucción facial permanente, denominado Polimetil-metacrilato (PMMA). Este producto ha sido utilizado en Brasil durante ocho años y en Méjico durante tres con resultados relativamente positivos, aunque se va a necesitar más tiempo para determinar los efectos en el largo plazo de este procedimiento. Requiere generalmente de dos a cuatro sesiones, sin tener que incurrir en retoques anuales. Hemos visto en el corto plazo que para algunos pacientes el PMMA puede endurecerse y tomar forma grumosa, aunque muchos pacientes parecen muy satisfechos con los resultados. El Artefill es un producto con base PMMA, y tiene la aprobación del FDA en los Estados Unidos para propósitos cosméticos, pero no para el tratamiento de lipoatrofia relacionada con el VIH. Artefill es extremadamente caro en las cantidades necesarias para tratar lipoatrofia, por lo que pacientes seropositivos en los Estados Unidos van a Méjico o Brasil para tener acceso a dicho tratamiento, donde el costo puede oscilar de U$D 2.000,- a U$D 6.000,-. El PMMA es permanente (no se lo puede remover una vez inyectado).
BioAlcamid (poli alkilamida gel), es otra opción también permanente. Es una substancia inyectable que se encuentra disponible en los Estados Unidos (algunos pacientes viajan a Méjico o Brasil para tener acceso al tratamiento a un menor costo). Lamentablemente, BioAlcamid genera un “bolsillo” en la cara y en los glúteos, el cual es permeable para el acceso de bacterias, por lo que presenta un alto riesgo de infección. Como tal, aconsejamos extremado cuidado antes de decidir seguir esta opción.
No existe ninguna base de datos de largo plazo en lo referente a estos procedimientos experimentales para reconstrucción facial, por lo que los riesgos de inyectar una substancia extraña al organismo deben ser cuidadosamente considerados. Desafortunadamente, mucha gente siente que el costo emocional, sicológico y social que trae aparejado vivir con lipodistrofia es tan elevado, que para muchos se justifica tomar estos riesgos.

Opciones Experimentales para el Tratamiento de la Lipohiperatrofia.
A diferencia de la lipoatrofia, los investigadores médicos no han podido llegar a atribuir la lipohiperatrofia (acumulación de tejido adiposo en la barriga, parte posterior del cuello y mamas) a ningún medicamento o clase de droga en particular. En una ocasión se pensó que los inhibidores de la proteasa eran los principales causantes. Sin embargo, recientemente se ha descubierto que la acumulación de tejido adiposo en la zona abdominal puede estar relacionada con una respuesta inflamatoria del sistema inmunológico cuando baja el número de los linfocitos T CD4. Esto significa que aquellos que comienzan el tratamiento de terapia HAART con una menor base de linfocitos T CD4, se pueden encontrar con casos más pronunciados de lipodistrofia. Por otra parte, datos recientes han revelado que pacientes con un nivel de linfocitos T CD4 superior a 250 y que están comenzando la terapia HAART con inhibidores de la proteasa amplificados con la ayuda de Norvir más Viread y Epivir, no han experimentado incremento en el nivel de grasa visceral (tejido adiposo que rodea a los órganos internos). Es aún muy temprano para aventurarse a decir qué va a ocurrir con individuos que comienzan el régimen con niveles bajos de linfocitos T CD4. Algunos estudios han mostrado que aquellos que comienzan tomando inhibidores de la proteasa combinados con Zerit, AZT o Zerit y Videz, tienen una mayor tendencia a incrementar el volumen de grasa visceral y una joroba que aquellos que comenzaron los inhibidores de la proteasa con otras drogas. Es factible que las mismas drogas que están vinculadas con la lipoatrofia puedan también hacer que el incremento de la cantidad de tejido adiposo sea aún mayor, especialmente en pacientes que comienzan la terapia HAART con un bajo número de linfocitos T CD4.
Un concepto erróneo promovido por algunas compañías farmacéuticas y que encontró eco en algunos profesionales médicos es que los medicamentos para tratar el VIH no incrementan el nivel de colesterol y que los triglicéridos no causan incrementos en el tejido adiposo. Por el contrario, varios estudios han señalado que pacientes que toman medicamentos que son congeniales con los lípidos tales como Reyataz combinados con Viread también experimentan un incremento en la cantidad de tejido adiposo en la barriga luego de comenzar la terapia HAART.
Se le preguntó al doctor David Nolan (clínico e investigador en el Royal Perth Hospital de Western Australia y experto en el metabolismo de lípidos y VIH) por qué el tejido adiposo visceral no “desaparecía” luego de la introducción de Zerit y AZT (tal como ocurre con el tejido adiposo subcutáneo). El doctor Nolan tuvo la hipótesis que es factible que el tejido adiposo que rodea los órganos internos no sea igualmente susceptible a la toxicidad generada por el Zerit y el AZT que el tejido adiposo subcutáneo.
El incremento en el tejido adiposo puede ser correlacionado a la resistencia a la insulina. La resistencia a la insulina puede causar intolerancia a la glucosa, la cual ha sido asociada con incrementos en el tejido adiposo, incrementos en los triglicéridos, y el desarrollo de diabetes. La insulina es una hormona producida por el páncreas para controlar el nivel de azúcar-glucosa en sangre. Los medicamentos contra el VIH pueden bloquear o desacelerar el proceso por el cual la insulina convierte la glucosa en energía. En estudios de laboratorio, el Crixivan y dosis más elevadas de Norvir y Zerit han mostrado su capacidad para atrofiar la acción de la insulina tanto en el tejido adiposo como en el muscular. En este caso, el páncreas va a producir mayores cantidades de insulina a fin de tratar de compensar la disminución en la función. Se pueden presentar elevados niveles de insulina durante años antes de que se desarrolle diabetes del tipo 2. Un análisis de tolerancia a la glucosa puede indicar este problema fácilmente, pero raramente se lo utiliza en la práctica. Adicionalmente, algunos individuos pueden tener una predisposición genética a la resistencia a la insulina. Un tipo de vida sedentaria y una dieta rica en azúcares y grasas de origen animal puede contribuir en forma cumulativa a este problema. En cualquier caso, la resistencia a la insulina puede ser tan solamente una parte del misterio de la lipohiperatrofia. No existe un acuerdo generalizado entre los investigadores sobre si monitorear o no los niveles de insulina en pacientes seropositivos es un instrumento confiable para determinar la resistencia a la insulina y el incremento de tejido graso.
Una absorciometría de rayos X duales para cuerpo completo es el instrumento ideal para casos de lipodistrofia. Es un análisis de gran importancia que puede proveer información acerca de la composición corporal (masa grasa, masa muscular y densidad ósea). La baja densidad ósea ha sido asociada con el VIH en varios estudios. Tanto el Medicare como seguros médicos privados generalmente cubren este análisis, el cual es relativamente económico. En tanto que este análisis no puede diferenciar entre la grasa acumulada en la barriga o la subcutánea en el área abdominal, puede ser muy útil como punto de partida para evaluar cambios corporales y para justificar terapias reembolsables para grasas, músculo y masa ósea.

Intervenciones en el Tratamiento para casos de Lipohiperatrofia.
Algunos pacientes han cambiado de inhibidores de la proteasa a Viramune o a Sustiva para combatir incrementos en la grasa visceral, pero esto no ha mostrado producir diferencia alguna. Todavía no se sabe qué ocurre con la grasa del abdomen cuando un paciente cambia de Zerit o AZT a Viread o Ziagen mientras aún se encuentra tomando inhibidores de la proteasa o NNRTIs tales como Sustiva o Viramune.
La hormona de crecimiento humano Serostim es una droga inyectable que se aplica en forma diaria, y ha sido aprobada por el FDA para el tratamiento del síndrome de desgaste asociado con el VIH. Con un costo mensual aproximado de U$D 3.000,- es una opción muy cara para el tratamiento de la lipodistrofia. El Serostim ha demostrado buenos resultados en materia de disminución de grasa abdominal, pero presenta una serie de efectos colaterales, incluyendo dolores en las articulaciones, retención de agua, síndrome de túnel carpiano, y diabetes irreversible. La combinación de todos estos efectos con la carencia de información acerca de beneficios comprobables para la salud en el largo plazo ha hecho que el FDA no haya aprobado el Serostim para el tratamiento de acumulación de grasas relacionados con el VIH.
El Tesamorelin -TH9507, elaborado por Theratecnologies- es un precursor de la hormona de crecimiento, inyectable en forma diaria, que se encuentra en las últimas etapas para aprobación por el FDA. El Tesamorelin aparenta tener menos efectos colaterales que el Serostim, pero puede necesitar de un mayor lapso de tiempo para comenzar a mostrar sus beneficios en los pacientes. Lamentablemente, la grasa previamente incrementada regresa a sus niveles existentes previos a la utilización de tanto el Serostim como el Tesamorelin, una vez que se descontinúen cualquiera de ellos.
Un nuevo elemento que ha aparecido en la carrera para encontrar una solución para disminuir la acumulación de grasa visceral es Leptin. Leptin es una hormona producida por las células adiposas. Los investigadores han descubierto que los niveles de leptin en sangre son proporcionales al nivel de grasa corporal del individuo. El leptin trabaja en la parte del cerebro que controla el apetito y otras funciones básicas. Elevadas concentraciones de leptin generalmente traen aparejadas una disminución del apetito a la vez que estimulan al organismo para que queme grasas. El leptin no aparenta tener impacto negativo alguno en la tolerancia a la glucosa.
Actualmente, los médicos prefieren prescribir testosterona bajo la forma de gel, inyecciones y comprimidos subcutáneos. El gel de testosterona aplicado sobre la barriga puede reducir el tamaño de la cintura en varones seropositivos. Esta disminución de tamaño es usualmente el resultado de la disminución de tejido adiposo subcutáneo y no de la grasa visceral. En contraste, un pequeño estudio piloto realizado con Oxandrin (un esteroide anabólico de ingesta oral) ha mostrado resultados significativos en materia de reducción de grasa visceral. Incrementos en las lipoproteínas de baja densidad (el denominado “colesterol malo”) y reducciones en las lipoproteínas de alta densidad (el denominado “colesterol bueno”) se correlacionan con una pequeña disminución en el tejido adiposo subcutáneo. No existe ninguna información hasta el momento que conecte un anabólico muy popular, el decanoato de nandrolona, con reducciones en la grasa visceral.
Algunos individuos que han estado buscando elementos que ayuden a quemar las grasas han sido víctimas de las técnicas publicitarias que tratan de impulsar suplementos de hormona de crecimiento o distintos elementos que se publicitan como efectivos para eliminar grasas. Estos productos generalmente tienen un efecto insignificante en lo que respecta a la eliminación de grasas, pero elevan la presión arterial y los niveles de ansiedad, y son generalmente considerados como una estafa.
La Metformin (comercializada bajo la denominación Glucophage) es una droga genérica contra la diabetes que ha mostrado ayudar a mejorar la tolerancia a la glucosa y para disminuir la grasa visceral en la parte inferior. Sus efectos se pueden inclusive incrementar cuando se la combina con un programa de ejercicio físico. La Metformin mejora la sensibilidad a la insulina, los triglicéridos y la grasa hepática, pero puede causar diarrea y conducir a una pérdida de peso. Se han reportado incluso algunos casos de bajos niveles de azúcar en sangre y episodios de mareos asociados con esta droga.
En adición a todos los tratamientos anteriormente mencionados, los pacientes siempre pueden optar por otro tratamiento: liposucción. La liposucción asistida por ultrasonido puede ser utilizada para remover exitosamente el tejido adiposo acumulado con la forma de una joroba de búfalo en la parte posterior del cuello.
Algunos pacientes han reportado el incremento de tamaño en las glándulas salivares en los costados de la cara, un efecto comúnmente denominado “cara de ardilla”. A pesar de que existen muy pocos radiólogos que saben cómo utilizar este procedimiento en forma correcta, unas bajas dosis de radiación de electrones han producido resultados muy satisfactorios en el tratamiento para la reducción de tamaño de las glándulas salivares en la parótida. Lo que no se tiene claro todavía es si este fenómeno de incremento de tamaño en las glándulas salivares está relacionado con la lipodistrofia o si es causado por una reconstitución inmunológica.
Otra alternativa sobre la que no se han hecho muchos estudios todavía es dieta y ejercicio. Un estudio realizado en la Tufts University mostró una tendencia hacia una menor lipodistrofia para aquellos individuos que tenían una mayor ingesta de fibras solubles (frutas y vegetales) y que hacían ejercicios físicos en forma habitual. A pesar de ello, se necesitan estudios en mayor profundidad en lo relativo a la utilización de dietas de carbohidratos simples. Estas dietas han mostrado su habilidad para mejorar la resistencia a la insulina y la reducción de la grasa visceral en estudios no relacionados con el VIH. Un estudio observacional mostró que los pacientes seropositivos tienden a ingerir mayores cantidades de grasas saturadas. Un pequeño estudio piloto combinando ejercicios cardiovasculares y ejercicios de resistencia mostró una disminución en triglicéridos y grasa visceral. Sin embargo, el problema es la continuidad en este tipo de programas, la cual constituye el mayor reto para la mayoría de la gente. Los estudios relacionando los efectos de ejercicio con casos de VIH se encuentran todavía en su infancia.

Incrementos en los Lípidos: Las Lipoproteínas de Baja Densidad (LDL) y Los Triglicéridos.
Las anormalidades más comunes en pacientes seropositivos son cantidades elevadas de triglicéridos y de LDL, o colesterol “malo”, y bajos números en lo que respecta a Lipoproteínas de Alta Densidad (HDL), o colesterol “bueno”. Es muy posible que individuos seropositivos antes de que comiencen la terapia contra el VIH por primera vez, tengan niveles inferiores a los normales tanto para las lipoproteínas de alta y de baja densidad. Sin embargo, luego de que se comience la terapia con drogas contra el VIH, en algunos casos se ha visto un incremento en las lipoproteínas de alta y de baja densidad, así como también en los triglicéridos. Algunos estudios han señalado que el nivel de lípidos de baja densidad (LDL) se incrementa para alcanzar los niveles existentes antes de la seroconversión, en tanto que los niveles de lípidos de alta densidad (HDL) nunca retornan a los niveles normales. El incremento en triglicéridos es el cambio más fuertemente asociado en materia de lípidos causado por medicamentos contra el VIH tales como inhibidores de la proteasa, Zerit, AZT o Sustiva. Dentro de todos los inhibidores de la proteasa, Reyataz parece ser el que se correlaciona con el menor incremento de lípidos.
Muchos pacientes prefieren comenzar a tomar suplementos antes de comenzar a tomar medicamentos para bajar el nivel de lípidos en sangre. Los únicos suplementos que han mostrado resultados sólidos en estudios sobre lípidos son los ácidos grasos Omega-3 (aceites de pescado), así como también la niacina (también conocida como Niaspan). Los aceites de pescado pueden disminuir los triglicéridos, pero algunos pacientes encuentran que sus estómagos no lo toleran muy bien. La niacina es mejor que cualquier medicamento para disminuir lípidos en cuanto a sus efectos para incrementar el colesterol “bueno”. Puede causar rubor en la cara y una sensación de calor que dura alrededor de una media hora, pero la mayoría de la gente se acostumbra a estos efectos. Recientemente ha aparecido una versión de Niacina que no causa rubor en la cara, pero su efectividad es desconocida a la fecha.
No está claro si Raltegravir (Isentress) o si Maraviroc (Celsentry -un inhibidor de punto de entrada CCR5-) tienen efecto alguno sobre la composición corporal. Hasta el momento, aparentan tener una buena correlación con los lípidos cuando se los toma en forma conjunta con Viread o Epivir. Fuzeon (un inhibidor de punto de entrada inyectable) también aparenta ser compatible con lípidos, pero se lo utiliza frecuentemente en forma combinada con inhibidores de la proteasa que pueden causar incremento en los lípidos. Pareciera ser que existen algunos factores genéticos que hacen que algunos pacientes presenten una tendencia a tener niveles más elevados de triglicéridos y de lipoproteínas de baja densidad (colesterol “malo”).
Agentes reductores de lípidos tales como las estatinas (Lipitor, etc.) o fibratos (Tricor, etc.) pueden tener unos efectos fabulosos en algunos pacientes, pero aún cuando se los utilice, algunos pacientes nunca llegan a niveles “normales” en el panel de lípidos. Se utiliza habitualmente una combinación de niacina, baja ingesta de azúcares y grasas animales, ejercicio, suplementos de aceite de pescado o un incremento en la ingesta de pescados aceitosos de aguas frías (salmón, por ejemplo) y fibras solubles (frutas, vegetales y avena) para tratar los lípidos. Algunos individuos han tratado la combinación de estatinas y fibratos, pero dicha combinación puede conducir a un incremento en desórdenes musculares para algunos pacientes.

Conclusión.
Hemos aprendido mucho en los últimos diez años acerca de los cambios corporales que vienen aparejados con el VIH, pero quedan aún muchas preguntas sin contestar. Es de anhelar que aquellos que recién están siendo introducidos a las nuevas terapias HAART no tengan que sufrir los devastadores efectos colaterales que sus predecesores tuvieron que enfrentar en los últimos veinte años. Como pacientes, es nuestra responsabilidad educarnos en la mayor medida posible y aprender de otras fuentes e individuos acerca de nuevas opciones que vayan apareciendo y que puedan hacer posible algún día el llevar una vida plena sin ninguno de los cambios corporales ni tampoco ninguno de los efectos colaterales que vienen asociados con el VIH.

Para mayor información, por favor visite el sitio: www.facialwasting.org, o si desea subscribirse al mayor grupo de discusión en el Internet acerca de temas de salud vinculados con el VIH, simplemente envíe un email en blanco a pozhealth-subscribe@yahoogroups.com.

1 A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. AIDS. 1999 Sep 10; 13(13):1659-67.
2 Metabolic Outcomes of ACTG 5142: A Prospective, Randomized, Phase III Trial of NRTI-, PI-, and NNRTI- sparing Regimens for Initial Treatment of HIV-1 Infection. Richard H. Haunbrich, S Riddler, G DiRienzo et al.
3 More information is available at www.medibolics.com
4 More information is available at www.nucleomaxx.com
5 More information is available at www.facialwasting.org.

FREE Built to Survive Spanish Translation!

We are happy to announce that the Spanish translation for the main chapters of Built to Survive are now available for free for all Spanish speaking people living with HIV who are dealing with body changes.

Este libro cubre temas sobre terapias anabolicas, testosterona, ejercicio, nutricion y suplementos para aumentar la masa muscular y disminuir la dispodistrofia en el VIH.

El libro esta aqui en el formato adobe acrobat reader ( obtenga adobe reader en adobe.com)
http://f1.grp.yahoofs.com/v1/EFLdRwmeBhxxAGzngylkZa5IgpKxXnsq3yidaK51U0yh5b4l_jbiYCkhCExDzZBrkY8eMTgyLN2rdVFObIX1/Fortaleceteysobrevive.pdf