Current estimates suggest that approximately 30 to 40% of people taking antiretroviral therapy will develop some form of facial wasting, a component of the lipodystrophy syndrome, and that facial fat loss tends to occur quite rapidly, often within three months. How to prevent or reverse facial wasting is not known at present. Consequently, there has been a move towards the use of reconstructive or surgical procedures intended to fill-out sunken cheeks in people with facial wasting.

There are several experimental procedures being used to reduce the visible consequences of facial fat loss. These include: polylactic acid or New Fill; polymethyl methylcrylate (PMMA); polyvinyl / polyacramide gel (Evolution) and fat transfer injections.

Treatment advocates have urged that these interventions should not be described as cosmetic, but as reconstructive surgery, because they are needed to repair the effects of HIV treatment and the disease process. Arguments for the funding of reconstructive surgery are likely to be taken more seriously when the procedures stop being described as cosmetic.

As described in more detail below, several observational studies have reported the benefits of these techniques, although the long-term risks and benefits of these procedures in people with HIV are unknown. It should also be noted that all the studies mentioned here drew upon the expertise and work of highly experienced cosmetic surgeons.

Access to cosmetic procedures for HAART-related facial wasting through the National Health Service is currently limited, although some UK HIV treatment centres are negotiating with health purchasers to provide some procedures (see below for details). Self-funded cosmetic surgery may also be an option.

Polylactic acid (New Fill or Sculptra)

Polylactic acid is a preparation already used in cosmetic surgery as treatment for fine lines, wrinkles and furrows. Also known by the brand name New Fill, or Sculptra in the United States, it works by stimulating the growth of collagen, a structural component of the skin and other body tissues, and the development of a thicker layer of skin which fills out the wasted regions of the cheeks.

Polylactic acid differs from silicon and collagen implants in that it isnt immunologically active, thus avoiding any prospect of allergic or inflammatory response. In addition, unlike silicon implants, it is broken down and absorbed by the body.

French researchers have reported on three studies which test the usefulness of polylactic acid in relieving the facial fat wasting seen in people with HIV. In the first study, on average, four injections of polylactic acid were given to 33 HIV-positive men with facial wasting. All the patients had some degree of improvement, but the facial fat compartment was not significantly restored. Following this cosmetic procedure, skin thickness had increased from an average of 3.1mm to 8.15mm - a highly significant improvement. Seven patients had their normal facial appearance restored by the third injection (Amard 2000).

A second study, the Vega trial, enrolled 50 patients, who received four or five polylactic acid injections. All had been taking HAART for at least three years, had a viral load of less than 5,000 copies and severe facial wasting. At month two, the median increase in skin thickness was 8.1mm, and by month six this had increased to 9.5mm. By week 72 48% of patients had a total cutaneous thickness greater than 10mm. The reduction in facial atrophy could be noticed in most of the patients as soon as the second injection, and improved further with subsequent injections. Improved quality-of-life was reported by patients in this study (Aubron-Olivier 2001). The physical improvement was sustained in 42 of 50 patients who had completed 96 weeks of follow-up, with a median cutaneous thickness of 6.5mm (Valatin 2003).

In a third study, 40 patients received at least two injections of polylactic acid; six months after the end of treatment the average increase in dermal thickness was 2.8mm (average of both cheeks). Although no difference in quality of life score was recorded between baseline and six months after the end of treatment, patient rating of their satisfaction with their lipoatrophy was significantly improved (from 3.3 to 7.6, p<0.0001). No significant adverse events were reported (Lafaurie 2003)

A randomised study carried out in the UK has also reported promising results. In this study, thirty individuals were randomised to receive either immediate injections of polylactic acid (New Fill) at weeks 0, 2 and 4, or deferred treatment beginning at week 12. The study was designed to show whether PLA treatment resulted in improvement compared with a control group, and to determine if the initial benefit was sustained.

After 12 weeks, patients in the Immediate Treatment group reported improvement. Patients in the Immediate Treatment group also showed a trend towards lower Anxiety scores when compared to the Deferred Treatment group at week 12; this difference was on the borderline of statistical significance (p=0.056). Depression scores fell in both groups by week 24 (from 6 at baseline to 2 (Immediate) and 3 (Deferred) by week 24. Reports from independent assessors are still awaited.

The only adverse events that delayed further treatment were one case of bruising and one case of cellulites. In both cases treatment was delayed no more than one week. No negative changes in average viral load or CD4 count occurred (Moyle 2004).

Access to polylactic acid (New Fill)

Access to treatments that can repair facial fat loss is limited currently, only a few hundred patients are receiving New Fill treatment in the UK, largely through hospitals in London, Brighton and Manchester. However, demand for private treatment is such that New Fills distributor is employing a nurse two days a week to carry out treatment for people with facial fat loss who have decided to go private at a cost of around £400 a session.

Is there any possibility that New Fill treatment will become more widely available soon? The London HIV Consortium HIV Drugs Committee is likely to recommend that New Fill treatment should be provided to all patients in London who need it, but it may not be available at every centre due to the need for staff to be trained and space to be set aside in the clinic to carry out the procedure. Instead, it is likely that patients will be referred to centres within the service network (a group of hospitals that work together to provide HIV care).

Private treatment

New Fill is obtainable in the UK through MediPhill (020 7937 2377) at approximately £1200 for four sessions. It is currently administered through MediPhills nurse practitioner, or through a Harley Street clinic experienced in providing the treatment for patients with lipoatrophy (which is much more expensive).

Polymethyl methylcrylate

PMMA is an adhesive traditionally used in hip replacement surgery which has been used in cosmetic surgery for some years in an attempt to defy the aging process. As with New Fill, PMMA is injected into the hollow of the cheeks. This product is known as Metacrill and is intended to be a permanent filler.

A Brazilian cosmetic surgeon Dr Marcio Serra conducted a study of PMMA injections in 120 HIV-positive people with facial wasting. Additional injections were required in some patients at 12-18 months, either in different areas or to restore previous injections. Results based on patient report showed this to be an effective treatment. All patients reported an improvement in their self-esteem and quality of life. No infection, inflammation, or allergic reactions were reported. For the first day after the procedure, a cold compress is required every two hours to reduce swelling.

Evolution

Polyvinyl / polyacramide gel which goes by the brand name of Evolution is has been tried as a treated for facial wasting in HIV-positive patients. An observational study of Evolution injections in 35 people with facial wasting associated with long-term antiretroviral therapy found that 33 reported the results to be good or excellent one year after the intervention. Two-thirds required two injections of Evolution. The only reported side-effect was transient, local swelling in two individuals (Del Pinto 2001).

Polyalkylimide, marketed as Bio-Alcamid by its Italian manufacturer Polymekon, is a bio-prosthetic product. It is injected into the face and forms a soft gel replacement for lost fat, and is encased in a membrane that forms after the substance is injected. Its manufacturers say that it should not degrade or move. There are no data on the use of this product to treat lipoatrophy, even though its manufacturer says that the product is recommended for treatment of lipodystrophy.

Fat transfer

Another surgical approach to facial wasting is to have ones own fat removed from one body area and injected into the hollows of the face. This is referred to as autologous fat transfer and is available through private surgeons in the United Kingdom.

An American plastic surgeon, Dr Jeffery Brande, has treated 300 people with HAART-associated facial wasting using this method. Short-term results show this to be effective, once the initial swelling has resolved. Although fat transfer may be challenging in extremely wasted HIV patients, Dr Brande asserts that fat harvesting is possible in most individuals.

An Italian group has presented results on fat transfer operations in 38 patients. Patients with severe lipoatrophy but CD4 cell counts above 100 cells/mm³ were treated; 52 week follow-up is available on 16 patients. Fat was harvested from a buffalo hump (14), the abdomen (27) or other subcutaneous fat tissue (4), and injected into the cheeks. Ultrasound showed a median increase in subcutaneous cheek fat of 5.5mm at week 24 and 3.4mm at week 52. In six cases a second fat transfer was necessary because the fat had settled asymetrically. By visual analogue scale, patient satisfaction with the facial appearance improved significantly from 23.6 to 67.6. No soft tissue infections were reported. However, four patients who received fat transfer from the buffalo hump region or abdomen suffered facial fat expansion at the same time as expansion of the fat depot from which the fat had been harvested (Guaraldi 2003). The authors did not indicate whether fat was being reabsorbed, which is a major potential drawback of fat transfer techniques.

The authors also noted that 40% of patients with lipoatrophy evaluated in the clinic did not have sufficient fat to allow fat transfer to be attempted.

Silicone-based products

Silicone is an oil derived from the mineral silicon. It can be used for filling in plastic surgery, and has acquired a poor reputation as a result of misuse over the past twenty years. However, academic cosmetic surgeons in the USA are planning studies of a product called SilSkin for treatment of facial lipoatrophy. For good results silicone must be injected in tiny quantities using hundreds of micro-injections; previous bad results have been partly the consequence of injecting larger volumes of silicone (as well as using impure products rather than medical grade silicone oil).

In a presentation at the Fourth International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, Dr Derek Jones, Associate Professor of Dermatology at UCLA, reported that liquid injectable silicone had been used for treatment of lipoatrophy in several hundred patients with few or no serious complications prior to be being banned in the early 1990s.

SilSkin is not available in the United Kingdom, and will only be available through clinical trials in the United States.

Collagen

Human or bovine collagen has been used by some plastic surgeons on small numbers of patients with lipoatrophy, but the results are transient, lasting only a few months. Collagen treatment is also very expensive in comparison with products like New Fill.

Hyaluronic gel

Hyaluronic gel is a soft-tissue filler widely used in Europe. Hyaluronic acid is a natural component of the skin, holding skin cells in place. It is widely used in cosmetic products, and a gel product has been approved in Europe. It is soon to be approved in the USA. Products include Restylane>, Perlane, Hylaform. Hyaluronic gel implants persist for around a year before the filling effect begins to dwindle.

Safety data have been reported from 406,000 patients treated in 1999 and 2000, showing an incidence of 0.04 adverse events per hundred patients treated. Usual adverse events include localised hypersensitivity and injection site reactions that did not require treatment.

UniMed, the Swedish manufacturer of Restylane is planning a Los Angeles trial of its product for the treatment of lipoatrophy.

Research into polylactic acid

Lafaurie (2002) reported on 16 HIV-infected people with facial wasting who had polylactic acid (mean injection 2.5mL per cheek, per injection) injected into their cheeks on up to 5 occasions. Volume increased by about 15mm³ and significant satisfaction was reported. There was a trend towards better quality of life. 5% reported grade 1 pain.

Amard (2000) identified 33 HIV-positive men with facial wasting who had been taking HAART for an average of 64 months. 24 had severe fat loss - defined as a thickness of less than one millimetre on the cheeks. Over a six months, polylactic acid was injected below the surface of the skin an average of four times. All the patients had some degree of improvement, but the facial fat compartment was not significantly restored. At six months the dermal (skin) thickness had increased by an average of 153%, from an average of 3.1mm to 8.15mm - a highly significant improvement. 7 patients had normal facial appearance restored by the third injection, and 6 others had a maximum improvement by the fifth injection.

Aubron-Olivier (2001) enrolled 50 patients with facial wasting onto the Vega trial. Participants received polylactic acid injections of one vial of New Fill (0.15g) in each cheek at days 0, 15, 30 and 45 with the option of a further fifth injection at day 60, if dermal thickness was less than 8mm. To be included in the trial, patients had to have used HAART for a minimum of three years, have a viral load of less than 5,000 copies and subcutaneous adipose tissue thickness less than 2mm as measured by ultrasonography. They were excluded if they had prior facial implants or were pregnant. Following the injections, patients were assessed by clinical examination, further ultrasonography and by photograph. Assessment occurred at months 3, 6, 12, 18 and 24. Prior to the first injection, the median thickness of facial adipose tissue was 0mm (range 0-2.1mm). At 2 months, the median increase in dermal thickness in all patients was 8.1mm, by 6 months this had increased to 9.5mm. The reduction in facial atrophy could be noticed in most of the patients as soon as the second injection, and improved further with subsequent injections. No patients discontinued the treatment and no serious adverse events were reported. Some mild swelling around the injection site did occur but generally resolved within 1-2 days. In 10% of patients, non-visible nodules around 3-5mm in diameter occurred after 3-6 months, but these soon resolved. The authors commented that the treatment improved quality of life since all patients reported an improvement in their sense of wellbeing, though at 6 months some patients had reported feeling worse about their appearance.

Moyle randomised 30 individuals with facial lipoatrophy to receive either immediate injections of polylactic acid (New Fill) at weeks 0, 2 and 4, or deferred treatment beginning at week 12. Assessment from photographs by six independent assessors was made at week 0, 12 and 24, and patients also made their own assessments of appearance and of depression based on a Hospital Analogue Scale. After 12 weeks patients in the Immediate Treatment group reported improvement. Patients in the Immediate Treatment group also showed a trend towards lower Anxiety scores when compared to the Deferred Treatment group at week 12; this difference was on the borderline of statistical significance (p=0.056). Depression scores fell in both groups by week 24 (from 6 at baseline to 2 (Immediate) and 3 (Deferred) by week 24. Reports from independent assessors are still awaited. The only adverse events that delayed further treatment were one case of bruising and one case of cellulites. In both cases treatment was delayed no more than one week. No negative changes in average viral load or CD4 count occurred.

Other information

See www.facialwasting.org for more details of treatments for facial wasting in the United States.

References

See References - Body fat and metabolic changes.