Interview with Lipodystrophy Expert- Dr David Nolan

By Nelson Vergel

May 2005   HIV related lipoatrophy (fat loss under the skin) is a clinical problem that affects many people living with HIV. Lipoatrophy can cause substantial loss of buttock tissue, veiny legs and arms, and facial wasting. Lipoatrophy can happen alone or in combination with lipohypertrophy (fat accumulation) in the visceral (organ) and dorsocervical (back of the neck) area.  These body changes with or without blood level alterations of cholesterol, triglycerides, lactic acid, glucose, and insulin is what is called HIV-related lipodystrophy syndrome.  Many of these body changes occur normally with aging, but being HIV positive seems to accelerate this problem at earlier ages. Many observational cohorts  and  studies to determine the causes and potential treatments of lipodystrophy have been performed since 1997, the first year when we realized that living longer with HIV may be accompanied with side effects like body changes.  Even though there seems not to be a consensus based case definition for lipodystrophy, there are many things that we have learned since then.  One of them is the potential negative role of nucleoside analogs like Zerit (D4T, stavudine) and AZT (zidovudine) on subcutaneous fat wasting.  Studies in which patients were switched from these drugs to Abacavir (Ziagen) or Tenofovir (Viread) have produced encouraging results in reversing lipoatrophy, even if it is at a slow rate. Other studies looking at using insulin sensitizers like rosiglitazone (Avandia) have produced conflicting results in reversing lipoatrophy. It seems that the use of Avandia in combination with Zerit or AZT does not allow for regrowth of subcutaneous fat tissue. Fortunately, good news came to patients with lipoatrophy in the US when the FDA approved Sculptra (polylactic acid) injections in August 2004 for the treatment of HIV related facial lipoatrophy. Although this option does not treat the root cause of the problem, it can give patients hope to look healthy once again. There are still many unanswered questions and misunderstandings in the field of lipodystrophy and metabolic disorders in HIV.  That is why I am glad to have the pleasure to interview one of the leading researchers in the field of metabolic disorders in HIV. I have seen him in every conference that deals with lipodystrophy and side effects and have always been impressed with his knowledge and his strong stand on the effect of HIV medications on body changes. David Nolan is a clinician and researcher based at Royal Perth Hospital in Western Australia, where he works at the Centre for Clinical Immunology and Biomedical Statistics. He has a broad range of interests relating to HIV and its treatment, with a particular emphasis on lipoatrophy where he has explored associations between NRTI therapy, mitochondrial toxicity and fat tissue pathology. He has published more than 30 research papers and reviews, covering the broad topic of lipodystrophy as well as related topics including mitochondrial toxicity syndromes, metabolic complications of HIV protease inhibitor therapy, hyperlactatemia syndromes, genetic susceptibility to abacavir and nevirapine hypersensitivity reactions, and the effects of HIV and treatment on bone density. 

1-      Can HIV itself cause lipoatrophy or mitochondrial dysfunction in treatment naive patients? If so, can starting treatment with non-thymide analogs like tenofovir or abacavir reverse it?

There is no evidence that HIV infection itself can cause lipoatrophy.  It has been known for some time that severe immune deficiency and AIDS-defining illnesses can be associated with ‘AIDS wasting’, but this is quite different in terms of the effects on body composition.  Lipoatrophy specifically affects the fat tissue just under the skin surface (subcutaneous fat), leading to fat loss that is particularly noticeable over the legs, buttocks and face.  It is also notable that the lean body mass (i.e. muscle tissue predominantly) is unaffected in the case of lipoatrophy, and indeed muscle mass often improves in the presence of lipoatrophy.   On the other hand, AIDS wasting associated with untreated HIV predominantly affects lean body mass while having less of an effect on fat tissue.  The only exception here is that women with advanced HIV disease tend to lose fat as well as muscle, although again this has different characteristics. Loss of fat in AIDS wasting in women tends to be generalised (i.e. the same all over the body) as with any weight loss, while part of the reason that lipoatrophy is so noticeable in both men and women is the way in which fat loss is so ‘unevenly spread’ over the body.  For women in particular, the preferential loss of fat over the legs and buttocks associate with lipoatrophy is quite unusual.      

2-      Your lipoatrophy data on AZT shows about half the adipocyte (fat cell) depletion that is caused by d4T. Do you think that depletion of fat cells and mitochondrial DNA/function is enough to warrant industrialized countries to minimize the use of AZT for first line therapy?

This is a very interesting question, and one where there is no definitive answer yet.  The adipocyte depletion findings tell some of the story, although the clinical data are probably more important in showing how significant the effect of AZT is in terms of lipoatrophy risk.  Overall, the severity of fat loss and the risk of clinical lipoatrophy is approximately halved with zidovudine treatment compared to stavudine.  This means that in ball park terms, the risk of developing noticeable fat loss is 15-20% after 3 to 5 years of zidovudine treatment.  My own view (and again there is no consensus opinion available as yet) is that the impact of zidovudine treatment is not sufficient to minimize its use for first line therapy in industrialized countries; for a number of reasons:

·       The fat loss associated with zidovudine treatment tends to be fairly slowly progressive, typically beginning after the first year of treatment with the greatest risk of fat loss between 12-36 months.  In this instance, if those taking AZT (and those clinicians treating them) are aware of the risk of lipoatrophy and actively monitor for early signs (i.e. fat loss that particularly affects the legs, buttocks and/or face, and which is often not associated with any loss of weight), then treatment can be altered if and when this complication develops.  We know from the results of ‘NRTI switching’ studies involving the use of abacavir or tenofovir that fat loss is at least halted, and often improves, when the NRTI drugs are changed.

·      There are host and disease factors that also contribute to the risk of lipoatrophy when AZT or d4T are used (although, as stated above, these risk factors only operate when these drugs are used).  Therefore, the risk of lipoatrophy with AZT treatment is likely to be substantially reduced in those who are younger than 35 years of age, who are of non-white racial origin, and who start treatment when the CD4+ T cell count is greater than 100-200.

·    Finally, I think that part of the reason that AZT has remained in continuous clinical use since 1987 is that it has a favourable resistance profile in terms of its interaction with other NRTI drugs (see below).  The available data for newer backbone NRTI drugs such as tenofovir and abacavir is certainly very promising, but there are still some questions regarding both their long-term effectiveness and (to a lesser extent) the potential for tenofovir to cause renal and/or bone toxicity.   

3-      For those who want to start or remain in a non protease inhibitor combo, AZT seems to have a protective role in the selection for K65R and L74V/I in all nucleoside combos. How can those patients or doctors balance this fact with the potential lipoatrophy effects of AZT?

Again, a very interesting question.  I think it is fair to say that any triple NRTI drug regimen needs to include AZT to have a good chance of success, given the poor outcomes that have been associated with NRTI combinations such as tenofovir/abacavir/lamivudine or tenofovir/didanosine/lamivudine (very poor efficacy), or stavudine/didanosine/abacavir (poor efficacy and high toxicity) [reviewed in 1].  In these regimens, it appears that these drugs all tend to favour the emergence of a similar pattern of resistance mutations, so that there is very little barrier to the emergence of K65R or L74V/I.  AZT appears to counteract this effect, as it pulls in another direction, actually becoming more potent when these resistance mutations start to emerge.  This means that the virus has more difficulty becoming broadly resistant to both AZT and the other NRTIs (most commonly lamivudine and abacavir) within the NRTI combination.   As stated above, I think the risk of lipoatrophy associated with AZT can be managed in a rational way that minimises the chances of developing problematic fat loss, and in this particular case (when triple NRTI therapy is desired) there really is no effective alternative drug at present.

4-      Do you think the move in international and US guidelines for delayed treatment at lower CD4 counts will increase the incidence/prevalence of lipodystrophy in the HIV population?

I think there is strong evidence that delaying treatment until CD4+ T cell counts fall below 200 increases the risk of a number of drug-related toxicities, including lipoatrophy (if using d4T or AZT) and neuropathy (which can be associated with HIV itself as well as the use of stavudine, didanosine or zalcitabine) [reviewed in 2].   There is also a concern that low HDL-cholesterol levels associated with more advanced HIV disease may predispose patients to metabolic complications and the potential for a greater risk of cardiovascular disease [3].  I would argue that treatment should be initiated at higher CD4+ counts (i.e. 200-350) and should be focused on:

·       Assessing each individual case on its merits.  This means taking into account the patients characteristics and finding the best match in terms of HIV therapy.  These considerations may include the toxicity profiles of individual HIV drugs, as well as the tolerability of the HAART regimen.  The main goal is to provide the best possible chance of achieving 100% adherence to therapy. 

·    Assessing and monitoring those side-effects that are specifically associated with HIV drugs that are being used, so that these complications can be picked up early and managed appropriately.       

5-      The TARHEEL study results seem to point to the intriguing fact that even though mitochondrial DNA (mtDNA) levels rebounded after d4T therapy was discontinued, mitochondrial function did not recover. Do you think that there may be some permanent mitochondrial damage even after patients switch from d4T or AZT to non-thymidines?

I think the mitochondrial toxicity at a cellular level is reversible, as it is likely that the toxic of these drugs is mediated specifically by their effects on mitochondrial DNA depletion.  The more worrying problem is that severe lipoatrophy represents a profound loss of adipocytes (fat storing cells) within the fat tissue through cell death (apoptosis).  The TARHEEL study showed very nicely that you can ‘turn off this process of cell death by switching from d4T to a non-thymidine NRTI (i.e. far fewer cells are killed), but you are then left with the problem of having to replace the cells that have been lost.  While the non-thymidine NRTIs are obviously not toxic to fat tissue, they do not actively encourage new cells to grow, and treatments that may be anticipated to help this process of regeneration (such as rosiglitazone) have not performed well to date.  This problem is further complicated by the fact that lipoatrophic fat tissue contains a large number of macrophages, inflammatory cells that are probably there to mop up the adipocytes and their stored fat after cell death, and these may also inhibit the growth and development of new fat cells.      

6-      What is your opinion about the use of micronutrients (carnitine, coenzyme Q-10, thiamine, riboflavin) or the use of Uridine to reverse or prevent loss or mitochondrial DNA or function in the presence of thymide analogs?

With regard to the micronutrients you mention here, there is no evidence that they improve any clinical outcomes if used as a preventive treatment.  They have been used in the management of lactic acidosis (usually in an intensive care setting) although because these events are so rare the benefits are not really known.  Uridine treatment (in the form of a sugar cane extract called Mitocnol or Nucleomaxx’) has shown a lot of promise as a preventive treatment that may limit the toxicity associated with either stavudine or zidovudine without compromising the effectiveness of these drugs against HIV, but these results have been obtained primarily from the laboratory. Clinical experience with this extract is minimal at present and the cost of treatment is ~$100/month.  I'm sure more information will be available in the next year or so, which will be watched with interest.      

7-      We have seen several studies that show improvement in limb fat after switching patients from AZT or d4T to abacavir or tenofovir. Unfortunately, no one has really been able to quantify facial fat in those studies. Do you think that patients with moderate to severe facial wasting may see improvements after this switch? Some of your data show loss of fat cells due to macrophage activation. Do you think people may not have enough fat cells for facial lipoatrophy reversal?

This is an important area, but one where it has been difficult to obtain good data.  Facial lipoatrophy is obviously one of the most stigmatizing aspects of lipodystrophy, and this is an area where people really want to see improvement following NRTI switching.  We do see improved facial appearance associated with NRTI switching, although in general the more severe the initial lipoatrophy (prior to switching) the more limited the improvement.  This is a frustrating aspect of the syndrome, as it is a case of first affected, last to improve.  This means that less affected areas (such as the arms and trunk) tend to improve before more badly affected areas such as the face and legs.  Also, because the process of regrowing populations of fat cells seems to be slow, improvements happen over years rather than months. 

8-      What is your personal opinion about the fact that AZT and d4T are still becoming the most popular HIV drugs for the treatment of HIV people in the developing world?

My own opinion is that we need to put this issue on the agenda and keep it there particularly in the case of stavudine, where there is a substantial concern about toxicity issues.  There is a rationale that stavudine may be better tolerated in non-white populations and certainly this is an anecdotal opinion that is expressed by clinicians who look after mainly African American patients.  However, the potential toxicity of these drugs needs to be assessed carefully and quickly in the developing world, before the development of severe and widespread complications. We have already seen the burden of disease associated with severe lipoatrophy in our own communities this history should not be reproduced in developing countries.    

9-      Besides lipoatrophy, what other long term health implications do lower mitochondrial DNA and function mean to someone with HIV?

In truth, probably very few.  The effects of NRTI drugs on mitochondrial function appear to be very tissue-specific, so in the case of lipoatrophy it is very likely that the damage is limited specifically to fat tissue.  For example, it is notable that stavudine treatment which has been consistently associated with severe mitochondrial DNA depletion in adipocytes has no significant effects on mitochondrial DNA in blood cells.  Also, the mitochondrial toxicity associated with NRTI appears to be readily reversible, in the sense that mitochondrial DNA depletion goes away quickly after ceasing/switching NRTI therapy.  

10-  Will we ever have data to show whether or not ddI is implicated in lipoatrophy?

Some historical data exists suggesting that ddI treatment is not associated with lipoatrophy.  For example, an early study of dual NRTI therapy by Thierry Saint-Marc (published in 1999) included a number of patients receiving didanosine in both stavudine (d4T/ddI = 13/27, 48%) and zidovudine treatment groups (AZT/ddI = 13/16, 81%) that were well-matched for NRTI therapy duration.  In this study, use of stavudine remained the most significant risk factor for lipoatrophy (relative risk 1.95 compared with zidovudine), while no significant didanosine effect could be demonstrated [4].  More recently, results from the FTC-301A study also suggest that the once-daily NRTI drug emtricitabine (FTC) compares favourably with stavudine (each combined with ddI-EC and efavirenz) in terms of lipoatrophy risk over 72 weeks (n=571), while maintaining equivalent efficacy and improved overall tolerability. Average loss of fat was noted only in the stavudine group, despite the fact that ddI was used in both study arms [5].  More long-term data are awaited in this study.

11-  In your experience, does tenofovir have the same or different benefits when it comes to lipoatrophy reversal/prevention as abacavir? How about when it comes to lipids?

We have observed the same non-toxic effects on adipocytes mitochondrial DNA levels for these drugs, and the study data certainly suggest that tenofovir and abacavir are not associated with risk of lipoatrophy (both with an incidence of <3% over 3 years).  In this respect, neither drug will have a particular advantage. With regard to lipids, the lipid lowering effect of NRTI switching appears to basically represent the effect of removing stavudine from the HAART regimen (in NRTI switching strategies) or of removing PI drugs such as indinavir, rather than any special attribute of tenofovir or abacavir.  There was some attempt to differentiate the effects of abacavir and tenofovir on lipid/lipoatrophy outcomes in presentations at this years CROI, but I think these will come to nothing once other confounding factors are taken into account.  From the lipodystrophy point of view, including both metabolic and lipoatrophy outcomes, these are both good drugs. 

 12- What makes subcutaneous fat so different from visceral or dorsocervical fat? Why do  nucleoside analogs not affect visceral fat? Why does insulin resistance seem to expand visceral and dorsocervical fat but not subcutaneous fat?  

Probably the best way to conceive of the difference between subcutaneous fat and these other fat depots is that subcutaneous fat is the ideal storage site for dietary fat, while visceral fat tends to function as an overflow system if the fat-storing capacity of the subcutaneous fat tissue is exceeded.

This means that subcutaneous fat responds very effectively to the insulin stimulus that is associated with eating a meal. What happens in this transition from a fasting to a  fed state, therefore, is that:

·        fat tissue stops breaking down its stores of triglycerides, (where it has been used as an energy source during a period of fasting);

·        fat tissue starts to take up dietary fatty acids very efficiently (so that it stores energy in the form of triglyceride for later use while the dietary sugars and protein provide an immediate source of metabolic fuel). Overall, about 50% of a dietary intake of fat gets stored in this manner.

The whole idea of this process is that fat stores are created while there is food around, so that there is an energy source available for a period of fasting (eg. overnight for those who dont have late-night snacks!). As you can imagine, this is a system that has evolved over thousands of years when fast food hadn't been invented and the next meal wasn't always guaranteed!

In this context, visceral fat is different in that it doesn't respond to insulin so strongly which means that it doesn't generally compete with subcutaneous fat tissue for the storage of dietary fat. It is also much more labile, in that fatty acids are also released back into the circulation much more readily from visceral fat than from subcutaneous fat.  Its purpose is probably to create a short-term store of fat that can be used again quickly, without running the risk of letting excess fatty acids build up in tissues such as muscle and liver where they can be quite damaging. So from a metabolic point of view, there are a couple of important points to make here. One is that you can create excess visceral fat by eating more fat than your subcutaneous stores can cope with.  The second is that insulin resistance which means that tissues (including subcutaneous fat but also liver and muscle) don't react to the presence of insulin appropriately reduces the ability of subcutaneous fat to store fat in the most efficient way.  This leads to the accumulation of fatty acids in all the wrong places (muscle, liver) and also creates a reservoir of fatty acids (from visceral fat) that is released at all the wrong times (eg. even when you've just eaten and there is already plenty of metabolic fuel available). How does this relate to lipodystrophy?

1.      Visceral fat accumulation is a part of the ‘Metabolic Syndrome that includes insulin resistance and dyslipidemia, and these three elements cluster together quite strongly;

2.      Excessive dietary intake of saturated fats and sugars contributes to the development of visceral obesity by exceeding the capacity of the subcutaneous fat to store dietary fat in an appropriate way, and lack of exercise also leads to fat not being burned as a source of energy.  This means that you don't have to have HIV infection and/or PI therapy to get these problems and indeed ~30% of US adults are affected by this Metabolic Syndrome. 

3.      Once visceral obesity is established it makes it harder to recover from insulin resistance, as there is always a source of fat that must also be burned along with dietary fat before the system can go back to efficient functioning.

4.      One of the least understood areas is whether having lipoatrophy also contributes to the risk of insulin resistance and visceral obesity. This would make some sense, as having less and/or poorly functioning subcutaneous fat would be likely to make it easier to overload the capacity of this organ to store fat.  Some recent data from the Netherlands [van Wijk JP, et al J Clin Endocrinol Metab. 2005 Mar 22; [Epub ahead of print] support this possibility, indicating that more severe lipoatrophy increases the risk of insulin resistance. I think this is an example of how we need to think carefully about how to look after the health of those who are affected by severe lipoatrophy into the future.

Getting back to the original question, it is not really known why stavudine and zidovudine don't affect visceral fat in the way that they cause lipoatrophy.  One explanation may be that visceral fat is intrinsically more resistant to mitochondrial toxicity, because (1) it doesn't rely so much on energy-requiring processes such as triglyceride synthesis, and (2) because it expresses anti-apoptotic proteins (one is called cIAP) that make visceral fat cells less susceptible to mitochondrial toxicity and subsequent cell death.  At this stage, no one has collected fat samples from this fat depot in HIV-infected patients.   

12-   Besides serving as caloric storage and may be protection against the elements, what other function does subcutaneous fat have?

This is currently a ‘boom’ area in medical research, as it becomes increasingly recognized that subcutaneous fat actually functions as an active metabolic organ rather than as an inert storage site.  There are many examples of how this plays out, but the case of adiponectin might be a good starting point.  Adiponectin is basically a hormone that is released only from subcutaneous fat, which profoundly influences the way that fatty acid metabolism is regulated by the body as a whole. When subcutaneous fat tissue is healthy (and not affected by insulin resistance) it releases increased amounts of adiponectin into the system, which acts as a signal for the body to efficiently ‘burn’ the fat that is present in muscle and liver.  This means that adiponectin acts to protect against insulin resistance.  However, when subcutaneous fat is not functioning properly, adiponectin levels go down and this then becomes part of the problem of insulin resistance – fat is allowed to build up in the wrong places and is not efficiently burned.   There is a lot more to this story, but to summarise it is certainly true to say that subcutaneous fat is an integral player in metabolism generally – and is likely to be just as important to ‘metabolic health’ as muscle or liver. 


1.      Arribas JR. The rise and fall of triple nucleoside reverse transcriptase inhibitor (NRTI) regimens. J Antimicrob Chemother. 2004;54:587-92.2.      Keswani SC, Pardo CA, Cherry CL, Hoke A, McArthur JC. HIV-associated sensory neuropathies. AIDS. 2002;16:2105-17.3.      El-Sadr WM, Mullin CM, Carr A, Gibert C, Rappoport C, Visnegarwala F, Grunfeld C, Raghavan SS. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med. 2005;6:114-21.4.      Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS. 1999;13:1659-67. 5.      Saag MS, Cahn P, Raffi F, Wolff M, Pearce D, Molina JM, Powderly W, Shaw AL, Mondou E, Hinkle J, Borroto-Esoda K, Quinn JB, Barry DW, Rousseau F; FTC-301A Study Team. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial. JAMA. 2004;292:180-9.


Interview with Dr. Lemperle about facial implants

By Nelson Vergel

I met Dr. Gottfried Lemperle in San Diego for breakfast a month ago. He turned out to be a very pleasant and passionate guy who knows a great amount of information about facial implants. He is currently a cosmetic surgery professor at UC- SD medical school. He moved to the US 3 years ago from Germany, where he holds patents with his son on microspheres for facial implants. These are his answers to my questions:


For facial lipoatrophy, there are solid and injectable implants commercially available. The solid ones from polymerized silicone, Teflon, hydroxyapatite, or polyethylene can be cut to suitable shapes and implanted on the malar bone, maxillary sinus, and the mandibular arch. The center of the cheek, the atrophied Bichat's fat pad can be augmented with an oval shaped implant from soft silicone (1), which was first choice before the era of permanent soft tissue fillers.
The ideal injectable dermal filler substance must be biocompatible and safe, stable at the implantation site, retain its volume and remain soft and pliable, should not dislocate by gravity, and evoke minimal foreign body reaction (2).


The potential risks of temporary filler substances, such as collagen, hyaluronic acids, polylactic acid or PMA beads, are fast absorption within 3 to 6 months, allergic reactions and - not yet understood - late granuloma formation.
Permanent filler substances, such as silicone fluid or gel, polyacrylamides, silicone particles, or PMMA microspheres, carry the risk of technical mistakes during implantation, allergic reactions, dislocation by muscle movement or gravity, and late granuloma formation.


Dislocated implants or lumps can be diminished and softened effectively by intralesional corticosteroid (Kenalog) injections (3). They inhibit fibroblasts from producing collagen fibers, thereby reducing the volume of the encapsulating host tissue by half. The rather rare granulomas (1 in 10,000), which are an ongoing foreign body reaction, can also be reduced to its former size by corticosteroids. Since every patient reacts differently to these drugs, which may cause temporary atrophy, when injected into the subcutaneous fat, these strictly intralesional injections have to be repeated in 3-weeks intervals. Larger depositions of silicone gel or polyacrylamides can be reduced by suction. Surgical excisions are never indicated !


In rats, artificial substances such as solid polymers can cause sarcoma formation on smooth surfaces and edges (Oppenheimer effect). This effect, however, could never be demonstrated with the same substances injected in powder form, e.g. as microparticles or microspheres. In humans, no malignant tumor formation has been reported on substances, which have been used for more than 50 years, such as paraffin, silicone, or PMMA-bone cement.


Since 20 years, I have a personal experience with all injectable substances. I have injected all of them into the skin of my left forearm to control persistence and histology. There is no question: the risks of lumpiness and dislocation are less in temporary fillers since both will be absorbed within a few months. On the other hand, the costs of repeating these treatments every 6 months are certainly much higher than one to three treatments with a permanent filler.
Silicone fluid can be effective and durable, however, dislocation by gravity in patients with loose connective tissue, and late granuloma formation in some patients have banned its use in most countries.
Polyacrylamides appear to be very biocompatible and do not cause the formation of a capsule at all. Therefore, the deposit can dislocate by gravity in certain patients and have to be removed by suction.
For me, tiny microspheres from any non-absorbable polymer are the material of choice for tissue augmentation today. Their smooth surface allows encapsulation instead of rejection, and permanent fixation at the location, where they were injected.


Since two years, we are trying to find a substance, which will have a semi-permanent effect of about 2 years in the human tissue. All efforts to change the formulation of polylactic acids have failed, so far. NewFill® microspheres are absorbed within 3 - 6 months and therefore not worthy for the treatment of a lasting condition such as facial lipoatrophy.


Artecoll has been used in Europe and ex-US countries for over ten years in more than 200,000 patients worldwide. Each of the 6 million microspheres is encapsulated with the body's own connective tissue, which makes up 80 % of the final implant. Until 1994, the microspheres had tiny PMMA particles attached, which were the cause of granuloma formation in some patients. These cases are still mentioned on meetings but are history, fortunately. The clinical trials in the US showed its lasting effectiveness without any side effects worth mentioning. The FDA reveals the application of approval and will make its decision by the end of 2002.
To my 12-year experience with Artecoll, a medium lipoatrophy needs at least 5 cc of filler material on each side to be treated successfully. Therefore, one or even 2 cc injected too deeply will easily give the impression of disappearance to the patient. Especially in an atrophic skin, one has to be very carefully to deposit Artecoll deep dermally and not into the residual subcutaneous fat ! Your friend may have got a small amount injected.


Polyacrylamides have been used extensively in Ukraine for 20 years, however, no statistical data are available. Histologically, it causes almost no reaction or capsule formation (2) and shows similarities to inert fluid silicone. Since the patent expired recently, at least 7 European companies produce filler substances from this material. A high health official in China, however, told me some months ago that polyacrylamides (Interfall®) will be prohibited soon because of a high incidence of enlarged lymphnodes, dislocation by gravity, and granuloma formation in Chinese patients.


Since more than 20 years, there is only one product approved for soft tissue augmentation in the US, and that is bovine collagen (Zyderm® and Zyplast®). Hyaluronic acid products (Restylane® and Hylaform®) are in clinical trials and may be approved in 2003. Both are, however, not longer lasting than collagen, have similar side effects and can cause late granulomas like collagen. Polylactic acid microspheres (NewFill®) are in clinical trials for facial lipoatrophy but are not longer lasting than collagen, too.
Scientifically, Artecoll® consisting of microspheres sieved from bone cement (polymethylmethacrylate) and suspended in collagen is the best and longest proven materials in aesthetic surgery, and therefore my first choice for the treatment of wrinkles and facial lipoatrophy. I would switch tomorrow to a better injectable material, if there would be one.


The HIV community should approach the companies of soft tissue fillers and ask for clinical trials especially with facial lipodystrophy patients. Later on, these companies should provide the material at their lowest price exclusively for HIV patients. Since side effects of drugs are real diseases, the FDA should categorize these trials as urgent and renounce their usual long way of approval process. The HMO's should recognize F.L. as a disease and discuss a certain amount for the physician's reimbursement. If this does not work out soon, it's common practice among pharmaceutical companies to reimburse patients for the treatment of side effects caused by their drugs.


The fears about silicone gel being immunogenic, which have been launched in the early nineties by some focused physicians, lawyers, and breast implant patients, have been proven by many rheumatologists and epidemiologists to be unfounded. Soon, gel filled breast implants will be on the US market again. The only case I know of as an expert witness, which tries to relate multiple sclerosis to injected fluid silicone, is still not settled in London.


I am well aware of the importance the stigma of facial lipoatrophy means to its bearer. There is an easy applicable and safe way of leveling this deformity in 3 to 5 ambulatory sessions to its former appearance. The price per syringe is rather high and must be reduced effectively to meet the needs of these real patients. Furthermore, HMOs must realize the effect of such a treatment on the working capacity of a whole important community.

1. Hasse FM, Lemperle G: Resection and augmentation of Bichat's fat pad in facial contouring. Europ J Plast Surg 17: 239, 1994
2. Lemperle G, Romano JJ, Busso M: Soft tissue augmentation with Artecoll: 10-year history, indications, technique, and potential side effects. Dermatol. Surg.28:, 2002
3. Lemperle G, Morhenn VB, Pestonjamasp V, Charrier U, Gallo RL.
Histology, persistence, and migration studies of various injectable filler substances for tissue augmentation. Plast Reconstr Surg 112:, 2003

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