A range of treatments for facial lipoatrophy
Simon Collins, HIV i-Base
Very few posters or presentations concerned themselves with the clinical management of lipodystrophy and in particular with reconstructive procedure to repair facial atrophy at the 4th International Workshop on Drug Reactions and Lipodystrophy in HIV Infection.
This gap was surprising given that the first presentations on New-Fill were presented at this meeting two years ago and additional treatment and updates were also presented at last year’s meeting. As this area falls outside the regular experience of HIV clinicians, calling on new expertise, a more detailed scientific overview of the risks and benefits of the various corrective procedures would be welcomed in next year’s programme.
The level of interest from patients, and the confusion in this area, was shown at a separate community-organised meeting held on the second evening of the Workshop. Four companies presented different approaches to a capacity audience of around 130 patients, doctors and community advocates. Further details from that meeting including material provided by those companies has been posted to the organisers’ website:
One of the speakers at that meeting also provided the final talk at the Lipodystrophy Workshop and had the difficult task of summarising around 20 treatments, especially as comparative data and results from clinical studies are not available for many of these products.
Dr Jones is a clinical assistant professor at UCLA and an investigator for the SilSkin studies of a new formulation of silicone oil – and his presentation tended, not surprisngly, to show preferences for this treatment. Dr Jones works with Alistair Carruthers (‘the father of Botox’) who has also developed a lipodystrophy scale grade 1-4 to categorise HIV-related atrophy. The overview included slides showing results from each procedure but it was not possible to evaluate single cases with any degree or accuracy or critical comparison.
The four categories of procedure discussed were permanent and non-permanent FDA-approved procedures, and permanent and non-permanent procedures that are non-FDA approved.
Non-permanent FDA-approved procedures included autologous fat transfer – although some surgeons working in this area have claimed that this can produce a lasting result. The procedure is reported as being biocompatible, predictable and safe. It requires the ability to carefully harvest fat and this can present a problem in some patients. It also requires more substantial surgery and related costs. At least one surgeon has suggested that reinjecting fibrous brown fat from a buffalo hump may contribute to more durable results – fat is otherwise usually harvested from the stomach or buttocks – and it can be frozen to be used again later for repeat and corrective administrations.
Collagen injections (products such as Fascian TM) with preserved particulate fascia derived from screened human cadavers are FDA approved as a procedure but non-permanent and its use to correct HIV lipatrophy has reported very short term effects and dissatisfaction with both the duration and cost.
Micronised alloderm (Cymetra TM) is a micronised collagen, reported as being more expensive than other collagen products with permanency of less than six months.
Alloderm is also available in non-micronised sheets that can be implanted through face-lift incision. Cost in this lecture was estimated at greater than $10,000 with limitations of surgical downtime. These grafts may become reabsorbed over time.
Bovine collagen (Collagen TM) is another FDA approved non-permanent treatment that was reported to improve mild lipoatrophy, although this was reported as rapidly reabsorbing over 3-6 months in the 100 patients receiving this treatment in Dr Jones’ practice.
Benefits for HIV-related facial atrophy from regular face-lift surgery were also limited and temporary – particularly if the underlying atrophy continues to progress – and is associated with major surgery and cost.
Permanent implants of ePTFE (Gore-tex, Softform, Ultrasoft) are ‘straw-like hollow implants’ that are threaded under the dermis in a radial distribution. They are FDA approved and have been used to treat HIV-related atrophy (Glougau, ASDS 2000).
Also mentioned in the permanent procedures was a product called SilSkin which is a high grade silicone oil that is reported not to have the problems of migration linked to silicone injections and which is being studied in an FDA approved facial atrophy study although it is not licensed for general use.
The list of non-FDA approved products largely contained products that are available and being used in other countries including in Europe. Non-permanent products include Polylactic acid and hyaluronic acid.
Of these, Polylactic acid (PLA, New-Fill) has received most attention in France and the UK where controlled clinical trials have shown generally very successful results with a high level of patient satisfaction and minimal complications to correct HIV-associated facial lipoatrophy. PLA is non-permanent being rapidly absorbed but then generates new collagen growth that appears to produce lasting results out to two years following three to six courses of initial treatment. Developed in France New-Fill has reportedly been bought by a US-based company and this may lead to controlled studies in the US.
Slides of two complications were shown of minor skin reactions including permanent nodules at the injection side and permanent purple staining of the skin in the area of the injections. In clinical practice a substantial number of patients show only a temporary response despite repeated injections (ref: Stefan Mauss).
Hyaluronic acid gel (Restylane, Perlane) is a polysaccharide component of living tissue that is identical in all species and tissue types and which is bioabsorbable. It is non-permanent and reportedly widely used in Europe. It is manufactured by Q-Med in Sweden and is undergoing FDA studies.
Polymethylmethacrylate (Metacrill, Artecoll) is a permanent injectable filler. Metacrill is used in Brazil and results from this unapproved and unlicensed product were presented by Dr Serra at the liodystrophy workshop in 2001. Artecoll is a formulation of polymethylmethacrylate suspended in bovine collagen and is currently being studied in FDA trials.
The final products listed included even sparser information as permanent treatments. Matrex (acrylate and methylacrylate spheres) and Kopolymer-E (containing polyoxiethylene-4 fatty esther) are both manufactured by Kuhra Vital in Switzerland, but no known regulatory approvals exist for any human indication, and claims of safety and efficacy are unsubstantiated by any clinical trials.
Biopolymere is a silicone product of unknown origin manufactured by Biocell Laboratories in Switzerland reportedly still being used by ‘backroom’ practitioners.
Polyalkylimide (Bio-Alcamid) is a synthetic filling agent (3% polyalkylimide, 97% water) manufactured in Italy (and available in Mexico) that is permanent but which can be removed later if necessary. Pre and post photos were reported as convincing and infections can occur but again no peer-reviewed data has been produced. Information from the Mexican clinic specialising in using this product is available at: http://www.clinicestetica.com
A study presented at the Athens meeting using Polyvinyl gel and polyacramide microspheres (Evolution) covered 35 HIV-positive patients with reported benefits, and only mild facial swelling in two patients.
This presentation clearly showed a wide range of products are currently available and being used in some degree to treat the effects of facial atrophy. However it also raised the significant concerns about lack of safety and efficacy data on many of these products and the vulnerability of patients to less than rigorously studied procedures. An inherent problem for agents used as fillers for cosmetic procedures is that they are usually used for indications not covered by health insurance companies. Because of this, manufacturers are only seeking approval as a medical device which is much easier and less expensive compared to an approval as a medication or medical therapy which would allow for health insurance cover, but needs formal controlled trials.
The list of compounds included in this short presentation was also by no means comprehensive (check out http://www.yestheyrefake.net for a list of injectable fillers used in the US for cosmetic procedures).
In the UK, the results of the Vega study in Paris and a New-Fill study at the Chelsea and Westminster Hospital have led to small numbers of people starting to access this treatment on the NHS. Many more have already accessed New-Fill privately, and the safety profile and results have been widely reported to greatly improve the quality of life for those patients. As with antiretroviral drugs, there will never be sufficient long-term data, but where a procedure has proved both safe and effective it should be available as a reconstructive procedure given that the lipoatrophy is either HIV or medication related.