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New-Fill: A Brighton Experience
One of the most distressing side effects of HAART is facial lipoatrophy, which is estimated to occur in 13-48% 1,2,3,of patients, depending on their antiretroviral regimen. Loss of subcutaneous adipose tissue, particularly around the cheeks and temples, leads to characteristic changes in facial appearance. Many individuals are concerned these changes are recognised by others, who may then suspect they are HIV positive. One man described "a transient flicker of realisation" crossing the faces of people he meets. Many people feel their choice regarding disclosure is removed, that their confidentiality has been breached, and they describe feeling stigmatised in certain surroundings. Some complain of low mood and may withdraw from social events. Others describe the dichotomy of feeling well, of having good blood-test results, but being told they look tired, older or gaunt. Some people say by being repeatedly told they look unwell, they begin to believe it, resulting in a pessimistic outlook on their overall health. Others say their facial appearances resemble those of friends with advanced HIV who have died and feel constantly reminded of their own mortality. Negative feelings towards antiviral treatment may develop and in extreme circumstances patients may stop therapy against specialist advice.
What is New-Fill?
Polylactic acid has been used in medicine and surgery for over 30 years for a variety of indications such as orthopaedic implants, tissue reconstruction and resorbable sutures. It has an established safety record and unlike collagen is immunologically inactive and can therefore be used immediately without the need for preliminary testing. To date, no allergic reactions have been reported. New-Fill (polylactic acid) has been used in cosmetic surgery for the last ten years (including preapproval clinical studies), and for HIV-related facial lipoatrophy since 1999. It is injected as a concentrated suspension into the deep skin layer where it stimulates the cells that naturally produce collagen. Examinations of biopsies have shown persistence of New-Fill micro-particles at 18 months which may partly explain its durability. Sustained treatment effects are thought to last from between one and two years, a finding recently confirmed by follow-up data from the VEGA trial4. Investigators in this French study have found that the highly statistically significant improvements in skin thickness were sustained at two years with accompanying improvements in facial appearance. This compares to the use of other fillers, such as hyaluronic acid or collagen injections, where further treatment is usually required every four to six months.
New-Fill comes to Brighton
After October 2000, following the first presentation of the Vega trial in Athens, we had increasing numbers of enquiries from our patient group regarding availability of New-Fill locally. In early 2001 we approached our local plastic surgeon with a view to setting up regular clinics. As it transpired, he was unable to commit to fixed sessions and didn’t routinely perform the technique. The possibility of a plastics nurse training to carry out injections was considered but at the time we were unable to fund on going sessions from within the HIV department. Nevertheless we included New-Fill as a cost pressure in the predicted drug budget for 2001/2002 and it was later approved by the formulary committee. New-Fill is actually registered as a medical device rather than a drug; however we felt the pharmacy department, who are familiar with new agents in the field of HIV, were well placed for monitoring adverse events. We therefore order and dispense New-Fill through pharmacy. Following consultation with the Medical Defence Union, who advised, providing practice was within the NHS, no extra cover was required; I started appropriate training by the representative from MediPhill, Mandy Cameron, in March 2002. This comprised a period of observation followed by several training clinics where Mandy was available to ensure correct technique and offer helpful advice.
The process demystified
For referral to the clinic patients must be on HAART, or have taken it in the past. There also needs to be a consensus between the clinic doctor and the patient that New-Fill could be beneficial. In order to prioritise cases, physical appearance and psychological impact scores (mild, moderate or severe) are assessed by the clinic doctor. These have shown that 51% of cases have been graded with severe physical changes and 85% recording moderate or severe psychological impact. Prior to the session the procedure is clearly explained, written consent is obtained and photographs are taken for clinic records. These are repeated four weeks after the final injections. Patients are advised in their appointment letter to take oral painkillers before leaving home. The reaction to facial injections is tremendously variable, although they are usually well tolerated, particularly with repeated local application of ice. The New-Fill - which is mixed with a total of 4-5 ml. of local anaesthetic and water - often requires up to 40 small injections into the affected areas on each side to ensure an even distribution. The length of the procedure is usually 15-20 minutes. Of the 75 cases treated so far, a couple have felt faint during the procedure and needed to lay flat and a further patient required diazepam for a panic attack. Patients are given the option of terminating the treatment at any stage and are shown results at the half-way point if they choose to look. Although some have had doubts during the procedure, they have all continued after observing the results, and have always returned for subsequent sessions. Post-treatment massage is essential for a smooth finish and patients are shown how to massage the treated area, which they are encouraged to do for a minimum of 20 minutes each day until review. This breaks down any subcutaneous nodules, which would otherwise leave a lumpy appearance. Two patients who experienced significant weight loss for unrelated reasons, reported palpable but non-visible subcutaneous micro-nodules, which resolved when they regained weight. One of these noted a transient "granular" appearance of his temples during this period of time. There have been no serious side effects although three patients reported moderate bruising, which resolved after five to seven days.
Facts and figures
Since the New-Fill clinic started there have been 75 referrals, 73 male and all Caucasian. Of the 75, the median age was 42 years (range 28-73 years) and the average time since HIV diagnosis nine years (range 2 -19 years). The majority of patients have been on therapy for many years with good CD4 counts, and excellent general health. Most (96%) had taken stavudine (d4T), although many had switched this agent, with over three-quarters citing lipodystrophy as the reason. The average length of time cases had been on stavudine was four-and-a-half years, with a maximum of just over six years.
For those patients who have completed treatment the average number of sessions has been four (range 2-8), with 20% requiring single top-up injections an average of seven months later (range 2-15 months). Two patients have required several top-up injections. Most patients so far, however, have not required any further intervention at an average follow-up of one year. The number of referrals to the clinic has declined over the last six to eight months, which may partly represent declining exposure to drugs that are associated with lipoatrophy, but also reflects clearance of the "backlog".
High satisfaction levels
It's difficult to describe the depth and intensity of feeling I've witnessed following treatment sessions when patients see themselves in the mirror. I used to follow people into the room to assess their reaction to the treatment, but felt I was intruding on a private moment. There’s often a mixture of amazement, disbelief, recognition and relief. Many patients are overcome with emotion. People describe being able to "face the world again", and not to have to "keep their heads down" as they walk down the street. One patient said he'd "been given his life back". Another didn't have to continue telling his mother he was vegetarian, his excuse for losing weight and looking thinner. Others have started going out more, getting new jobs, starting new relationships and just "getting back to normal". One had become introverted and irritable in his job as a teacher, which had been noted by his boss. After treatment he was "like a different person" taking the kids on field trips, sharing a joke and performing better at work. The same patient told me before the treatment he regularly avoided meeting old friends in case they looked at his face and realised he had HIV. One of the female patients was looking forward to not being called names by the kids in her street and not being repeatedly mistaken for a man. These comments are born out by simple satisfaction scores collected before and after treatment. Patients are asked, ‘How do you feel about your appearance?’ Before treatment only 1.8% of patients recorded "very happy". This increased to 93% after treatment.
Restarting HAART
Three of the patients treated in Brighton had previously stopped their antiretroviral therapy as a direct consequence of their altered facial appearance, two of whom had rapidly falling CD4 counts and severe immunosuppression. Following New-Fill treatment all three were able to re-start on HAART and achieved undetectable virus, avoiding further disease progression. However, the majority of patients reported that their facial lipoatrophy had no effect on their adherence (84%), with 95% of those on therapy having undetectable viral loads.
Advice for other clinics
Unfortunately the Brighton clinic is only funded to provide New-Fill to patients registered at the clinic, although we feel strongly it should be available to all individuals with psychologically distressing facial lipoatrophy across the UK. Although the minimum number of referrals needed to set-up and sustain a service is difficult to define, by working through clinical networks, centres may find funding more easy to secure. Furthermore, clinicians working across several centres would have a greater opportunity to maintain clinical skills.
In conclusion, facial lipoatrophy is a distressing side effect of HAART which can have a negative impact on level of confidence, well-being and the quality of life of people living with HIV. New-Fill injections to correct lipoatrophy are well tolerated, simple to administer and relatively free from complications. As one patient put it, for him "it has been the most life-changing development since the introduction of protease inhibitors", and in our experience it has certainly provided an exciting and highly significant step forward.
References
1. Joly V et al . Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial. AIDS 16(18):2447-54, 2002.
2. Lichtenstein KA et al. Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients. JAIDS 32(1):48-56, 2003.
3. Worm D et al. Clinical lipoatrophy in HIV-1 patients on HAART is not associated with increased abdominal girth, hyperlipidaemia or glucose intolerance. HIV Med 3(4):239-46, 2002
4. Valantin MA et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS 17(17):2471-7, 2003.