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This Month in HIV: A Podcast of Critical News in HIV
  

This Month in HIV: 2009 Update on Body Shape Changes and HIV/AIDS

A Conversation With Dr. Donald Kotler and Patient Activist Nelson Vergel

April 2009

This podcast is a part of the series This Month in HIV. To subscribe to this series, click here.

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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.

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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

  1. 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.
  2. 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.
  3. 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.

Read more about Nelson Vergel:

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Copyright © 2009 Body Health Resources Corporation. All rights reserved. Podcast disclaimer.

This podcast is a part of the series This Month in HIV. To subscribe to this series, click here.


  

This article was provided by TheBody.com. It is a part of the publication This Month in HIV.
 
See Also
TheBody.com's Lipoatrophy Resource Center
Ask a Question About Facial Wasting at The Body's "Ask the Experts" Forums
More on Facial Wasting/Lipoatrophy

 

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