I'm Bob Frascino, and I am the founder and president of the Robert James Frascino AIDS Foundation. I'm an HIV specialist here in the San Francisco Bay area.
When were you diagnosed?
The virus actually found me in January of 1991 while I was performing a medical procedure on a patient with advanced-stage AIDS. I sustained a hollow bore needle stick and laceration injury and subsequently seroconverted a number of weeks thereafter, in spite of the fact that I did take AZT [zidovudine, Retrovir] as a type of early PEP [post-exposure prophylaxis] back in 1991. We didn't know a lot about PEP back then. I did take PEP but in spite of that still seroconverted. So that was in January of 1991.
And you started treatment?
I took PEP for the full six weeks and actually did not start antiretroviral treatment for a number of years. I am a clinical immunologist, and so I was following my immune status at the time, and, again, the only drugs that were available in 1991 were AZT and ddI [didanosine, Videx], and ddC [zalcitabine, Hivid] was coming along around that time. I decided not to take those drugs initially. So it really wasn't until my T-cell count started to fall around 1995, I believe, that I started taking antiretrovirals and then switched over to HAART [highly active antiretroviral therapy], which included the protease inhibitor drugs, following the Vancouver [International AIDS Conference] in the summer of 1996. I had been doing some of the research on protease inhibitors prior to that time and felt that they were worth a try, so as of the summer of 1996, I started potent antiretroviral therapy with Crixivan [indinavir] and AZT and 3TC [lamivudine, Epivir] at that time.
Yes. I switched over to d4T shortly thereafter when that drug came out and looked to have a higher threshold as far as resistance. [I] took d4T for a number of years -- probably five, six years or so, and had an excellent immunologic response. In other words, as far as maintaining CD4 cells, they were improving and did well as far as a virologic response suppressing viral load. So I stayed on d4T for quite some time, right through the period where we began noticing some rather bizarre and unanticipated side effects, including what we now know to be lipoatrophy.
You were beginning to see patients showing signs of this strange fat loss in their face and saw the accumulation by around 1998, 1999?
Yes, it was an interesting story. We had seen changes in the way people looked right from the beginning of the epidemic. But, of course, that was really wasting, which was really [a] loss of lean body mass, and wasting can make somebody look very cachectic and very skeletal appearing, and it's really due to uncontrolled HIV infection. We really didn't have a good control over HIV replication or HIV infection until the HAART medications came online in mid-1996. Wasting is caused by uncontrolled HIV infection and also by other conditions like low testosterone levels and poor nutrition, malabsorption, hormonal problems -- lots of different things that we were seeing early on in the epidemic.
So wasting had been there for quite some time. The news was that in 1996, when HAART therapy became widely available, there was this sort of, I guess using Alan Greenspan-speak, there was a sort of irrational exuberance over how wonderful these drugs were going to be. [For example], David Ho [Director and CEO of the Aaron Diamond AIDS Research Center in New York City] and his researchers wound up being Time magazine's man of the year that year, because he had helped bring protease inhibitors to the forefront. We really thought that by taking these drugs we could very effectively turn off viral replication to the point where we would perhaps be able to eradicate the virus. Initial projections back in 1996 were that we could eradicate the virus in perhaps three years.
So we thought, well, we will take these strong drugs no matter what they are, and no matter what they do to us, for a period of three years. We'll eradicate the virus, and perhaps we'll be cured. But, of course, that really was irrational exuberance.
As an immunologist, were you more skeptical?
No, at that point, because again, the science was catching up to the reality here. Up until 1996 we really did not have an antiretroviral that turned off viral replication effectively and for long periods of time. AZT and all these other drugs have very short-lived efficacy with lots of side effects, and here, by combining drugs, and using the newer classes of drugs, we really had something that looked very effective.
What we didn't realize, and really what probably the clinical immunologists and research immunologists realized somewhat earlier than others, was that HIV can hide in these immunological sanctuaries where drugs really can't get to them. HIV is actually a bit smarter than we originally thought it was. Even though we can turn off viral replication in many places in the body, because HIV can hide, and because it is immunologically protected -- being a retrovirus -- we really cannot eradicate this stuff. There are some very long-lived cells in the body where HIV can hide completely protected, and as long as we take these drugs, maybe we can keep the virus from reproducing. However, if we were to stop these drugs, the viral replication comes back with a vengeance, and this is what we learned.
So the thought was that these immunologic long-lived cells could live maybe 60 years, and so we would have to take these drugs not for three years to really burn out this virus in a human; we'd have to take them for perhaps 60 years, and this was obviously disheartening to those of us who were on the drugs, thinking that perhaps we would be off of them and cured in a matter of years. We're now looking at having to use them lifelong. And along this time -- this was during the 1997-1998 period, when the immunologists were discovering this -- along this time, we also started noticing these rather bizarre physical changes, and the thought was: Could this be related to the drugs? But we didn't know.
"I actually saw this entire scenario unravel and unfold from _both_ sides of the examination table, and I can tell you that the view from the different sides of the examination table is incredibly different."
It didn't make sense that it would be wasting?
It didn't make sense that it would be wasting. In fact, it wasn't wasting. We could actually measure lean body mass, and we could see that people were -- their lean body mean was actually getting somewhat better. We were also getting better at treating things like hypogonadism with supplemental testosterone. We were getting better with nutrition. People's appetites improved. We were getting better at regulating hormonal problems. So the wasting was going away, because we were controlling HIV better. Again, one of the primary causes of wasting would be uncontrolled HIV infection.
We were now controlling HIV infection, so the wasting was actually going away, but people's shapes were beginning to change. We didn't understand it at first, and this became this sort of term that we called "lipodystrophy," which I think, unfortunately, is a bad term. We started talking about lipodystrophy and fat redistribution, and it turns out that those are, we know now, probably not accurate terms, in that it wasn't so much a case of fat redistribution -- where we were thinking that fat from the arms and the legs and the buttocks and the face was going over and being deposited in the back of the neck in the buffalo humps or in the stomach, in what we used to call Crix-belly or protease paunch.
We were thinking that fat was going from one place and being deposited in another place and that it was all part of the same syndrome, and we called that lipodystrophy. In other words, the fat was not going where it was supposed to go. We know now that's really not the case. It's really two separate things going on. There's lipoatrophy, which is the loss of the subcutaneous fat, the fat just underneath the skin, and it's seen most frequently in the arms and the legs and the buttocks and the face. That's lipoatrophy.
Then there's lipohypertrophy, or fat accumulation, a totally different syndrome whereby fat accumulates in the abdomen and the breasts and the upper back or buffalo hump area. So these are two separate processes probably caused by two separate underlying mechanisms, and we have to think of them separately, as well. But they were appearing at the same time in people. People were getting fat stomachs and buffalo humps, and at the same time their faces were thinning out, their arms and legs were getting very skinny, and the veins were beginning to pop out. We were wondering, what is this? Could this possibly be related to the medications? And because the newest medications on the block at this time were the protease inhibitors, the terms like Crix-belly and protease paunch came out, and we started blaming everything on protease inhibitors because of the temporal association of them coming into widespread use.
However, in retrospect, we now realize it was really the thymidine analog, with d4T and the AZT drugs that were causing the lipoatrophy or the fat loss, and perhaps some of the other drugs are more involved with the fat accumulation process, but this was all happening at the same time. It was difficult to sort out.
It was a confusing and frightening phenomenon for patients.
It was very frightening for patients, because here they were getting an awful lot of bad news. They were getting the bad news that they were going to have to be on these drugs forever, and then suddenly they were coming up with unanticipated, bizarre side effects. We knew about maybe Crixivan causing kidney stones, and we knew maybe that ddI was causing some peripheral neuropathy. Well, now all of the sudden, they were coming up with big, swollen bellies and buffalo humps, and the face was changing, and people were becoming panicky.
However, that was from the patient's side, and, you know, living through this as I did, I actually saw this entire scenario unravel and unfold from both sides of the examination table, and I can tell you that the view from the different sides of the examination table is incredibly different. If I put on my HIV specialist hat at the time and looked at the patients that I was seeing, I would say, "Boy, I am so happy that we have got these new drugs and more and more protease inhibitors coming out, and we're getting better at combining them. I'm really seeing that your viral load is going down. I'm seeing your T-cell counts come up very dramatically, almost like Lazarus. I'm seeing the immune system recover and regenerate, and I'm so excited about this." I was learning about viral load determinations and how low could we get the viral load to go and how much reconstitution could we get of the immune system in the various T-cells. This was what was occupying the physician's mind.
We were, as I say, irrationally exuberant. We were very excited. It's the very first time after a decade of failures -- actually longer than a decade of drug failures and watching people die. We were seeing significant improvement in immunologic function and in virologic control, so from the HIV physician side we were very excited, and we were very occupied with those thoughts. And, yes, we'd see this swollen belly, and we'd maybe see faces changing a little bit. This didn't tend to affect the thought process of the HIV specialists, because they were so focused on having something, having an effective tool for the first time.
Now, if you jump to the other side of the examination table, and you think of this as a patient, and you're hearing, "Boy, I'm going to have to use these drugs for the rest of my life. They're not easy to take. I'm taking Crixivan three times a day on an empty stomach, which means I'm not eating for an hour before, two hours after. That's nine hours out of the day I'm not eating. I've gotten a case of kidney stones. My neuropathy is making it kind of hard for me to walk. Yeah, I'm looking good on paper, but I'm not feeling so good, and now I'm starting to look pretty terrible."
So from the patients' perspective, they were getting very, very scared, and some of the patients really didn't have any of the other, more significant side effects, say the kidney stones or the neuropathy. All they had was this change in physical appearance, and that, to them, was scary, because suddenly some of the patients were actually feeling better, but they weren't looking so good, so it was a complete paradox for them. I remember many patients around this time, having lived through the period when there was the AIDS look from the early eighties and into the nineties, basically seeing these very thin, cachectic people with canes walking up and down the street, often with Kaposi's sarcoma lesions that would be out on their face. You would immediately have an AIDS look. You'd know that that person was suffering from AIDS. You had the black spots that were clearly visible, the wasting. You knew that they had an AIDS look, and people were very afraid of that AIDS look. Everyone was afraid of getting AIDS and having that look.
Suddenly, we get these new drugs. There's all this great news. People are talking about the end of AIDS and how everyone's going to be healthy again. Then there's this new syndrome coming out, this bizarre new change with lipoatrophy causing this sort of hallowing out of the cheeks and the skeletal look of the face again. For years people worried that Kaposi's sarcoma was going to out them as having AIDS, since it was an unmistakable sign of AIDS, and then lipodystrophy comes along, or lipoatrophy comes along, and it marks their faces in an entirely different way. In a sense, it made all of their worst nightmares come true.
They were now marked with the new look of AIDS. It's quite easy for people who know much about this disease, whether it be an HIV specialist or a person in the HIV community. They know the AIDS look. They can look in a room of people, and they can say, "You're positive. You're positive. You're positive. You're positive," based on lipoatrophy. There is a classic look now, which is as unmistakable as Kaposi's sarcoma, and so the worst nightmares were coming true. They were, in a sense, more healthy, because these drugs were working; however, they had now developed the new AIDS look, which was very disheartening, as you can imagine.
So this was a very confusing time, and it was looked at very, very differently. The patients were becoming sort of puppet-cheeked and wondering what to do about it. Should they go in for plastic surgery? Should they do this? Should they do that? The physicians were thinking, "What are these surgery-seeking puppet-cheekers? What are they worried about? They're sort of narcissistic. They should just be grateful to be alive."
So it was looked at in two very different ways, and it really was pitting, I think, the HIV-positive patient against what he was hearing from his HIV specialist. As I say, there was reason for this thought on both sides of the exam table. I can see it from an HIV specialist point of view, where they were focusing their attention on how good the meds were [compared to before], and I can see it from an HIV-positive patient's view, where this is not good news.
This was scary. We didn't know where this was going to go. We didn't know whether lipoatrophy was going to be associated with other medical conditions, other medical problems. We now know that it's not, other than some mild things, but it's not associated with a life-threatening complication like an opportunistic infection or something along that line. It really is more of an image problem, but one which is incredibly important to those of us with HIV disease, so it was a very confusing time.
"The physicians were thinking, 'What are these surgery-seeking puppet-cheekers? What are they worried about? They're sort of narcissistic. They should just be grateful to be alive.'"
I know that some patients felt that they had to make a stark decision between quality of life, how they looked -- which, to them, on a day-to-day, moment-to-moment basis was every bit as serious as their health -- and whether or not to continue taking the drugs. Many people felt that they did not necessarily have the support of their doctor in even addressing that decision, that their doctor wouldn't understand.
Right, and that's actually true. It was very interesting, the discussions at this point, because, again, multiple things were moving simultaneously. Patients in essence were getting healthier if you look at their overall general health. Their energy levels were coming back. The wasting was going away. Their T-cells were getting better. Viral loads were coming down. They were actually getting healthier, and so they were becoming more active, and they were being told that they're probably going to live longer, and as all these new things were coming down the pike, they were beginning to look different, and this was obviously bothering them.
The physicians, obviously, were very busy with HMOs coming into the picture and cost containment. Simultaneously, there were new tests, whether they were the new supersensitive viral load tests or resistance tests, and physicians were learning how to interpret them. Plus they were learning about how the new HIV drugs interacted and which drugs could be used. Their job was getting more complicated on the pure medical side, and they were putting, as often is the case, they were putting quality-of-life issues to the side. There just wasn't time in the 15-minute, 20-minute visit with the doctor to really go into the fact that your face was maybe a little bit more wrinkly, or the veins on your legs were sticking out a little bit. I mean, the docs really would tend to push these issues aside as not important enough to spend much time on. Plus, the physicians were thinking, "There's nothing I can do about that. You obviously need these drugs, so you've got to take them, so, you know, there's nothing that I need to do about that."
Even in the medical meetings, from the HIV specialists' point of view, if these issues were brought up, the doctors in the audience, with their nice fleshy cheeks, wouldn't think too much about this. They would prefer to go to the seminars that had to do with the latest resistance test or viral loads or drug combinations or drug-drug interactions.
However, from the HIV patient's point of view, if I take off my HIV specialist hat and put on my patient's hat, and [recall] people that I came in contact with or lectures that I would go and give or support groups that I would go and speak at, this was undoubtedly the hottest topic out there, and it was being totally, or, for the most part, ignored by most of the specialists. Really there were a lot of reasons why patients, at that particular point in history, in the history of the AIDS epidemic, did not want to look like they had HIV, and I remember talking to a lot of them about this.
For one thing, the patient says, "I'm starting to feel better, and I may even live longer and have to pay my credit card debt that I've run up, and so I don't want to look like I've got HIV, because I don't want to be treated any differently. I don't want to be treated like a person with a disease. You know, I'm still working. I'm feeling better. My doctor says I'm getting better immunologically. I don't want to be treated like a person with a disease."
Also, the patients wanted to choose who and when to reveal their HIV status. I mean, they would hopefully have their support group. They would have their friends, family. They would choose who to tell they were HIV positive to. They may not choose to tell the general public that they're HIV positive, yet having this look, having this lipoatrophy look, was in a way outing them to the general public. [As] an HIV-positive person, I can tell you that when somebody knows you're HIV positive in the general public, there is less casual contact, if you will. People just know that you've got something, and it sort of makes you feel abnormal and some people can make you feel essentially unhealthy, so it's a bad feedback loop there.
So there's this whole concept of not wanting to be treated like a person with a disease. You're sort of wearing this disease right on your face. Everybody looks in the mirror before they go to work in the morning to check and make sure that their hair is combed properly, that they've got the right outfit on or whatever. Living with HIV, every HIV-positive person realizes there's sort of this cellular battle, this cellular war, going on inside of them all the time. However, when their face begins to change, they often feel like they're starting to lose the battle, if you will, and how someone looks is very important to them.
If you took one of these fleshy-cheeked HIV doctors, and you gave them some type of physical thing such as a nice, big pus-filled pimple on the tip of their nose, sent them to work and then asked them what their workday was like. You know, it's only a pimple. You know, it'll pop and go away in a few days, but today you're going to work with that big, pus-filled pimple on the tip of your nose.
You then would have to go in and see patients, and look at people. When people look at you, they're going to say, "Oh, my God, you've got --." You know, they may not say anything to you, but they're going to give you this sort of raised eye look like, "Oh, my God, he's got that big, horrible, pus-filled pimple on the tip of his nose. You know, I don't know if I want to get that close to him. I don't know if I want him that close to me when he's looking in my ear and looking in my throat. You know, that thing could pop. You know, it looks like it should have orange cones around it or something."
But something as simple as a pimple could ruin that doctor's day or any person's day, any non-HIV-positive person's day. A bad hair day can ruin a person's day, and yet you think about your face, and you think about all these lines, these nooks, and these crevices and the skeletal look, and you look sick. So that really has an intense emotional impact on the individual. Then you could take a step farther than that, and you think about sex. I mean, people that are HIV positive are already sort of sexually hog-tied and not in a good way. I mean they already have to be -- sex is more complicated for them, and if you think of this altered look to your body, whether it be the skinny arms and legs and the veins or the skeletal look of the face, you become more self-conscious.
So there's nothing worse than self-conscious sex, and will it even sort of repel a potential lover? As you become involved with somebody, this person you're becoming involved with has to have some faith in the person's longevity -- that they're going to be around. Nobody wants to sleep with a bag of bones and a skeleton.
So the whole sexual part of it gets tied up into it, and it's just, you know, AIDS, from an HIV-positive person's standpoint. It's sort of like this chronic endurance test. It's a merry-go-round ride that, once you're HIV positive, you're on the ride, and you're never getting off, and so you've got to hang on for the rest of your life. So you're on this endurance test to begin with. It's terrifying when you start to see your face change, because that's the image of yourself. If you look in the mirror, and you don't recognize yourself, I think your personal image can begin to slip away, and this is what was happening right around that time.
This was the talk that was in the patient support groups and patient groups that I would go and speak to. Probably around 2002 or so, there was at least one large survey that showed that upwards of 75 percent of HIV-positive people said that they would rather go off their meds and risk their health, rather than have lipoatrophy and look like a freak.
I remember talking to patient groups at this time, and the general consensus was, in a perfect world, facial wasting would sort of be worn as sort of a badge of courage. You know, these were your battle scars from doing battle in the AIDS war. I mean, after all, these people have been through hell and back again. They're actually getting better now, and these are the battle scars, if you will.
But it wasn't a perfect world. It was really a world where people look at you and make judgments based on how effective you can be in the workplace, how effective you can be as a potential friend, partner, whatever. Basically, this look was [doing] everything from [scaring] friends and family to affecting people's work performance, and, again -- because the fear was so great that we didn't know where it was going -- it was actually affecting how somebody felt about their medications, their relationship with their medications, if you will, to the point where adherence and compliance was being significantly compromised.
"It was only at this point, when patients really started to make this \[lipoatrophy\] a very significant issue, and compliance with medications became a problem, did the HIV doctors begin to take note of this."
It was only at this point, when patients really started to make this a very significant issue, and compliance with medications became a problem, did the HIV doctors begin to take note of this, because suddenly viral loads shot up, T-cell counts started to drop, and they would talk to patients. We would talk to patients, and they'd say, "Look, I'm not taking these drugs anymore. My lover walked out on me. My family won't speak to me. I feel terrible when I look in the mirror. I'm not going out anymore. I don't want to live this way."
It had come to that -- it became a choice between the drug or this really abnormal life that they were living. Because of the lipoatrophy, they were going off the drugs, and it was the time during the strategic treatment interruptions, and we thought those were a good idea. People were jumping on board thinking, "If I can get off these damn drugs for a while, maybe my face will come back," and that's one of the things that pushed that whole movement, as well.
So, this was when the HIV doctors suddenly said, "We've got to do something about this. This is a very significant problem, because it's affecting medication compliance," and, again, there were more and more people involved now. They weren't seeing it just in the occasional patient, because almost everybody was on d4T or AZT at this point, and they'd been on it for a longer number of years, so we were seeing more and more of the complications of lipoatrophy and fat accumulation.
So the mood began to change, and once again it was the patients who helped push the change. Then the doctors began to realize that quality of life and physical appearance was important, even though it wasn't medically a complex issue for them from an HIV perspective. From an HIV physician's perspective, this wasn't something that was going to be like out-of-control diabetes or a cardiac crisis or any of those kinds of things. However, it was a quality-of-life issue which was brought to the forefront as being equally important in that it had to be part of every treatment equation now, and I think we're beginning to realize that more now.
Did you begin to experience lipoatrophy yourself?
Yes, I did. My story was interesting. I've been with my lover, Dr. Steve Natterstad, for over 12 years. I think because I was in a stable relationship, I didn't have quite the same intensity of reaction to this that other people did. I also was very open about my HIV status and used it as if it were battle scars. I used it to talk to other physicians about HIV, talked to patients, used it at fundraising events to say, "Look, HIV does change even the way you look. These are my battle scars." I was happy to wear my battle scars out in the open, but I think I was in the minority there. I think, again, part of it was because I was already open about my status and I was involved in a very stable relationship and still am, thankfully.
So my situation was a little bit different. Now, where I was beginning to have problems: I didn't like shaving in the morning and having to go in and out of all the nooks and crevices and noticing that I was looking different there. I think it really came home to me when I was going over to Europe quite a bit to give lectures and do research projects. I remember there were several occasions where I went to get on a plane, international flight, and when they checked my passport, the gate agent said, "Oh, you don't look like your picture." My passport picture was only a few years old, and I started to look at my passport picture and said, "You know, you're right. I'm not looking like that anymore."
So then it began to bother me a bit more. Had I changed that much that someone who doesn't know me can look at a picture from even several years ago and say, "You don't look like your picture anymore?" At that point, I decided I was going to do something about it. I had been getting an awful lot of questions from patients and patient groups about facial fillers at that point. We knew that certain drugs might be involved with this. We were also beginning to learn a little bit about mitochondrial toxicity and drugs.
Different things were coming up, but we were learning that this was not going to be a problem which goes away quickly. There was a question about [whether we should] start doing plastic surgery. Should we look at silicone injections? I was asked as a clinical immunologist to look into this many times, because [in terms of doing plastic surgery on an HIV-positive person], here we have somebody with an abnormal immune system, and we're thinking about adding something to the face as a restorative type of procedure. Was this going to affect them immunologically? So I did a bunch of research on that, looking to see what products were out there, what could possibly be used, what experience had people had. Europe was far ahead of us in this game.
Why do you think that is?
I think that that's a long, complicated question. It has to do with our FDA [U.S. Food and Drug Administration]. It has to do with the focus that the physicians in Europe had, compared to the focus that American physicians had. It had to do with research dollars and where they were being placed, and so there was a combination of factors. Europe and other industrialized countries have been far ahead of the United States in HIV prevention methods, as far as education is concerned. Safer sexual education messages have been much better in other countries compared to here, and they were ahead of the curve here in treatment of lipoatrophy.
That being said, there are places where plastic surgery has always been a much more prevalent treatment than here in the United States. For instance, South America. If you go to Rio or Buenos Aires, plastic surgeons are everywhere. It's just much more common to have plastic surgical procedures. Now, they were prevalent in Beverly Hills in the United States, but they weren't as prevalent in other places. Some of these agents were being used for more minor plastic surgery procedures in other countries more readily, [since] they had more experience [with] them. So when the HIV problem showed up, they said, "Well, we ought to try these," and because of regulations and whatever there, it may be easier to try them in other countries than it is in the United States.
Again, there was the interest. Patients were pushing in other countries a little bit harder than they were in this country, as well, or at least, the physicians doing the research and the drug companies were listening more in some of the other countries than they were here. So for a variety of reasons, we were behind the curve there and still are. There are more products available for treatment of this problem in other countries than there are here in the United States, which is unfortunate, but I hope it's a temporary situation and that we'll begin to catch up.
At what point did you decide to have restorative procedures done? Presumably this was after doing all of that research?
Yes, it was after doing the research and talking to patients, because I would talk to patients about whatever the hot topics were, and the hot topics at that time really were lipoatrophy, even though it wasn't called that at the time. It was lipodystrophy at the time, but they were concerned about this, and they wanted to know what they could do about it, what would be safe to do, what the cost would be, and whatever, so doing the research from that perspective.
I had the treatment done -- gosh, I don't remember the original year. It's been a number of years now. It was before New-Fill [poly-L-lactic acid, Sculptra] was approved here in the United States. I had to go to Europe to actually obtain the product. However, there was a plastic surgeon here in San Francisco who had had considerable experience administering the product. So I went and got the product overseas and brought it back to the United States and had it administered here by a plastic surgeon in San Francisco, and that worked.
It worked very well for me. I felt it was rather remarkable; actually, the change occurred over a number of months. I recognized that change, really, in other people's response to me, people that I didn't see for three or four or five, six months, who would come up to me and tell me how good I was looking, wondering whether I'd had a new haircut or a different moustache or goatee or, you know, what was different? They couldn't quite pinpoint what was different, which was good. I mean, it really meant I was getting my face back again, and that was very encouraging to me.
****"I used New-Fill \[Sculptra\] because immunologically it's an inert substance, and so to me, as an immunologist, it made the most sense \[in terms\] of the things that were available at the time to use a substance which was inert and that was biodegradable."****
So I talked about this quite a bit. I used New-Fill because immunologically it's an inert substance, and so to me, as an immunologist, it made the most sense [in terms] of the things that were available at the time to use a substance which was inert and that was biodegradable. It actually gets reabsorbed and is taken out of the body. So this, to me, made good sense. But it also was what we consider a temporary filler, because the thought was, well, if we do figure out the cause of lipoatrophy, and it can be fixed, then, you wouldn't want to have a permanent device placed into your skin and then need to have it removed, because your cheeks would come back to normal again, because you would then get your own fat back again.
So the thought was, in my mind, is I wanted something which was temporary, because I wasn't sure where this whole story was going, particularly at that particular point in history. Secondly, I wanted something that was the safest product and the most immunologically inert product so that it wouldn't be doing any more damage to the immune system. So that's why I chose New-Fill at the time, and, as I say, I've been very happy with that particular product, and it turns out it's the first one that the FDA has given approval to in the United States.
It's no longer called New-Fill. It's now called Sculptra, and from the original small European company that was making it, it's now been taken over by Dermik, which is a subsidiary of Aventis. Not unlike other stories, the moment the bigger company got a hold of the drug, and the FDA licensed it, the price quadrupled. So what I used to pay $125 for now costs $480. That's just for the product, not even the administration of the product. So the cost quadrupled. Again, it's just another example of, I would think, price gouging, which is, to my mind, a bit unconscionable and began all the way back with the original AZT story, so it's just still continuing. So that's become an ongoing problem, and it is the only one that's available here in the United States so far.
It's almost impossible to get your insurance to cover it.
Yes. That's, again, an interesting issue. This has been an ongoing problem for years -- the difference between whether it's really cosmetic or whether it's really restorative. To my mind, there's no doubt that this is really a restorative procedure. However, there are insurance companies, obviously, not wanting to reimburse for it. I think there's a very good case to be made, and I continue to make this case: that facial wasting really, really does qualify for reconstructive rather than cosmetic status. I think we need to continue to make this case to the insurance companies and also to the state and federal payment programs.
There's a distinction that reconstructive procedures tend to restore to baseline condition the result of medical disease or a trauma. In other words, you're trying to put something back to the way it was, whereas the real definition of a cosmetic procedure is [that it is] really carried out sort of to enhance the appearance of something that starts at baseline. So, you've got a wrinkle, and you want the wrinkle to go away, so you're enhancing your appearance by a cosmetic procedure. Whereas, as I say, a reconstructive procedure is really putting something back to the way that it should have been to begin with.
There is a health and safety code that talks about reconstructive surgery, and it really talks about it being able to correct an abnormal structure, which is like facial wasting, and that's really caused either by things -- they list things like congenital defects or developmental abnormalities or trauma or infection or tumors or certain diseases, and they say that the reason to do this reconstructive surgery is to create a normal appearance to the extent possible. Well, that's exactly what we're doing with facial fillers, and so it really fits the California health and safety code, and there are similar codes in other states. This is the current rationale that I'm using to try to push health insurance companies to pay for it.
So the problem is that it's not a drug, so it's not covered by ADAP [the U.S. AIDS Drug Assistance Program, which pays for the HIV and related medications for uninsured or poorly insured people with HIV] or any of the drug programs. It's really a device, and so the fact that it's a device is why we're having trouble actually getting it covered, because devices are covered in a whole different way than drugs. So it's a substance which is injected, and then it's reabsorbed, and it goes away, yet it's still considered a device or an implant, if you will, and so it's fallen between the cracks, but it's really just a question of semantics.
There's no doubt in my mind, from the medical perspective, if you look at the true definition of reconstructive procedures versus cosmetic procedures, this absolutely qualifies as a reconstructive procedure, same thing as breast implants or other things after cancer. You're restoring something to its baseline condition. You're not improving something. You're actually restoring what has been lost, and it's been lost due to the drug effects of the treatment of HIV disease.
So I think there's still an argument to be made, and I've not given up hope that we will be able to get this and other treatments for lipoatrophy covered. I think part of it is, again, changing the physicians' perspective into them thinking of this, really, as a reconstructive procedure and not as a cosmetic procedure, because the docs really have to do the fighting -- as well as the patients -- with the insurance companies to actually convince them that this needs to be done for a variety of reasons. So that's the story there.
I've heard that some people have been successful appealing it to their insurance company when they've been able to document in great detail the psychological cost of it, the ways in which it has affected their mental health and their ability to function.
"We have gotten payment from a whole variety of insurance companies, but it really requires the HIV specialist to go to bat for the patients, to document the trauma that's been induced by this \[lipoatrophy\]."
Right, and it's true. We have gotten payment from a whole variety of insurance companies, but it really requires the HIV specialist to go to bat for the patients, to document the trauma that's been induced by this. First of all, to document the degree of lipoatrophy, because it's not something you can show on an x-ray. You have to really document in the medical record that this is a significant problem, that there's been a significant change, and it's directly related to drug therapy, and that because of this significant change, the patient is experiencing social withdrawal, depression, maybe, perhaps medication compliance issues, and then really document all that, and then submit that to the insurance company.
Then the patient has to submit the information that I told you about, the fact that the health and safety codes clearly indicate the difference between cosmetic and reconstructive, and what they're asking for is not an enhancement from baseline. They want to go back to baseline. Something has happened to them which has changed their baseline features -- the same thing as having a breast removed. What they want to do is get back to baseline, and if they're going to cover breast replacement, then they're going to have to cover things like lipoatrophy treatment, as well, because the philosophy is the same, and there really should be no distinction between those, and there is no rationale for a distinction between them.
So, again, unfortunately, the HIV patients are going to have to become activists, and it's going to be the physicians who are going to have to do the documentation and write the referrals. And again, most HIV doctors are just too busy to take this on without giving them a significant push, and so the patients have to push their specialists, and the specialists have to realize that, yes, if they do this, that they can get it covered, and so that's where we are right now.
In terms of other options for reconstructing or restoring your face, what are some of the products that are available in Europe or elsewhere?
There's quite a variety of them, actually. Basically, how do you treat lipoatrophy? To begin with you want to try to prevent it, obviously. So for people that are newly diagnosed, if they can prevent lipoatrophy, that's the best thing. They can do that. The best we know right now is that they can do that by avoiding the drugs that we know are closely associated with it. Now there are other factors that may increase or decrease the risks for lipoatrophy, including age and gender and genetic predisposition and T-cell counts when you start therapy and all sorts of other things that get taken into consideration, but I think HIV specialists are pretty well aware of that now. I think they're pretty well aware of the fact that if they avoid the thymidine analogs, the AZT, or the d4T, and possibly ddI, that they'll have a better chance of avoiding lipoatrophy, so that's number one. A second thing would be that if you're on those drugs -- if you're on Zerit or Retrovir -- to switch off of them so that you won't be making the lipoatrophy any worse.
So those are pretty common. Then if you get to the, sort of the restorative therapies, you're really in the realm of facial fillers or implants. Generally speaking, the facial fillers are injectable, or sometimes they're surgically inserted, but they're a small procedure. They're used to fill in the hollows in the face, and they can be divided in lots of different ways, and I'll just give you one way. You can divide them between organic versus synthetic [fillers], and the organic fillers are those which are, shall we say, naturally derived. They're either derived from humans or animals or botanicals -- from plants -- and these are, in general, biodegradable.
Do they all work in a similar way as Sculptra works?
No, they actually work somewhat differently, and I'll run through a few of them for you and show you. But the synthetic fillers are generally more man-made products, and they're not biodegradable. So [that is] the big difference between organic versus synthetic. Then [there is another] way to look at these: temporary fillers versus semi-permanent fillers versus permanent fillers.
They're temporary [fillers] if they can be broken down and removed from the body over time, and the process can take weeks to months. As I mentioned, the Sculptra or New-Fill that I had done is a temporary filler in that it is broken down and removed from the body totally. The semi-permanent fillers are not readily broken down. However, they can be removed from the body with either a small procedure, or if there's something that you didn't like the appearance of, you can take these out relatively easily. If there's a side effect or dissatisfaction or whatever, you can get them out, even though it may require another procedure. The permanent fillers are much more difficult to remove. Once they're in, they're in, and if you're unhappy with the result, or a problem arises, they're still in, and you can't really get them out.
So which is best? I think most experts agree you should sort of stick with the temporary or semi-permanent fillers when you're treating a condition like lipoatrophy, which is a condition we're still learning about. It's a condition that may change as far as the way we treat it in the future, a condition that may change now that people are off d4T and AZT, that maybe some of their own fat's going to come back over time, over a number of years, so we're really looking at doing something now that should be in the temporary or semi-permanent category.
What's your view on the reversibility of lipoatrophy? Do you think that the fat does return?
Slowly, extremely slowly. I think we've got good clinical data now to show that it does come back, and we've noted it more, actually, in the extremities, the arms and the legs, than we have in the face, but even in the face there has been some improvement, but it is very slow. The reason that this is a difficult issue to discuss is because we don't really understand [the reversibility of lipoatrophy yet].
We know that something goes wrong with the fat cells. The "adipocytes" are what we call them medically. The adipocytes are the fat cells that actually control where fat is stored and how it works, and we know that d4T and AZT and thymidine analogs and perhaps ddI do something to these adipocytes. They actually change the mitochondria, which are the little powerhouse factories inside these cells, and they could actually destroy these fat cells.
That's what they call apoptosis (programmed cell death), where these cells are actually destroyed. If the cells are destroyed, it's going to be much harder to replace them, to make new cells. If you're only changing the fat cells, changing the functioning of that cell, well then by taking away the offending agent, taking away the thing which is damping down the mitochondrial processes, well then that may come back over time, and so we're looking at both things. You know, some of these cells are probably destroyed and gone. Some of these cells are probably just functioning abnormally. We still don't know, and it may be different from patient to patient.
But I do think that there is good evidence now, a number of years out, from people from these switch studies that fat is returning; however, it may take years and years and years and years and years and years and years before it gets back to normal, if it ever does go all the way back to normal. So with that very long timeline, even with an optimistic view, I think that having to do something now is going to be on people's minds and probably certainly necessary.
So, what are some of the fillers? Well, when you talk about the temporary ones, the most common one probably would just be the autologous fat transplant. That's just taking fat from one part of the body, such as the butt or the hips or the inner thighs or the abdomen, and then you sort of clean it and filter it, and you inject it into another part of the body like the face, and this has been around for quite some time. It's very natural. You're taking your own fat from one place and injecting it into another place. It has a very sort of a natural appearance. The trouble is, with HIV patients, that it's difficult to harvest fat from parts of the body, because we don't have a lot of fat. Then the post-surgical recovery from this can be rather uncomfortable, so this doesn't tend to work all that well. The results are temporary. It's fairly pricey, but it certainly is available, and it's probably the first thing that was tried.
The next thing that probably was tried, and it's still used in some places, is collagen, and collagen's probably been around for a good 25 years or more as a cosmetic procedure, mainly for treatment in facial wrinkles here in the U.S., but collagen is really derived from [calves], young cows. It's from their skin, and it's really a component of the skin, and there is also human collagen that can be grown in tests tubes that has been used, as well. But, the problem with it, if you use the regular collagen -- the bovine collagen, the one that comes from calves -- there is [the possibility of] an allergic reaction and some scarring. It's also expensive. Also, collagen, whether it be human or bovine, is relatively very temporary. It only lasts maybe three months or so, and so the annual cost turns out to be very, very high, and you have this sort of fluctuating up and down look to yourself as the stuff wears out so quickly. So, that's around. It's very temporary. It's also reasonably safe -- aside from the allergic reactions.
There's another product out there that's actually taken from human cadavers. It's really using sort of the lining that comes over the muscles called the fascia, sort of a gray-white covering that goes over the muscles. This stuff is harvested at the time of death and sort of purified and then injected. There's a bunch of names for it. It's available in different places. It's not approved by the FDA here for treatment of facial lipoatrophy. It's very temporary. It's very expensive. I've seen some initial good responses from it, but, again, it's very, very temporary, and probably people have had it done, so they sort of felt like dead man walking, you know, the idea of having cadaver parts injected into them.
Another one, hyaluronic acid, [is] the only one that's approved here. There are several different types. Perlane and Hylaform are available in Europe, but in the United States it's called Restylane, and Restylane is hyaluronic acid. It's really found in what we call connective tissue in humans, and there are a bunch of different brands. It works to a certain extent. It's cheaper than a lot of the other products. It can be removed in case there are side effects or dissatisfaction with the results. I think the biggest thing is that you have to inject relatively large volumes of the stuff, and it's very uncomfortable. It's a little cheaper than some, but you're still looking at a reasonably sizey price tag, and there's not a lot of experience in using it for this particular condition, but Restylane is available in the U.S.
Radiance is another one. It's a calcium product, really, hydroxylapatite calcium (Radiance). It's a synthetic product, and it's really a product which is found in bones and teeth. It's used in the reconstruction of bony structures. It's been tried for lipoatrophy, but it's expensive, and it causes nodules and lumps and bumps. I've not seen good responses to this, and they're still exploring how it could be used in facial lipoatrophy, but, as I said, have not seen good responses to it so far.
Then the New-Fill that I talked about before, which is really poly-L-lactic acid, that is available in the United States. It's a synthetic product. It's got a very long history with use in reconstructive surgery around the world, Even though it's synthetic, what's interesting about it is that it is broken down and completely removed from the body, so its effects really are temporary.
It actually works in sort of an unusual way. You inject this stuff in, and then it actually stimulates the production of your own collagen. So it works in a slightly different way than many of the other products as far as you're not just putting the stuff in, and that's what's making your face look better. You're actually putting something in which causes your own skin to make its own collagen in response to these little particles that you're injecting. That collagen actually thickens the skin, and by thickening the skin it gives the skin more volume, which then in essence sort of fills up those hollows and those wrinkles. So it's a different approach. It's more natural in that it's your own skin and collagen that you're feeling, rather than, say, a pure implant or silicone type feeling, and, as I say, it is temporary.
I've had good results out beyond two years with this product. It may take three or four or five sessions, depending on how severe the lipoatrophy is. But once things are pretty much complete, it stays intact for a good period of time. Some people say that they require touch-up as early as maybe 18 months or so. I've certainly seen it out beyond two years, and I've had beyond two years of good luck with this product.
So the collagen both fills the place where the fat cells were, but also it somehow thickens the skin, too?
Yes, what happens are two things. When you first inject the stuff, it has to be injected into a certain level of the skin. The skin is not just a thin sheet. It's got all these different layers, and the different layers have different functions, and so you inject this into a certain layer of the skin, which then stimulates the production of collagen, which is in itself a layer of skin.
That stays around for quite some period of time, and as I say, it can fill in larger and larger indentations, but the more that it has to plump out, the more individual sessions you would need with injecting the Sculptra, because you can only inject a certain amount at a time.
Other products you can put in the entire dose and correct everything in one procedure, but that's not the way that Sculptra or New-Fill works. You do it in stages, because you have to see how the collagen production actually fills in the wrinkles, and then you add a bit more and add a bit more.
For example, how many sessions did you require?
I had six sessions total. This includes my touch-up sessions. It took me four sessions to really get to where I wanted to be, and then I've had a couple of touch-up sessions since then. I've seen good responses with fewer sessions -- it depends on whether you have a mild, moderate, or severe case going in how many sessions it'll take to really give you the look that you want. If you're going for a complete Tom Cruise, Brad Pitt look, it may take a few more sessions than if you just want to go back to your original look.
There are products, other than the ones I mentioned, that are available; however, as far as "temporary fillers" go, these are the ones we've had the most experience with. Turning now to "semi-permanent fillers," the semi-permanent ones are becoming more prevalent, particularly the silicone ones. I've seen a lot of ads for those recently, and it's a bit more controversial as far as how safe silicone really is. [The silicone] approved here in the United States is really for an optical procedure, an eye repair procedure, and it's only being tried for lipoatrophy on an experimental basis, but it's very long-acting.
Silicone has really been used for a variety of different purposes over the years. Everything from lubricants on down are made from silicone, but injectable medical-grade silicone is being used for these restorative procedures now. The big thing is it really can't be removed very easily, and using too much of it can be damaging to the face. I've seen some bad reactions with it in that it can migrate a little bit, and if it starts up in your cheeks and migrates down to your jaw, you wind up with jowls instead of cheeks, and this is not a good thing.
The tendency for things to go wrong, such as migration, does that have to do with both the quality of the silicone itself and also the actual administration?
I think it really has more to do with the administration and the disease process. Having an experienced person is probably the most critical thing to getting a good response with any of these products. With silicone, I think there's more danger in that if this is put in improperly, or too much is put in or whatever, that it can migrate, and that, since it's essentially a semi-permanent type of product, you can't get it out. So it really, I think, has more to do with the skill of the person administering the product rather than the product itself.
The risk with the product itself is whether or not there are immunologic reactions to silicone and other potential things that can go wrong. But I think this migrating type problem is really probably [an issue of skill] -- it's not just stick a needle in and inject the stuff. It really requires the skill of a plastic surgeon to make sure it's going in properly, and that goes for any of the semi-permanent or permanent fillers. You can have problems with them not being installed properly or surgically placed properly and then have the difficult problem thereafter of, "Now what do I do, that I've got jowls instead of cheeks?" You know, or, "One of my cheeks is down, the other one is up."
There's a whole pile of other things: everything [from] products that are equivalent to Gortex that are being used that require little minor surgical implants and stuff that -- Articol, which is really like plexiglas or the stuff hard contact lenses are made out of, [consists of] little micro spheres that are put in, and these little spheres are coated with bovine collagen themselves. The bovine collagen is removed, and the body replaces it with its own collagen, and you've got these little plexiglas spheres holding it into place.
But again, all these things are not readily available. They're not FDA approved. You can go to Mexico and go to Brazil and get them done no problem. There they are definitely approved. The cost is fairly high, and I think when patients begin to look at these various products, they should look to see if they can be removed if something goes wrong. They should evaluate the potential side effect problem, the general overall cost and the durability of the particular filler that they might be considering -- so there's quite a few [things] to consider.
Bio-Alcamid is another product that's trying to make inroads here. Again, it's not available in the United States yet, but easily available in Tijuana and Canada and other places. It's a synthetic product, as well, and it uses sort of a high volume of this synthetic polymer which is injected. It's been used in Europe for quite some time, but [there is] very little scientific data supporting the safety or efficacy as far as lipoatrophy and really no data here in the United States that's been published yet. So still much more to learn about these products, but at least there are more potential options out there, which is a good thing. There's more attention being paid to these products. Which will wind up being the best one three years from now, five years from now, seven years from now? I don't know.
My personal experience right now, I would still tend to lean toward products that are temporary, that are biodegradable. For me, immunologically inert was important, and so Sculptra or New-Fill would fit that bill. The only thing I don't like about that product, the thing I disliked about it most, is its bill, the fact that the company increased the price by 400 percent, which again I think is unconscionable, and we need to work on that. They do have a patient assistance program, so you could call and find out if you're poor enough to get assistance in helping to get it covered, but again, unfortunately, it's pricing itself out of many patients' means, and that's too bad.
Looking on the horizon at possible actual treatments that would reverse this or that would help restore the mitochondrial function, is there any promise there at this point?
Well, we're looking. It would be helpful if we understood more of the complete pathology. In other words, if we knew that this was only altering the functioning of the mitochondria, then we would go after it in one way, maybe with uridine, for instance, which is being looked at. But if we find out that this is really something called apoptosis, where these adipocytes are actually being lost, they're being destroyed, then we have to look at entirely different types of potential permanent fixes. So we're a little ways away from that yet.
In the distant future do I hope we're going to be able to do it that way? I think yes. I think the problem right now is that the impetus isn't there to look too hard, because we have, in a sense, identified some of the culprits that are largely associated with the increased incidence of this. In other words, we understand the thymidine analogs, d4T and AZT, are what was really driving this epidemic of lipoatrophy, and by avoiding those products -- we now have other HIV drugs to choose from -- maybe we won't be seeing as much of this, and in essence, that is true. On the newly diagnosed patients who come in and get treated with, say, Viread [tenofovir] or abacavir [Ziagen] instead of Zerit or AZT, we're not seeing as much lipoatrophy. So there isn't a real big push to completely understand the science behind this problem, and until we understand that, there's not going to be a push to get a cure for a problem that may not be all that prevalent in the future.
As an HIV health care provider and a person living with the virus, Dr. Frascino has a unique perspective. As someone who has struggled with lipoatrophy himself, he knows all too well what his patients are experiencing. Dr. Frascino is president and founder of The Robert James Frascino AIDS Foundation, in Los Altos, Calif. He has also founded two medical clinics devoted to the comprehensive and compassionate care of people living with HIV. As primary investigator in numerous HIV clinical trials, he has published articles on evolving new treatments and quality-of-life issues for HIV-positive people.